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Due to low toxicity and anti-cancer activity, selenium nanoparticles have been studied to treat various cancers. In the present study, curcumin-loaded selenium-chitosan nanocomposites (CUR-Cs-SeNCs) were prepared, and their inhibitory effect on 4T1 cell line and tumor-bearing mice was reported. FTIR, XRD, EDX, AFM, and SEM analysis confirmed the successful preparation of CUR-Cs-SeNCs. The average size, polydispersity index, and zeta potential of CUR-Cs-SeNCs were 167.43 ± 6.52, 0.18 ± 0.05, and 35.62 ± 5.21 mV, respectively. The cumulative released percentage of curcumin from nanocomposites at pH 5.5 was about 1.8 times higher than at pH 7.4. Moreover, CUR-Cs-SeNCs showed a diffusion-controlled release pattern at pH 6.8 and 5.5. The in vitro cytotoxicity study on 4T1 cells revealed that CUR-Cs-SeNCs dramatically reduced cell proliferation rate compared to pure curcumin. Additionally, the in vivo study confirmed that the CUR-Cs-SeNCs were more successful in reducing the tumor volume than net CUR. More importantly, histopathological studies revealed a more substantial inhibitory effect on tumor growth and liver metastasis of CUR-Cs-SeNCs as compared to free curcumin. No significant signs of toxicity were detected in the vital organs of CUR-Cs-SeNCs-receiving animals. Therefore, considering the pH-dependent release, the improved inhibitory effect on turmeric cells, and the outstanding performance in the animal model, the CUR-Cs-SeNCs may be promising in future tumor management. [ABSTRACT FROM AUTHOR]

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098–3.97 μM (0.066–2.68 μg mL−1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells. [ABSTRACT FROM AUTHOR]

To efficiently deliver erlotinib HCl (ERL) to triple-negative breast cancer cells, dual crosslinked interpenetrating polymer network beads composed of carboxymethyl tamarind xyloglucan-grafted poly-N-isopropylacrylamide/montmorillonite nanocomposites and low-methoxyl pectin (LMP) were formulated. Incrementing the reinforcing clay in the matrices increased the size of the beads (1.29 ± 0.10 – 1.55 ± 0.28 mm) and improved their drug entrapment efficiency (DEE, 60.62 ± 1.02 – 86.73 ± 0.25%). The results of SEM analyses displayed spherical morphology of the fabricated beads. The compatibility of their constituents with ERL was ensured by infrared, thermal, and X-ray diffraction studies. Moreover, these beads exhibited temperature-sensitive swelling behavior and their molar masses between crosslinks ( M ¯ c), estimated adopting Flory–Rehner equation, were declined with temperature. Various matrices also showed sustained drug release patterns, which were best fitted with the Korsmeyer–Peppas kinetic model and the drug release was driven by Fickian diffusion- mechanism. Furthermore, the beads with the highest MMT content (F-3, 20% MMT) demonstrated pH-sensitive swelling and drug release patterns. These also conferred a faster biodegradability relative to the control scaffolds (F-1, 0% MMT) and enhanced sensitivity on MDA-MB-231 cells as compared to pure ERL. Therefore, CTX/LMP-based IPN beads could be exploited as promising drug-carriers for TNCB therapy. [ABSTRACT FROM AUTHOR]

In this study, a novel selenium@zeolitic imidazolate framework core/shell nanocomposite stabilised with alginate was used to improve the anti-tumour activity of curcumin. The developed alginate-stabilised curcumin-loaded selenium@zeolitic imidazolate framework (Alg@Cur@Se@ZIF-8) had a mean diameter of 159.6 nm and polydispersity index < 0.25. The release of curcumin from the nanocarrier at pH 5.4 was 2.69 folds as high as at pH 7.4. The bare nanoparticles showed haemolytic activity of about 12.16% at a concentration of 500 µg/mL while covering their surface with alginate reduced this value to 5.2%. By investigating cell viability, it was found that Alg@Cur@Se@ZIF-8 caused more cell death than pure curcumin. Additionally, in vivo studies showed that Alg@Cur@Se@ZIF-8 dramatically reduced tumour growth compared to free curcumin in 4T1 tumour-bearing mice. More importantly, the histological study confirmed that the developed drug delivery system successfully inhibited lung and liver metastasis while causing negligible toxicity in vital organs. Overall, due to the excellent inhibitory activity on cancerous cell lines and tumour-bearing animals, Alg@Cur@Se@ZIF-8 can be considered promising for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 μg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis. [ABSTRACT FROM AUTHOR]

Melittin (M) has attracted increasing attention for its significant antitumor effects and various immunomodulatory effects. However, various obstacles such as the short plasma half-life and adverse reactions restrict its application. This study aimed to systematically investigate the self-assembly mechanism, components of the protein corona, targeting behavior, and anti-4 T1 tumor effect of vitamin E-succinic acid-(glutamate) n /melittin nanoparticles with varying amounts of glutamic acid. Here, we present a new vitamin E-succinic acid-(glutamate) 5 (E 5), vitamin E-succinic acid-(glutamate) 10 (E 10) or vitamin E-succinic acid-(glutamate) 15 (E 15), and their co-assembly system with positively charged melittin in water. The molecular dynamics simulations demonstrated that the electrostatic energy and van der Waals force in the system decreased significantly with the increase in the amount of glutamic acid. The melittin and E 15 system exhibited the optimal stability for nanoparticle self-assembly. When nanoparticles derived from different self-assembly systems were co-incubated with plasma from patients with breast cancer, the protein corona showed heterogeneity. In vivo imaging demonstrated that an increase in the number of glutamic acid residues enhanced circulation duration and tumor-targeting effects. Both in vitro and in vivo antitumor evaluation indicated a significant increase in the antitumor effect with the addition of glutamic acid. According to our research findings, the number of glutamic acid residues plays a crucial role in the targeted delivery of melittin for immunomodulation and inhibition of 4 T1 breast cancer. Due to the self-assembly capabilities of vitamin E-succinic acid-(glutamate) n in water, these nanoparticles carry significant potential for delivering cationic peptides such as melittin. [Display omitted] • We presented E 5 , E 10 and E 15 co-assembling with positively charged melittin in water. • With the glutamic acid increasing, long retention and tumor targeted effect were enhanced. • M/E 15 absorbed high C1q subcomponent B in protein crown for long circulation effect. • The number of glutamic acid added, anti-tumor effect incerased significantly. • Our study provided a method to extend the half-life of positively charged peptides. [ABSTRACT FROM AUTHOR]

Exosomes are membrane vesicles 30–150 nm in size released by cells upon fusion of multivesicular bodies with the plasma membrane. A distinctive feature of these vesicles is the presence of the surface tetraspanins CD9, CD63, and CD81. The Rab family of small GTPases, including Rab27A and Rab27B, controls various steps in exosome release, including transport of multivesicular bodies and fusion of the multivesicular body to the plasma membrane. It is commonly accepted to date that exosomes are the main carriers of information between cells under physiological conditions, such as mammary development and lactation, and under pathological conditions, such as breast cancer. This review considers the peculiarities of exosome formation, secretion and transport, their composition and role in normal and breast cancer, as well as the prospects for using these vesicles to develop early non-invasive diagnostics and improve the effectiveness of anti-tumor therapy.

