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Nanoparticles are excellent platforms for several biomedical applications, including cancer treatment. They can incorporate different molecules to produce combinations of chemotherapeutic agents, radionuclides, and targeting molecules to improve the therapeutic strategies against cancer. These specific nanosystems are designed to have minimal side effects on healthy cells and better treatment efficacy against cancer cells when compared to chemotherapeutics, external irradiation, or targeted radiotherapy alone. In colorectal cancer, some metal and polymeric nanoparticle platforms have been used to potentialize external radiation therapy and targeted drug delivery. Polymeric nanoparticles, liposomes, albumin-based nanoparticles, etc., conjugated with PEG and/or HLA, can be excellent platforms to increase blood circulation time and decrease side effects, in addition to the combination of chemo/radiotherapy, which increases therapeutic efficacy. Additionally, radiolabeled nanoparticles have been conjugated to target specific tissues and are mainly used as agents for diagnosis, drug/gene delivery systems, or plasmonic photothermal therapy enhancers. This review aims to analyze how nanosystems are shaping combinatorial therapy and evaluate their status in the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Surface functionalization of metallic nanoparticles (NPs) with external groups can be engineered to fabricate sensors that are responsive to various stimuli like temperature, pH, and numerous ions. Herein, we report the synthesis of gold nanoparticles (GNPs) functionalized with 3-mercaptopropionic acid (GNPs-MPA) and the doping of these nanoparticles into hydrogel materials using the breathing-in/breathing-out (BI-BO) method. MPA has a carboxyl group that becomes protonated and, thus, ionized at a pH below its pKa (4.32); hence, the GNPs-MPA solutions and gels were mostly pH-responsive in the range of 3–5. Optical properties were assessed through ultraviolet-visible (UV-Vis) spectroscopy, namely: transmission and absorption, and the parameters used to quantify the pH changes were the full width at half maximum (FWHM) and position of surface plasmon resonance (SPR). The solutions and gels gradually changed their colors from red to indigo with pH decrementation from 5 to 3, respectively. Furthermore, the solutions' and doped gels' highest FWHM sensitivities towards pH variations were 20 nm and 55 nm, respectively, while the SPR's position sensitivities were 18 nm and 10 nm, respectively. Also, transmission and scanning electron microscopy showed synchronized dispersion and aggregation of NPs with pH change in both solution and gel forms. The gel exhibited excellent repeatability and reversibility properties, and its response time was instantaneous, which makes its deployment as a colorimetric pH-triggered sensor practical. To the best of our knowledge, this is the first study that has incorporated GNPs into hydrogels utilizing the BI-BO method and demonstrated the pH-dependent optical and colorimetric properties of the developed nanocomposites. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of death all over the globe among women. Nanotechnology has emerged recently to overcome the limitations of the traditional drug delivery system. Conventional chemotherapies have several side effects that damage the immune system and other organs. Several other cancer treatments cause the proliferation of normal cells, making them cancerous due to nonspecific targeting, inability to enter the core of the tumor, and poor solubility. To overcome the problems of chemotherapies, nanotechnology has come up with the direct killing of a tumor cell with fewer side effects. Nanoparticles are designed to recognize the cancer cells and provide accurate drug delivery without interacting with the healthy cells. The use of nanoparticles with anticancer drug therapies has shown promising effects in the killing of cancer cells. The major objective of this review is to discuss the role of Heat Shock Protein 90 (Hsp90) in breast cancer and its treatment by targeted therapy via nanotechnology. This review covers research published since 2001 describing the nanotechnology mediated Hsp90 targeted breast cancer therapy. [ABSTRACT FROM AUTHOR]

Cancer is still one of the most common causes of death today despite advances in its detection and treatment. The present article reviews the application of marine-based gold nanoparticles in the diagnosis and treatment of cancer. The main data were collected from original research articles on the application of different marine-based gold nanoparticles in detecting and imaging cancer cells as well as in drug delivery systems and treatment of cancer. The results show the excellent anticancer potential of both gold nanoparticles and natural marine products. The most studied marine-based gold nanomaterial was chitosan-based ones, in which the role of chitosan is a stabilizer not an anticancer agent. Despite the excellent anticancer potential of different marine natural products, limited studies have been conducted using gold nanoparticles in their composition in cancer therapy. Moreover, most of these studies are related to their application as a drug delivery system not an anticancer drug. Although there are serious challenges in the application of nanoparticles in medicine, marine-based gold nanomaterials may promise an interesting novel strategy in the oncology field. [ABSTRACT FROM AUTHOR]