Breast cancer represents the most commonly diagnosed cancer worldwide, accounting for approximately one in eight cancers diagnosed. Despite significant advances in the diagnosis and detection of this disease, there is still a great need for more effective therapies to combat the invasive forms, especially those with a high incidence of metastasis. For that reason, bioactive molecules as peptides, including bovine lactoferricin (LfcinB), have been investigated. In this sense, there are reports that 20RRWQWR25 motif derivate from the LfcinB has shown activity against different cancer cell lines. Thus, current studies are being carried out with synthetic derivatives (linear, palindromic, dimer and tetrameric structures) that contain the 20RRWQWR25 motif in order to increase its activity against cancer cell lines by altering its hydrophobicity and net positive charge. In this regard, studies have focused on the use of LfcinB derivatives to combat breast cancer cell lines, with encouraging results. Therefore, in this mini-review, we present the state of the art regarding the activity of LfcinB and its analogs against breast cancer cell lines. [ABSTRACT FROM AUTHOR]

Radiotherapy is a mainstream modality for breast cancer treatment that employs ionizing radiation (IR) to damage tumor cell DNA and elevate ROS stress, which demonstrates multiple clinically-favorable advantages including localized treatment and low invasiveness. However, breast cancer cells may activate the p53-mediated cell cycle regulation in response to radiotherapy to repair IR-induced cellular damage and facilitate post-treatment survival. F-Box and WD Repeat Domain Containing 7 (FBXW7) is a promoter of p53 degradation and critical nexus of cell proliferation and survival events. Herein, we engineered a cooperative radio-ferroptosis-stimulatory nanomedicine through coordination-driven self-assembly between ferroptosis-inducing Fe2+ ions and FBXW7-inhibiting DNAzymes and further modification of tumor-targeting dopamine-modified hyaluronic acid (HA). The nanoassembly could be selectively internalized by breast cancer cells and disintegrated in lysosomes to release the therapeutic payload. DNAzyme readily abolishes FBXW7 expression and stabilizes phosphorylated p53 to cause irreversible G2 phase arrest for amplifying post-IR tumor cell apoptosis. Meanwhile, the p53 stabilization also inhibits the SLC7A11-cystine-GSH axis, which combines with the IR-upregulated ROS levels to amplify Fe2+-mediated ferroptotic damage. The DNAzyme-Fe-HA nanoassembly could thus systematically boost the tumor cell damaging effects of IR, presenting a simple and effective approach to augment the response of breast cancer to radiotherapy. To overcome the intrinsic radioresistance in breast cancer, we prepared co-assembly of Fe2+ and FBXW7-targeted DNAzymes and modified surface with dopamine conjugated hyaluronic acid (HA), which enabled tumor-specific FBXW7-targeted gene therapy and ferroptosis therapy in IR-treated breast cancers. The nanoassembly could be activated in acidic condition to release the therapeutic contents. Specifically, the DNAzymes could selectively degrade FBXW7 mRNA in breast cancer cells to simultaneously induce accumulation of p53 and retardation of NHEJ repair, eventually inducing irreversible cell cycle arrest to promote apoptosis. The p53 stabilization would also inhibit the SLC7A11/GSH/GPX4 axis to enhance Fe2+ mediated ferroptosis. These merits could act in a cooperative manner to induce pronounced tumor inhibitory effect, offering new approaches for tumor radiosensitization in the clinics. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Using a chemotherapeutic agent, such as doxorubicin (DOX), with a natural agent, such as silibinin (Sili), is highly valuable to minimize systemic toxicity. However, Sili and DOX face disadvantages, such as low aqueous solubility and poor bioavailability. Here, we have engineered a drug delivery cargo by decorating carboxylated graphene oxide (cGO) with an aptamer, HB5, for simultaneous delivery of DOX and Sili as a combination therapy against MCF-7 and SK-BR-3 breast cancer cells. The resulting Apt-cGO displayed a typical sheet-like nanostructure with a broad surface. The maximum entrapment efficiency was 70.42% and 84.22% for Sili and DOX, respectively. When the Apt-cGO-DOX-Sili nanocomposites were selectively taken up by breast cancer cells, the interaction between cGO and drugs was cleaved, causing releasing both Sili and DOX into the tumor cells, respectively. Compared to free drugs, Apt-cGO-DOX-Sili nanocomposites displayed higher cytotoxicity in vitro. Apt-cGO-DOX-Sili nanocomposites potentially suppressed some cancer cell survival signals. They accelerated cell apoptosis and increased Rb levels as well as reduced Akt, mTOR, NF-κB, and CDK2 levels. In conclusion, the developed Apt-cGO-DOX-Sili can be suggested as a simple and efficient drug delivery approach for breast chemotherapy.

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2−. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098–3.97 μM (0.066–2.68 μg mL−1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Breast cancer, one of the most common types of cancer worldwide, has a high degree of malignancy while lacking efficient treatments. The off‐target events frequently occurring in drug administration have been a major obstacle, which causes severe side effects to patients and reduces the therapeutic efficacy. An ideal medication should precisely target the specific site with precise control over concentration and duration. In recent years, there has been immense progress in polymer nanocarriers that demonstrate great potential in the targeted delivery. These nanocarriers are constructed from materials sensitive to a wide range of endogenous (e.g., pH, enzyme, redox) and exogenous stimuli (e.g., light, ultrasound, magnetic waves), driving cargo release to the targeted tissue or cells. Here, we elucidate the mechanism of current targeting strategies and the engineering methods to construct these targeting systems or to improve their targeting efficiency. We capture the recent progress in the targeted nanocarriers derived from polymers which span hydrogels and micelles, demonstrating their design and applications in chemo, hyperthermia, immuno, and gene therapies. [ABSTRACT FROM AUTHOR]

Jingmou Yu,1,2 Xin Xie,2 Liangliang Wang,3 Wenbo Liu,4 Huifeng Xu,4 Xiangmei Lu,4 Xiaofan Li,4 Jin Ren,2,4 Weidong Li2,5 1Huzhou Key Laboratory of Medical and Environmental Applications Technologies, School of Life Sciences, Huzhou University, Huzhou, 313000, People’s Republic of China; 2Jiangxi Provincial Key Laboratory of System Biomedicine, Jiujiang University, Jiujiang, 332000, People’s Republic of China; 3Affiliated Hospital of Jiujiang University, Jiujiang, 332000, People’s Republic of China; 4School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, 332000, People’s Republic of China; 5Jiujiang NO.1 People’s Hospital & Water of Life Hospital, Jiujiang, 332000, People’s Republic of ChinaCorrespondence: Jin Ren; Weidong Li, Email yanjiushengrj@126.com; 346880908@qq.comIntroduction: Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis.Methods: AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice.Results: D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity.Conclusion: The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.Graphical Abstract: Keywords: metastasis, dual-targeting, breast cancer therapy, reduction-sensitive micelles, drug delivery