Modern biomedicine aims to develop integrated solutions that use medical, biotechnological, materials science, and engineering concepts to create functional alternatives for the specific, selective, and accurate management of medical conditions. In the particular case of tissue engineering, designing a model that simulates all tissue qualities and fulfills all tissue requirements is a continuous challenge in the field of bone regeneration. The therapeutic protocols used for bone healing applications are limited by the hierarchical nature and extensive vascularization of osseous tissue, especially in large bone lesions. In this regard, nanotechnology paves the way for a new era in bone treatment, repair and regeneration, by enabling the fabrication of complex nanostructures that are similar to those found in the natural bone and which exhibit multifunctional bioactivity. This review aims to lay out the tremendous outcomes of using inorganic nanoparticles in bone healing applications, including bone repair and regeneration, and modern therapeutic strategies for bone-related pathologies. [ABSTRACT FROM AUTHOR]

Nanofibers (NFs) with practical drug-loading capacities, high stability, and controllable release have caught the attention of investigators due to their potential applications in on-demand drug delivery devices. Developing novel and efficient multidisciplinary management of locoregional cancer treatment through the design of smart NF-based systems integrated with combined chemotherapy and hyperthermia could provide stronger therapeutic advantages. On the other hand, implanting directly at the tumor area is a remarkable benefit of hyperthermia NF-based drug delivery approaches. Hence, implantable smart hyperthermia NFs might be very hopeful for tumor treatment in the future and provide new avenues for developing highly efficient localized drug delivery systems. Indeed, features of the smart NFs lead to the construction of a reversibly flexible nanostructure that enables hyperthermia and facile switchable release of antitumor agents to eradicate cancer cells. Accordingly, this study covers recent updates on applications of implantable smart hyperthermia NFs regarding their current scope and future outlook. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants., (© 2023 Wiley Periodicals LLC.)

Presently, nanocarriers (NCs) have gained huge attention for their structural ability, good biocompatibility, and biodegradability. The development of effective NCs with stimuli-responsive properties has acquired a huge interest among scientists. When developing drug delivery NCs, the fundamental goal is to tackle the delivery-related problems associated with standard chemotherapy and to carry medicines to the intended sites of action while avoiding undesirable side effects. These nanocarriers were able of delivering drugs to tumors through regulating their pH, temperature, enzyme responsiveness. With the use of nanocarriers, chemotherapeutic drugs could be supplied to tumors more accurately that can equally encapsulate and deliver them. Material carriers for chemotherapeutic medicines are discussed in this review keeping in viewpoint of the structural properties and targeting methods that make these carriers more therapeutically effective, in addition to metabolic pathways triggered by drug-loaded NCs. Largely, the development of NCs countering to endogenous and exogenous stimuli in tumor regions and understanding of mechanisms would encourage the progress for tumor therapy and precision diagnosis in future. [ABSTRACT FROM AUTHOR]

Fitness of cells is dependent on protein homeostasis which is maintained by cooperative activities of protein chaperones and proteolytic machinery. Upon encountering protein-damaging conditions, cells activate the heat-shock response (HSR) which involves HSF1-mediated transcriptional upregulation of a group of chaperones – the heat shock proteins (HSPs). Cancer cells experience high levels of proteotoxic stress due to the production of mutated proteins, aneuploidy-induced excess of components of multiprotein complexes, increased translation rates, and dysregulated metabolism. To cope with this chronic state of proteotoxic stress, cancers almost invariably upregulate major components of HSR, including HSF1 and individual HSPs. Some oncogenic programs show dependence or coupling with a particular HSR factor (such as frequent coamplification of HSF1 and MYC genes). Elevated levels of HSPs and HSF1 are typically associated with drug resistance and poor clinical outcomes in various malignancies. The non-oncogene dependence ("addiction") on protein quality controls represents a pancancer target in treating human malignancies, offering a potential to enhance efficacy of standard and targeted chemotherapy and immune checkpoint inhibitors. In cancers with specific dependencies, HSR components can serve as alternative targets to poorly druggable oncogenic drivers. [ABSTRACT FROM AUTHOR]