Abstract Background Chemotherapy-related toxicity affects the quality of life (QOL) of patients with cancer. Measuring the QOL in breast cancer (BC) patients has been the focus of clinical practices and research in recent decades. This study aimed to assess the impact of BC medications on QOL of Sudanese patients with BC. Methods A cross-sectional study was conducted in Khartoum Oncology Hospital, Sudan, from November 2020 to March 2021. All patients diagnosed with BC were included in the study. QOL was assessed using the European Organization for Research and Treatment of Cancer quality of life (EORTC QLQ-C-30) and breast cancer supplementary module (QLQ-BR23). ANOVA, independent t-test and logistic regression analysis were used to assess the association between variables. Results Two hundred patients were enrolled in the study, with a mean age of 50 ± 11.7 years. 52.5% of the patients were on a conventional therapy whereas 40.5% and 7% received hormonal and HER2-targeted therapies, respectively. In QLQ-C30 scale, the global health-QOL status score was (53.2 ± 1.9), with 54.0% of patients having poor global health-QOL status. In the functional scale, the cognitive functioning was the highest score (80.7 ± 1.8). In QLQ-C30 symptom scale, the most distressing issue was financial difficulties (63.7 ± 2.9). In QLQ-BR23 scale, body image scored the worse functioning (47.7 ± 2.7), with 54.5% of patients having poor QOL. In QLQ-BR23 symptoms scale, “being upset by hair loss” was the highest disturbing symptom (62.1 ± 3.3), with 68.6% of patients having poor QOL. Global health status (P = 0.000), social (P = 0.000), emotional (P = 0.002) and role functioning (P = 0.000) were significantly higher in patients taking HER2-targeted or hormonal therapy compared to conventional therapy. The level of symptomatology was significantly low in patients taking HER2-targeted therapy or hormonal therapy (P = 0.000) than those on conventional therapy. Hormonal (OR = 3.7, p = 0.01) and HER2-targeted therapies (OR = 10.2, p = 0.04 ) were positive predictors of QOL. Conclusion BC survivors in Sudan had a low QOL/global health status. Hormonal and HER2-targeted therapies were predictors of good QOL.

Using a chemotherapeutic agent, such as doxorubicin (DOX), with a natural agent, such as silibinin (Sili), is highly valuable to minimize systemic toxicity. However, Sili and DOX face disadvantages, such as low aqueous solubility and poor bioavailability. Here, we have engineered a drug delivery cargo by decorating carboxylated graphene oxide (cGO) with an aptamer, HB5, for simultaneous delivery of DOX and Sili as a combination therapy against MCF-7 and SK-BR-3 breast cancer cells. The resulting Apt-cGO displayed a typical sheet-like nanostructure with a broad surface. The maximum entrapment efficiency was 70.42% and 84.22% for Sili and DOX, respectively. When the Apt-cGO-DOX-Sili nanocomposites were selectively taken up by breast cancer cells, the interaction between cGO and drugs was cleaved, causing releasing both Sili and DOX into the tumor cells, respectively. Compared to free drugs, Apt-cGO-DOX-Sili nanocomposites displayed higher cytotoxicity in vitro. Apt-cGO-DOX-Sili nanocomposites potentially suppressed some cancer cell survival signals. They accelerated cell apoptosis and increased Rb levels as well as reduced Akt, mTOR, NF-κB, and CDK2 levels. In conclusion, the developed Apt-cGO-DOX-Sili can be suggested as a simple and efficient drug delivery approach for breast chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2−. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends. [ABSTRACT FROM AUTHOR]

Simple Summary: The study's purpose was to determine whether neurotoxic signs in breast cancer patients receiving taxane (paclitaxel) chemotherapy correlate with retinal or corneal nerve changes in a longitudinal study combining oncological examinations with advanced biophotonic imaging techniques. Recruited breast cancer patients underwent regular monitoring sessions including the clinical assessment of their quality of life and neurological scores, ophthalmological status, retinal optical coherence tomography, and large area confocal laser scanning microscopy of their corneal subbasal nerve plexus (SNP). The study revealed two key breakthroughs: an observable increase in retinal thickness and the examination of identical corneal SNP large-area mosaics over time. Consequently, advanced biophotonic imaging techniques could represent a powerful diagnostic tool for the objective assessment of the severity of adverse events, wherein oncologists and ophthalmologists could benefit from each other, leading to a better outcome for the patient. A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients' scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers. [ABSTRACT FROM AUTHOR]

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 μg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis.

Breast cancer (BC) is the most prevalent malignant tumor, surpassing lung cancer as the most frequent malignancy in women. Drug resistance, metastasis, and immune escape are the major factors affecting patient survival and represent a huge challenge in BC treatment in clinic. The cell- and subcellular organelle-targeting nanoparticles-mediated targeted BC therapy may be an effective modality for immune evasion, metastasis, and drug resistance. Nanocarriers, efficiently delivering small molecules and macromolecules, are used to target subcellular apparatuses with excellent targeting, controlled delivery, and fewer side effects. This study summarizes and critically analyzes the latest organic nanoparticle-mediated subcellular targeted therapeutic based on chemotherapy, gene therapy, immunotherapy, and combination therapy in detail, and discusses the challenges and opportunities of nanoparticle therapy.

Low-level laser therapy (LLLT) has been used in cancer therapy by either activating chemicals, known as photodynamic treatment (PDT), or by heating the cancer cells through laser photon energy, known as photothermal therapy (PTT). In order to improve the effectiveness of LLLT, gold nanoparticles (AuNPs) are promising candidates that can serve as photo-absorbing agents. The current study evaluated the synergistic bioinhibitory effect of 532 nm green laser irradiation and AuNPs on MCF-7 cell line. The photo-absorption of AuNPs in visible and near-infrared regions can potentially improve low-level laser therapy. In this work, cells were treated with AuNPs (50 ± 0.15nm) at concentrations of 20 μg/ml and 50 μg/ml prior to irradiation with 0.002, 0.020, 0.060, and 0.100 W at different time frames (60–900 s). In the absence of AuNPs during laser therapy, cell inhibition was ranged at 25–40%. Interestingly, when cells were irradiated with the lowest dose of 2.40 J.cm−2 (0.002 W at 60 s) in the presence of AuNPs at the highest concentration of 50 μg/ml, a dramatic drop in cell density of more than 90% was observed (p < 0.05). Considering this discovery, AuNPs-assisted low-level laser therapy seems to be a promising alternative to therapy using high power laser. [ABSTRACT FROM AUTHOR]

There is literature supporting the view that chest radiation (CR) for the management of primary or metastatic cancer of the mediastinum and chest, including breast cancer is associated with all types of heart disease, including coronary artery disease (CAD), manifesting during long-term follow-up. This review explores the literature about the association of CR for the management of cancer and CAD, particularly focussing on breast cancer, and further on the differential between CR for right versus left breast cancer. The balk of the literature suggests that there is higher incidence of CAD in patients undergoing left versus right-CR for breast cancer, and that cardiologists and oncologists need to become involved systematically in their assessment prior to CR and at subsequent follow-up. [ABSTRACT FROM AUTHOR]

The limitations of self-assembled polymeric nanoparticles for cancer therapy, including instability in the bloodstream, non-specific targeting of cancer cells, and unregulated intracellular drug delivery, were effectively addressed by the development of core-shell SNX@PLL-FPBA/mHA NPs. The core was SNX@PLL-FPBA NPs prepared from polylysine conjugated 3-fluoro-4-carboxyphenylboronic acid (PLL-FPBA) self-assembly and SNX encapsulation, while the shell was methacrylate-modified hyaluronic acid (mHA) adhering to the core by electrostatic interactions and subsequently stabilized by photo-crosslinking, without the use of any organic solvent. SNX@PLL-FPBA/mHA NPs exhibited good stability in varying ionic strengths (0–0.30 M NaCl), pH levels (6.8 and 7.4), and plasma environments mimicking the blood, ensuring their efficacy in systemic circulation. The drug delivery from the nanoparticles was highly sensitive to ATP/Hyals stimuli (82 % within 48 h), closely mimicking the intracellular environment of breast cancer cells. The nanoparticles demonstrated good hemocompatibility and non-toxicity towards human skin fibroblasts. Efficient internalization of SNX@PLL-FPBA/mHA NPs by MCF-7 and MDA-MB-231 breast cancer cells was observed by CLSM and flow cytometry. The intracellular ATP/Hyals stimuli triggered the rapid drug delivery and induced cellular apoptosis. Thus, SNX@PLL-FPBA/mHA NPs were a promising drug nanocarrier for breast cancer therapy, offering improved stability, targeted delivery, and controlled drug release to enhance treatment outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-related toxicity affects the quality of life (QOL) of patients with cancer. Measuring the QOL in breast cancer (BC) patients has been the focus of clinical practices and research in recent decades. This study aimed to assess the impact of BC medications on QOL of Sudanese patients with BC.Methods: A cross-sectional study was conducted in Khartoum Oncology Hospital, Sudan, from November 2020 to March 2021. All patients diagnosed with BC were included in the study. QOL was assessed using the European Organization for Research and Treatment of Cancer quality of life (EORTC QLQ-C-30) and breast cancer supplementary module (QLQ-BR23). ANOVA, independent t-test and logistic regression analysis were used to assess the association between variables.Results: Two hundred patients were enrolled in the study, with a mean age of 50 ± 11.7 years. 52.5% of the patients were on a conventional therapy whereas 40.5% and 7% received hormonal and HER2-targeted therapies, respectively. In QLQ-C30 scale, the global health-QOL status score was (53.2 ± 1.9), with 54.0% of patients having poor global health-QOL status. In the functional scale, the cognitive functioning was the highest score (80.7 ± 1.8). In QLQ-C30 symptom scale, the most distressing issue was financial difficulties (63.7 ± 2.9). In QLQ-BR23 scale, body image scored the worse functioning (47.7 ± 2.7), with 54.5% of patients having poor QOL. In QLQ-BR23 symptoms scale, "being upset by hair loss" was the highest disturbing symptom (62.1 ± 3.3), with 68.6% of patients having poor QOL. Global health status (P = 0.000), social (P = 0.000), emotional (P = 0.002) and role functioning (P = 0.000) were significantly higher in patients taking HER2-targeted or hormonal therapy compared to conventional therapy. The level of symptomatology was significantly low in patients taking HER2-targeted therapy or hormonal therapy (P = 0.000) than those on conventional therapy. Hormonal (OR = 3.7, p = 0.01) and HER2-targeted therapies (OR = 10.2, p = 0.04 ) were positive predictors of QOL.Conclusion: BC survivors in Sudan had a low QOL/global health status. Hormonal and HER2-targeted therapies were predictors of good QOL. [ABSTRACT FROM AUTHOR]

Over the last decade, cancer mortality has decreased considerably, particularly in breast cancer thanks to better screening techniques and better therapeutic management. The significant increase in patient survival has led to the appearance of a certain number of events due to the side effects of the therapies used. Cardiovascular disease is the most frequently observed side effect in breast cancer, due to the direct toxicity of anti-cancer therapies but also due to traditional cardiovascular risk factors common to both of diseases. Anthracyclines, anti-HER2 therapies, chest radiotherapy and hormone therapy are the main causes of cardiotoxicity in breast cancer. It is important to know the rate of follow-up for cardiotoxicity screening and management. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) plays a crucial role in cancer diagnosis. The use of ultrasound contrast agents (UCAs) is inevitable in CEUS. However, current applications of UCAs primarily focus on enhancing imaging quality of ultrasound contrast rather than serving as integrated platforms for both diagnosis and treatment in clinical settings. In this study, a novel UCA, termed NPs-DPPA(C 3 F 8 ), is innovatively prepared using a combination of nanoprecipitation and ultrasound vibration methods. The DPPA lipid possesses inherent antiangiogenic and antitumor activities, and when combined with C 3 F 8 , it functions as a theranostic agent. Notably, the preparation of NPs-DPPA(C 3 F 8 ) is straightforward, requiring only one hour from raw materials to the final product due to the use of a single material, DPPA. NPs-DPPA(C 3 F 8 ) exhibits inherent antiangiogenic and biotherapeutic activities, effectively inhibiting triple-negative breast cancer (TNBC) angiogenesis and reducing VEGFA expression both in vitro and in vivo. Clinically, NPs-DPPA(C 3 F 8 ) enables simultaneous real-time imaging, tumor assessment, and antitumor activity. Additionally, through ultrasound cavitation, NPs-DPPA(C 3 F 8 ) can overcome the dense vascular walls to increase accumulation at the tumor site and facilitate internalization by tumor cells. The successful preparation of NPs-DPPA(C 3 F 8 ) offers a novel approach for integrating clinical diagnosis and treatment of TNBC., (© 2024 Wiley‐VCH GmbH.)

Xiao Mi,1 Meigeng Hu,1 Mingran Dong,1 Zhihong Yang,1 Xia Zhan,2 Xinyue Chang,1 Juan Lu,1 Xi Chen1 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100094, People’s Republic of China; 2Key Laboratory of Cleaner Production and Integrated Resource Utilization of China National Light Industry, Beijing Technology and Business University, Beijing, 100048, People’s Republic of ChinaCorrespondence: Xi Chen; Juan LuInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100094, People’s Republic of ChinaTel +86 10-57833257Email chenxi@implad.ac.cn; jlu@implad.ac.cnBackground: Baicalin (BAN) has attracted widespread attention due to its low-toxicity and efficient antitumor activity, but its poor water solubility and low bioavailability severely limit its clinical application. Development of a targeted drug delivery system is a good strategy to improve the antitumor activity of baicalin.Methods: We prepared a BAN nano-drug delivery system PEG-FA@ZIF-8@BAN with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta-potential, infrared (IR), ultraviolet (UV), x-ray diffraction (XRD), and Brunel-Emmett-Teller (BET), and examined the in vitro cytotoxicity and cellular uptake properties of PEG-FA@ZIF-8@BAN using MCF-7 cells. Lastly, we established a 4T1 tumor-bearing mouse model and evaluated its in vivo anti-mammary cancer activity.Results: The PEG-FA@ZIF-8@BAN nano-delivery system had good dispersion with a BAN loading efficiency of 41.45 ± 1.43%, hydrated particle size of 176 ± 8.1 nm, Zeta-potential of − 23.83 ± 1.1 mV, and slow and massive drug release in an acidic environment (pH 5.0), whereas release was 11.03% in a neutral environment (pH 7.4). In vitro studies showed that PEG-FA@ZIF-8@BAN could significantly enhance the killing effect of BAN on MCF-7 cells, and the folic acid-mediated targeting could lead to better uptake of nanoparticles by tumor cells and thus better killing of cancer cells. In vivo studies also showed that PEG-FA@ZIF-8@BAN significantly increased the inhibition of the proliferation of solid breast cancer tumors (p < 0.01 or p < 0.001).Conclusion: The PEG-FA@ZIF-8@BAN nano-drug delivery system significantly enhanced the anti-breast cancer effect of baicalin both in vivo and in vitro, providing a more promising drug delivery system for the clinical applications and tumor management.Keywords: metal-organic framework, folic acid response, baicalin, breast cancer therapy