This study reports on the green and cost-efficient synthesis of gold nanoparticles from three different red algae extracts. The nanoparticles synthesized were fully characterized by UV-Vis spectroscopy, HRTEM, and Z-potential. Relevant components occurring in the extracts, such as polysaccharides or phenolic content, were assessed by analytical techniques such as spectrophotometric assays and liquid chromatography. Finally, the antioxidant, antitumoral, and anti-inflammatory potential of both the extracts and the gold nanoparticles synthesized were analyzed in order to determine a possible synergistic effect on the nanoparticles. The results obtained confirmed the obtainment of gold nanoparticles with significant potential as immunotherapeutic agents. The therapeutic potential of these nanoparticles could be higher than that of inert gold nanoparticles loaded with bioactive molecules since the former would allow for higher accumulation into the targeted tissue. [ABSTRACT FROM AUTHOR]

Autologous bone grafts are commonly used as the gold standard to repair and regenerate diseased bones. However, they are strongly associated with postoperative complications, especially at the donor site, and increased surgical costs. In an effort to overcome these limitations, tissue engineering (TE) has been proposed as an alternative to promote bone repair. The successful outcome of tissue engineering depends on the microstructure and composition of the materials used as scaffold. Decellularized bone matrix-based biomaterials have been applied as bioscaffolds in bone tissue engineering. These biomaterials play an important role in providing the mechanical and physical microenvironment needed by cells to proliferate and survive. Decellularized extracellular matrix (dECM) can be used as a powder, hydrogel and electrospun scaffolds. These bioscaffolds mimic the native microenvironment due to their structure similar to the original tissue. The aim of this review is to highlight the bone decellularization techniques. Herein we discuss: (1) bone structure; (2) properties of an ideal scaffold; (3) the potential of decellularized bone as bioscaffolds; (4) terminal sterilization of decellularized bone; (5) cell removing confirmation in decellularized tissues; and (6) post decellularization procedures. Finally, the improvement of bone formation by dECM and the immunogenicity aspect of using the decellularized bone matrix are presented, to illustrate how novel dECM-based materials can be used as bioscaffold in tissue engineering. A comprehensive understanding of tissue engineering may allow for better incorporation of therapeutic approaches in bone defects allowing for bone repair and regeneration. [ABSTRACT FROM AUTHOR]

In this study, four different nanofibers consisting of gelatin (Gel), doxorubicin (DOX) with gel (DOX@Gel), a composite of gel with poly(ethylene glycol) (PEGylated-gel), and DOX@PEGylated-gel were fabricated. Subsequently, the nanofibers were thermally cross-linked in order to offer a stable and biocompatible alternative for the biological applications of nanofibers such as drug delivery and tissue engineering. Nanofibers were characterized by scanning electron microscopy, Fourier Transform-Infrared Spectroscopy (FT-IR), and confocal microscopy. The formation of smooth, continuous, and uniform nanofibers was observed and the addition of PEG resulted in an increase whereas the incorporation of DOX into nanofibers had no significant change in the diameter of nanofibers. Crosslinking also enlarged the diameter of all nanofibers and the most dramatic increase was observed 53% by DOX@PEGylated-gel. Afterward, the biological performance of the nanofibers was investigated by drug release profile, cytotoxicity on A549 cell line as well as antimicrobial activity with E. coli and S. aureus. The results indicate an enhanced drug release profile, moderate antimicrobial activity, and reasonable cytotoxic efficiency for thermally cross-linked nanofibers compared to uncross-linked nanofibers. [ABSTRACT FROM AUTHOR]

Metal nanoparticles are widely applied in various biomedical applications because of their unique physicochemical properties. The new and unique properties of gold nanoparticles (AuNPs) including, biocompatibility, low cytotoxicity, and optical properties, make them valuable for applications of biomedical fields including, biosensing, bioimaging, cancer therapy of cancer, and drug delivery. Utilization of AuNPs in radiotherapy and photothermal therapy has created a novel platform for primary diagnosis and cancer therapy. Owing to AuNPs' large surface area, chemical functional groups or biological molecules like drug molecules can be immobilized on gold surface. Thus, the surface functionalization of AuNPs makes them a good carrier for targeted drug delivery. This review focuses on new progress in processes of the functionalization of AuNPs and their possible biomedical applications. [ABSTRACT FROM AUTHOR]