Breast cancer becomes the most common type of cancer among women worldwide. Nowadays people seek noninvasive treatment for their illness. One of the methods in complementary and alternative medicine (CAM) is Ruqyah Syar'iyyah by reciting Quranic verses in the treatment. As the Holy Quran is the eternal miracle that challenged the world and affects all creatures in general, this study is aimed to disclose the effects of reciting Ruqyah Shar'iyyah as a treatment by evaluating the proliferation of breast cancer cell lines. The spiritual treatment was shown to improve the quality of life that gives better impacts on emotion and physical as well as increase immunity. This study applied the experimental method where MCF-7 cells were divided into two groups, the control, and the treatment group. During the treatment sessions, a compilation of several Qur'anic verses was recited by using the speakers. The study demonstrated that the cell proliferation percentage of the treatment group for both treatment periods (12 and 24 hours) decreased compared to the control group. This empirical study proved the miraculous effects of the Holy Quran on breast cancer cell lines. The study suggests the longer treatment times and repeated treatments would provide significant results for higher-grade cancer cells such as MCF-7 used in this study. [ABSTRACT FROM AUTHOR]

Rujing Chen,1,2,&ast; Shuting Ni,1,&ast; Wangyan Chen,1 Mei Liu,3 Jianfang Feng,4 Kaili Hu1 1Murad Research Center for Modernized Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaili HuMurad Research Center for Modernized Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaTel +86-21-5132-2534Fax +86-21-5132-2531Email kaili-hu@163.comJianfang FengSchool of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of ChinaEmail fengjianfang@vip.163.comPurpose: A novel RGD-modified PEGylated lipid-core micelle delivery system was designed to improve the anti-cancer effect of docetaxel on triple negative breast cancer (TNBC).Methods: The tumor-targeted lipid-core micelles loaded with docetaxel were prepared and characterized. Their morphology, particle size, zeta potential, entrapment efficiency, release profiles, and targeting effects were studied. The antitumor effects of the docetaxel-loaded nano-micelles were investigated in a MDA-MB-231 cell model in vitro and a MDA-MB-231 xenograft model in vivo.Results: The prepared RGD-modified docetaxel-loaded lipid-core micelles were spherical with a particle size of 16.44± 1.35 nm, zeta potential of − 19.24± 1.24 mV, and an encapsulation efficiency of 96.52± 0.43%. The drug delivery system showed sustained release properties and could significantly enhance docetaxel uptake by MDA-MB-231 tumor cells in vitro, which was proved to be a caveolae pathway mediated process requiring ATP, Golgi apparatus, and acid lysosomes. The results of the pharmacokinetic study displayed that the area under the curve of the targeted micelles was 3.2-times higher than that of docetaxel commercial injections. Furthermore, in a MDA-MB-231 tumor-bearing mice model, a higher antitumor efficacy than docetaxel commercial injections was displayed, and the safety experiments showed that the micellar material did not cause major organ damage after intravenous administration in mice.Conclusion: The novel RGD-modified PEGylated lipid-core micelle delivery system significantly improved the antitumor effects and reduced the side-effects of docetaxel, providing a promising therapeutics for the treatment of TNBC.Keywords: docetaxel, lipid-core micelles, RGD peptide, breast cancer therapy

Theranostic nanoparticles (NPs) have the potential to dramatically improve cancer management by providing personalized medicine. Inorganic NPs have attracted widespread interest from academic and industrial communities because of their unique physicochemical properties (including magnetic, thermal, and catalytic performance) and excellent functions with functional surface modifications or component dopants (e.g. , imaging and controlled release of drugs). To date, only a restricted number of inorganic NPs are deciphered into clinical practice. This review highlights the recent advances of inorganic NPs in breast cancer therapy. We believe that this review can provides various approaches for investigating and developing inorganic NPs as promising compounds in the future prospects of applications in breast cancer treatment and material science. [Display omitted] • The advantages of nanoparticles in chemotherapy have been expressed in breast cancer. • Inorganic NPs can target cancer biomarkers and used as contrast agent in cancer imaging • Boosting biological recognition and interaction competency of NPs are highlighted via surface modifications. [ABSTRACT FROM AUTHOR]

The therapeutic potential of quercetin‐loaded Pluronic® F‐127 (PF‐127)/Tween 80 mixed nanomicelles as a passive targeted drug delivery system for breast cancer therapy is evaluated. Quercetin‐loaded mixed nanomicelles with different mass ratios of drug/PF‐127/Tween 80 were prepared by thin‐film hydration method. The physical interactions of quercetin with PF‐127 and Tween 80 in an optimal ratio were investigated. The results of in vitro drug release experiments showed that the mixed micellar system exhibits a prolonged and sustained release behavior compared to the solution of free quercetin. The in vitro cytotoxicity studies of quercetin‐loaded mixed nanomicelles on breast cancer cells revealed that the encapsulated drug has a lower half‐maximal inhibitory concentration (IC50) value compared to the free drug. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer continues to be one of the leading causes of death in women, and the lack of treatment options for distant metastasis warrants the need to identify and develop more effective approaches. The aim of this study was to identify and validate targets that are associated with the survival and migration of the breast cancer cells in vitro through RNA interference (RNAi) approach. Methods: Linoleic‐acid‐modified polyethylenimine (PEI) polymer was used to screen a short interfering RNA (siRNA) library against numerous cell adhesion and cytoskeleton genes in MDA‐MB‐231 triple‐negative breast cell line, and the functional outcome of silencing was determined by growth and migration inhibition with further target validation studies. Results: Heat shock protein 90B1 (HSP90B1) was identified as a crucial gene that is known to be involved in various breast cancer machineries, including uncontrolled proliferation and brain metastasis. The success of this approach was also due to the use of hyaluronic acid (HA) additive in lipopolymer complexes that showed a profound impact in reducing the cell viability (~50%), migration (~40%), and mRNA transcript levels (~80%) with a physiologically relevant siRNA concentration of 60 nM. The use of Dicer‐substrate siRNA proved to be beneficial in target silencing, and a combinational treatment of integrin‐β1 (ITGB1) and HSP90B1 was effective in reducing the migration of the MDA‐MB‐231 and MDA‐MB‐436 breast cancer cells. Conclusion: This study demonstrates the potential to identify and silence targets using a lipid‐modified PEI/siRNA system and highlights the importance of HSP90B1 in the growth and migration of breast cancer cells. [ABSTRACT FROM AUTHOR]

This work aimed to fabricate a new photoluminescent bionanogel with both targeted anticancer drug delivery and bioimaging potentials. Briefly, at first photoluminescent carbon dots (CDs) were synthesized from the low-cost and more available black pepper with traditional medicinal properties. The as-synthesized dialdehyde carboxymethyl cellulose (DCMC) was used as a safe crosslinker for gelatin crosslinking in the presence of CDs (CDs/DCMC-Gel). Eventually, the residual amine functional groups of gelatin were used for the conjugation of CDs/DCMC-Gel with folic acid (FA) ((CDs/DCMC-Gel)-FA bionanogels). All employed physicochemical characterization methods approved the (CDs/DCMC-Gel)-FA bionanogels fabrication route. SEM analysis specified the spherical morphology with a diameter of ~70–90 nm for it. Curcumin (CUR) and doxorubicin (DOX) respectively were loaded with drug entrapment efficiency of about 44.0% and 41.4%. The release rate for both drugs in acidic conditions was higher than in physiological conditions. In vitro antitumor experiments; MTT, DAPI staining, cellular uptake, and cell cycle tests showed the superior anticancer effect of the CUR@DOX@(CDs/DCMC-Gel)-FA in comparison with free CUR@DOX. Moreover, the (CDs/DCMC-Gel)-FA acted as a hopeful bio-imaging tool. Taken together, the designed (CDs/DCMC-Gel)-FA could be proposed as a promising nanosystem for efficient chemotherapy. [Display omitted] • The photoluminescent CDs/DCMC-Gel was prepared via chemical crosslinking of CDs and gelatin mixture. • CDs/DCMC-Gel was conjugated with folic acid to obtain a targeted drug carrier. • CUR and DOX were co-loaded on (CDs/DCMC-Gel)-FA bionanogels. • Biocompatibility of (CDs/DCMC-Gel)-FA bionanogels was confirmed via in vitro cellular tests. [ABSTRACT FROM AUTHOR]

Abstract Breast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC.

Abstract The present paper reports on the local treatment of breast cancer from a historical perspective. A search for articles written in English was made in the Medline and EMBASE databases, and 40 papers were selected. Over the past 10 years, various randomized, controlled clinical trials on the local treatment of breast cancer indicated that patients with the samemolecular subtypemay receive different individualized surgical treatments aimed atoptimizing systemic adjuvant therapy. With a view to retaining the gainsmade in diseasefree and overall survival, surgical techniques have advanced from radical surgery to conservative mastectomies, thus reducing sequelae, while adjuvant and neoadjuvant therapies have contributed toward controlling the disease, both distant metastases and local recurrence. Current studies evaluate whether future breast cancer therapy may even succeed in eliminating surgery to the breast and axilla altogether.

The Notch signalling pathway is a highly conserved developmental signalling pathway, with vital roles in determining cell fate during embryonic development and tissue homeostasis. Aberrant Notch signalling has been implicated in many disease pathologies, including cancer. In this review, we will outline the mechanism and regulation of the Notch signalling pathway. We will also outline the role Notch signalling plays in normal mammary gland development and how Notch signalling is implicated in breast cancer tumorigenesis and progression. We will cover how Notch signalling controls several different hallmarks of cancer within epithelial cells with sections focussed on its roles in proliferation, apoptosis, invasion, and metastasis. We will provide evidence for Notch signalling in the breast cancer stem cell phenotype, which also has implications for therapy resistance and disease relapse in breast cancer patients. Finally, we will summarise the developments in therapeutic targeting of Notch signalling, and the pros and cons of this approach for the treatment of breast cancer.

Cancer therapies have undergone a tremendous progress over the past decade. Precision medicine provides a more tailored approach, making the combination of existing therapies more precise. Different types of cancers are characterized by unique biomarkers that are targeted using various genomic approaches by clinicians and companies worldwide to achieve efficient treatment with minimal side effects. Precision medicine has two broad approaches namely stratified and personalized medicine. The driver mutations could vary within a subtype while the same driver mutations could be found across different subtypes. Precision medicine has recently gained a lot of importance for breast cancer therapy. Various kinds of mutations like hotspot mutations, gene alterations, gene amplification mutations are targeted to design a more specific therapy. Apart from these known gene mutations there are various unknown mutations. Thus, tumor heterogeneity can pose a challenge to precision medicine. For breast cancer, one of the most successful models developed in case of precision medicine is the anti-HER2 therapies as HER2 was considered to have the worst prognosis being highly malignant. But now due to the advent of HER2 receptor targeted therapies, it has a good prognosis. Moreover, precision medicine helps in identifying if the drug molecules being used for the treatment of one kind of cancer can be beneficial in the treatment of another kind of cancer as well, considering the signaling pathways and machinery is similar in most of the cancers. This reduces the time for new drug development and is economically more feasible. Precision medicine will prove to be very advantageous in case of brain metastasis. [ABSTRACT FROM AUTHOR]

The stability of self-assembled drug nanocarriers during blood circulation and the controlled intracellular drug delivery are two challenges in cancer therapy. In this paper, we constructed an adenosine triphosphate (ATP)/hyaluronidase(Hyals) dually responsive core-shell hyaluronan/chitosan-based drug nanocarrier for breast cancer therapy, using SNX-loaded 3-fluoro-4-carboxyphenylboronic acid-conjugated quaternary ammonium chitosan nanoparticles (SNX@HTCC-FPBA NPs) as the core and crosslinked polyethylene glycol-/methacrylate-modified hyaluronic acid (mHA-PEG) as the shell. The formed SNX@HTCC-FPBA/mHA-PEG NPs were stable against salt ion strength, pH values and human plasma mimicking the bloodstream, but ATP/Hyals dually sensitive with a drug delivery of 85% within 48 h in the mimicking intracellular environment of breast cancer cells. These nanoparticles showed a low hemolysis of less than 3%, a high resistance to bovine serum albumin adsorption of 0.06 mg/mg, and an efficient internalization by two breast cancer cell lines (MCF-7 and MDA-MB-453). The cell culture indicated that they were friendly to human skin fibroblasts, but presented a close IC 50 value to SNX for MCF-7 (0.14 μg mL−1) and MDA-MB-453 (0.05 μg mL−1) at 48 h, respectively. Thus, SNX@HTCC-FPBA/mHA-PEG NPs were potential drug nanocarriers for breast tumor therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel PVA-PVP-MMT nanocarrier was fabricated for efficient Doxorubicin (Dox) delivery. • Controlled and pH-sensitive drug release was observed for PVA-PVP-Dox-MMT. • Cell viability assay indicated higher toxicity in breast cancer cells. • Flow cytometry showed the potential of the nanocarrier in inducing apoptosis. Breast cancer is a significant issue for women globally, and conventional cancer treatments have limitations in controlling the disease. Thus, it is crucial to design effective platforms for precise, tailored and targeted drug delivery. For such purpose, novel polyvinyl alcohol-polyvinylpyrrolidone-montmorillonite (PVA-PVP-MMT) nanocomposite with ratio of 1:2:1 (w/v%) has been designed herein for the delivery of doxorubicin (Dox) as a model drug to MCF-7 breast cancer cells. The nanocomposite has been characterized by different analytical techniques, including FT-IR, XRD, DLS, and FE-SEM. DLS and zeta potential measurements revealed an average hydrodynamic diameter of 402 nm and a nanocarrier surface charge of 42 mV, respectively. According to FE-SEM analysis, its size ranges from 200 nm to 340 nm and it shows semi-spherical and step-like morphologies. Drug release data revealed a pH-sensitive delivery (22 % and 37 % for pH 7.4 and 5.4 within 6 h, respectively) and in a controlled manner (about 50 % within 48 h). Biomedical tests, including MTT and apoptosis, were carried out to study the cancer cell suppression efficiency of PVA-PVP-Dox-MMT. The MTT assay indicated 42 % cytotoxicity after 24 h of treatment with the nanocarrier, and the flow cytometry demonstrated 40 % apoptosis. The results of this study support that the developed PVA-PVP-Dox-MMT nanocarrier is an effective drug delivery platform and a very promising candidate for cancer treatment. [ABSTRACT FROM AUTHOR]

Gene therapy is considered to be a valuable strategy for effective cancer treatment. However, the development of effective delivery systems that can specifically deliver gene materials, such as siRNA to tumor tissues plays a critical role in cancer therapy. In the present study, we have developed a novel complex that is based on an electrostatic interaction between cationic polyurethane ionene (CPUI) nanoparticles and an anti-signal transducer and activator of transcription 3 (STAT3) siRNA. For active targeting, hyaluronic acid (HA) was used to coat the complexes, which significantly reduced the cytotoxicity of the blank nanocarriers while demonstrating high transport efficiency of the siRNA via the CD44-mediated endocytosis pathway in MCF-7 breast cancer cells. The targeted nanocarriers (HA/CPUI/siRNA) showed significantly higher cellular internalization in flow cytometry and confocal microscopy compared with the non-targeted system (CPUI/siRNA). In addition, the incorporation of HA on the surface of the complexes resulted in significantly greater suppression of the STAT3 gene compared to the corresponding non-targeted formulation. Whole-body fluorescence images showed more significant tumor accumulation of the targeted nanocarriers in 4T1 breast tumor-bearing mice. Therefore, HA/CPUI/siRNA nanocarriers are an interesting option for the siRNA-targeted treatment of breast cancer cells. [Display omitted] • Novel gene delivery system based on cationic polyurethane ionene (CPUI) nanoparticles, for breast cancer treatment. • A complex utilizing electrostatic interaction between CPUI nanoparticles and siRNA. • For active targeting, hyaluronic acid (HA) was used for coating of the complexes. • Cellular uptake, cytotoxicity, and suppression of the STAT3 gene were enhanced for the targeted nanocarriers. • Whole-body fluorescence images showed more significant tumor accumulation of the targeted nanocarriers in vivo. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer, the most common invasive cancer of women, is a malignant neoplasm and the second main cause of cancer death. Resistance to paclitaxel (Taxol), one of the frequently used chemotherapy agents for breast cancer, presents a major clinical challenge. Recent studies revealed that metabolic alterations of cancer cells play important roles in chemo-resistance. Materials and methods In this study, Human breast cancer cells, BT474, SKBR3 and MCF7 were used to study the causal relationship between the lactate exporter, MCT1 (SLC16A1)-modulated glucose metabolism and Taxol resistance of breast cancer cells. Taxol resistant breast cancer cells were established. The intracellular lactate and extracellular lactate levels as well glucose uptake and oxygen consumption were measured. MicroRNA-124 expressions were detected by qRT-PCR from both breast cancer patient samples and breast cancer cells. Target of miR-124 was predicted and verified by Western blot and luciferase assay. An xenograft mice model was established and evaluated for the in vivo tumor therapeutic effects of MCT1 inhibitor plus microRNA-124 treatments. Results Low toxic Taxol treatments promoted cellular glucose metabolism and intracellular lactate accumulation with upregulated lactate dehydrogenase-A (LDHA) and MCT1 expressions. By establishing Taxol resistant breast cancer cell line, we found Taxol resistant cells exhibit upregulated LDHA and MCT1 expressions. Furthermore, glucose consumption, lactate production and intracellular ATP were elevated in Taxol resistant MCF7 cells compared with their parental cells. The miR-124, a tumor suppressive miRNA, was significantly downregulated in Taxol resistant cells. Luciferase assay and q-RT-PCR showed MCT1 is a direct target of miR-124 in both breast cancer cell lines and patient specimens. Moreover, co-treatment of breast cancer cells with either MCT1 inhibitor or miR-124 plus Taxol led to synergistically cytotoxic effects. Importantly, based on in vitro and in vivo results, inhibition of MCT1 significantly sensitized Taxol resistant cells. Finally, rescue experiments showed restoration of MCT1 in miR-124 overexpressing cells promoted Taxol resistance. Conclusions This study reveals a possible role of miRNA-214-mediated Taxol resistance, contributing to identify novel therapeutic targets against chemoresistant breast cancers.

Neonatal Nav1.5 (nNav1.5) is the alternative splice variant of Nav1.5 and it has been widely associated with the progression of breast cancer. The immunological context of nNav1.5 with respect to breast cancer metastases remains unexplored. The presence of antibodies against nNav1.5 may highlight the immunogenicity of nNav1.5. Hence, the aim of the present study was to detect the presence of antineonatal Nav1.5 antibodies (antinNav1.5-Ab) in the serum of patients with breast cancer and to elucidate the effects of breast cancer therapy on its expression. A total of 32 healthy female volunteers and 64 patients with breast cancer were randomly recruited into the present study as the control and breast cancer group, respectively. Patients with breast cancer were divided equally based on their pre- and ongoing-treatment status. Serum samples were tested with in-house indirect enzyme-linked immunosorbent assay (ELISA) to detect antinNav1.5-Ab, CD25 (T regulatory cell marker) using an ELISA kit and Luminex assay to detect the expression of metastasis-associated cytokines, such as vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-10, IL-8, chemokine (C-C motif) ligand 2 and tumor necrosis factor-alpha (TNF-α) The mean difference in the expression of antinNav1.5-Ab among the three groups (control, pretreatment and ongoing-treatment) was significant (P=0.0005) and the pretreatment breast cancer group exhibited the highest expression. The concentration of CD25 was highest in the pretreatment breast cancer group compared with the control and ongoing-treatment groups. There was a signifi- cant positive correlation between antinNav1.5-Ab and IL-6 in the pretreatment group (r=0.7260; P=0.0210) and a significant negative correlation between antinNav1.5-Ab and VEGF in the ongoing-treatment group (r=-0.842; P-value=0.0040). The high expression of antinNav1.5-Ab in the pretreatment group was in accordance with the uninterrupted presence of metastasis and highlighted the immunogenicity of nNav1.5 whereas the low expression of antinNav1.5-Ab in the ongoing-treatment group reflected the efficacy of breast cancer therapy in eliminating metastases. The augmented manifestation of T regulatory cells in the pretreatment group highlighted the functional role of nNav1.5 in promoting metastasis. The parallel expression of antinNav1.5-Ab with the imbalanced expression of cytokines promoting metastasis (IL-8, IL-6 and TNF-α) and cytokines that prevent metastasis (IL-10) indicated the role of nNav1.5 in breast cancer growth. The expression of antinNav1.5-Ab in accordance to the metastatic microenvironment indicates the immunogenicity of the protein and highlights the influence of breast cancer therapy on its expression level. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu® without drainage is equal/ non-inferior to standard mastecomy with drainage. Methods: The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups. Results: Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu® group than in the drainage group, especially aspirations of clinically relevant seromas (p = 0.014). The TissuGlu® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu® compared to standard drainage couldn't be reached. Discussion: The present evaluation shows no advantage of the tissue adhesive TissuGlu® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life. [ABSTRACT FROM AUTHOR]

Abstract Background Self-administered health-status questionnaires are important tools in epidemiology. The objective of the presented validation study is to measure the agreement between breast cancer patients’ self-reports and their physicians’ information on late cardiac events, and to investigate determinants of agreement. To estimate possible misclassification is an important requirement for observational studies on cardiovascular endpoints. Methods A retrospective, multi-center cohort study included 11,982 women diagnosed with breast cancer in Germany in 1998–2008. In 2014, a questionnaire survey assessed cardiovascular risk factors and incident cardiac events after therapy. A validation study was conducted, based on a sample of 3091 breast cancer patients from two university hospitals. Among them, 2261 women (73%) sent back the questionnaire on cardiovascular events, and 1316 women gave consent to request medical records from their general practitioners. A total of 1212/1316 (92.1%) medical records could be obtained for validation. Cohen’s kappa coefficient was calculated, and multivariate regression was applied to study the influence of patient characteristics on agreement between both data sources. Results Overall agreement for the composite endpoint of any cardiac event was 84.5% (kappa 0.35). Of 1055 breast cancer patients reporting no cardiac event, 950 (90%) had no such diagnosis in physicians’ medical records. A total of 157 breast cancer survivors indicated a cardiac event, and the same diagnosis was confirmed by GPs for 74 (47%) women. For specific diagnoses, moderate to substantial agreement of self-reports was found for myocardial infarction (kappa 0.54) and stroke (kappa 0.61). Poor to fair agreement was present for angina pectoris, valvular heart disease, arrhythmia, and congestive heart failure. Younger age, higher education and a more recent cancer diagnosis were found to be associated with greater total agreement. Conclusions For the composite endpoint, survivors of breast cancer report the absence of cardiac disease accurately. However, for specific diagnoses, self-reported morbidity data from breast cancer patients may not fully agree with information from physicians. The agreement is moderate for acute events like myocardial infarction and stroke, but poor to fair for chronic diseases.

Objective: A previous randomized phase II study showed that neoadjuvant nab-paclitaxel (nab-PTX) 100 mg/m2) was effective and well-tolerated in patients with HER2-negative early-stage breast cancer, compared with docetaxel (DTX). We evaluated patient outcomes in terms of the Functional Assessment of Cancer Therapy-Breast (FACT-B), as a measure of health-related quality of life (HRQoL).Materials and Methods: Stage I–III HER2-negative breast cancer patients from the previous study were included. They received either four cycles of nab-PTX (100 mg/m2 days 1/8/15) every 4 weeks, or DTX (75 mg/m2 day 1) every 3 weeks, both followed by four cycles of 5-fluorouracil/ epirubicin/cyclophosphamide (FEC). Patients completed a health-related quality-of-life questionnaire at baseline, after one and four cycles of taxanes, before administration of FEC, and after administration of one and four cycles of FEC.Results: Thirty-six eligible patients were enrolled. The baseline characteristics of the two groups were well balanced. FACT-B scores at baseline and after four cycles of taxanes were 115/108 (DTX/nab-PTX) and 99/92, respectively. There were no significant differences between DTX and nab-PTX for FACT-B, FACT-B-Trial Outcome Index (FACT-B-TOI) and FACT-General. FACT-B and FACT-B TOI scores tended to decrease after one cycle and after four cycles of chemotherapy which did not recover to the baseline scores through the end of chemotherapy in each group.Conclusion: There were no significant safety differences between nab-PTX and DTX. HRQoL tended to decrease during taxane-based anticancer treatment, with no significant differences between the treatments. We suggest that the HRQoL questionnaire has limited ability to evaluate different chemotherapy schedules. Trial registration UMIN000009855. Nov 20, 2012 registered.

Trevor S Mafu,1 Alison V September,1 Delva Shamley2 1Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, 2Clinical Research Centre, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Abstract: Shoulder morbidity is a well-documented sequela of breast cancer treatment, which includes various manifestations such as pain, reduced range of motion, and lymphedema, among others. The multifactorial nature of such morbidities has long been appreciated, and research on reliable risk predictors of development thereof still continues. Previous studies have demonstrated the potential of different types of physical therapy to treat such shoulder problems, and the integration of such interventions into routine care for breast cancer survivors is a requirement in most high-income countries. Although patients at risk for developing shoulder problems would most likely benefit from posttreatment physical therapy, currently, there is no gold standard for identifying this patient group. This is particularly important in low- and middle-income countries where scarce monetary resources need to be directed specifically to those most in need. Modulators of the angiogenesis pathway have been implicated in noncancer shoulder conditions such as rotator cuff disease, adhesive capsulitis, and tendon injuries. The present review summarizes the role of angiogenesis in the development of shoulder morbidity among breast cancer survivors and sets forth the rationale for our belief that angiogenesis signaling may help explain a proportion of the reported clinical variability noted in the development of shoulder pain and dysfunction and upper-limb lymphedema after breast cancer treatment. Keywords: angiogenesis, shoulder dysfunction, cytokines, polymorphism, breast cancer therapy

Breast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC. [ABSTRACT FROM AUTHOR]

As a synthetic clay material, laponite RDS (LR) was investigated as an effective drug carrier as a result of the special nanodisk structure together with the negative-charged surface to achieve enhanced cellular uptake and targeted delivery. In this research work, the synthesized oligomeric hyaluronic acid-aminophenylboronic acid (oHA-APBA) was entangled onto LR nanodisks to fabricate a valid targeted platform for breast cancer therapy. Briefly, through the formation of amide bonds, 3-APBA was connected to the chain of oHA with a substituted ratio of 4.0 ± 0.2% to synthesize oHA-APBA copolymer. Thereafter, doxorubicin (DOX) was inserted into the interlayer space of LR by the way of the ion exchange process, followed by an assembly with oHA-APBA as a targeted protection layer. The satisfactory drug encapsulation efficiency (> 80%) and narrow size distribution were achieved. The in vitro drug release study demonstrated the release of DOX from DOX@LR/oHA-APBA was sustained and acid dependent. In addition, after fitting the drug cumulative release of DOX@LR/oHA-APBA under different pH conditions with several kinetic models, it was identified that drug release from DOX@LR/oHA-APBA nanohybrids at pH 5.0 was mainly dependent on both diffusion and ion exchange effects. However, under the condition of pH 7.4, the drug was most efficiently released by diffusion effect. Importantly, DOX@LR/oHA-APBA showed remarkable cellular uptake and intracellular drug distribution in MCF-7 cells, which were consistent with inhibitory ability against MCF-7 cells. Hence, the high DOX loading capacity and enhanced cellular tracking can enlighten LR/oHA-APBA as an effective drug delivery carrier for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Among all cancer types, breast cancer (BC) still stands as one of the most serious diseases responsible for a large number of cancer-associated deaths among women worldwide, and diagnosed cases are increasing year by year worldwide. For a very long time, hormonal therapy, surgery, chemotherapy, and radiotherapy were used for breast cancer treatment. However, these treatment approaches are becoming progressively futile because of multidrug resistance and serious side effects. Consequently, there is a pressing demand to develop more efficient and safer agents that can fight breast cancer belligerence and inhibit cancer cell proliferation, invasion and metastasis. Currently, there is an avalanche of newly designed and synthesized molecular entities targeting multiple types of breast cancer. This review highlights several important synthesized compounds with promising anti-BC activity that are categorized according to their chemical structures.