Geldanamycin (GDM) has been modified by different type neutral/acidic/basic substituents (1–7) and by quinuclidine motif (8), transformed into ammonium salts (9–13) at C(17). These compounds have been characterised by spectroscopic and x-ray methods. Derivative 8 shows better potency than GDM in MCF-7, MDA-MB-231, A549 and HeLa (IC50s = 0.09–1.06 µM). Transformation of 8 into salts 9–13 reduces toxicity (by 11-fold) at attractive potency, e.g. MCF-7 cell line (IC50∼2 µM). Our studies show that higher water solubility contributes to lower toxicity of salts than GDM in healthy CCD39Lu and HDF cells. The use of 13 mixtures with potentiators PEI and DOX enhanced anticancer effects from IC50∼2 µM to IC50∼0.5 µM in SKBR-3, SKOV-3, and PC-3 cancer cells, relative to 13. Docking studies showed that complexes between quinuclidine-bearing 8–13 and Hsp90 are stabilised by extra hydrophobic interactions between the C(17)-arms and K58 or Y61 of Hsp90. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors (HDACi) are cancer therapeutics that operate at the epigenetic level and which have recently gained wide attention. However, the applications of HDACi are generally hindered by their poor physicochemical characteristics and unfavorable pharmacokinetic profile. Inspired by the approved nanomedicine-based drugs in the market, nanocarriers could provide a resort to circumvent the limitations imposed by HDACi. Enhanced tumor targeting, improved cellular uptake and reduced toxicity are major advantages offered by HDACi-loaded nanoparticles. More importantly, site-specific drug delivery can be achieved via engineered stimuli-responsive nanosystems. In this review we elucidate the anticancer mechanisms of HDACi and their structure–activity relationships, with a special focus on their nanomedicine-based delivery, different drug loading concepts and their implications. [ABSTRACT FROM AUTHOR]

A Kinase Interacting Protein 1 (AKIP1) is found to be overexpressed in a variety of human cancers and associated with patients' worse prognosis. Several studies have established AKIP1's malignant functions in tumor metastasis, angiogenesis, and chemoradiotherapy resistance. However, the mechanism of AKIP1 involved in accelerating glioblastoma (GBM) progression remains unknown. Here, we showed that the expression of AKIP1 was positively correlated with the glioma pathological grades. Down-regulating AKIP1 greatly impaired the proliferation, colony formation, and tumorigenicity of GBM cells. In terms of the mechanism, AKIP1 cooperates with transcriptional factor Yin Yang 1 (YY1)-mediated Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) transcriptional activation, enhancing the stability of Epidermal Growth Factor Receptor (EGFR). YY1 was identified as a potential transcriptional factor of HSP90AA1 and directly interacts with AKIP1. The overexpression of HSP90α significantly reversed AKIP1 depletion incurred EGFR instability and the blocked cell proliferation. Moreover, we further investigated the interacted pattern between EGFR and HSP90α. These findings established that AKIP1 acted as a critical oncogenic factor in GBM and uncovered a novel regulatory mechanism in EGFR aberrant expression., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The use of engineered nanoparticles in the environment and human life has increased in the last 20 years. The risk assessment concerning application of nanomaterials in biological systems requires their thorough characterization. Understanding the correlations between physicochemical properties of nanoparticles concerning not only the size, particle size distribution, number concentration, degree of aggregation, or agglomeration but also solubility, stability, binding affinity, surface activity, chemical composition, and nanoparticle synthesis yield allows their reliable characterization. Thus, to find the structure-function/property relationship of nanoparticles, multifaceted characterization approach based on more than one analytical technique is required. On the other hand, the increasing demand for identification and characterization of nanomaterials has contributed to the continuous development of spectrometric techniques which enables for their qualitative and quantitative analysis in complex matrices giving reproducible and reliable results. This review is aimed at providing a discussion concerning four main aspects of nanoparticle characterization: nanoparticle synthesis yield, particle size and number concentration, elemental and isotopic composition of nanoparticles, and their surface properties. The conventional and non-conventional spectrometric techniques such as spectrophotometry UV-Vis, mass spectrometric techniques working in conventional and single-particle mode, or those based on optical emission detection systems are described with special emphasis paid on their advantages and drawbacks. The application and recent advances of these methods are also comprehensively reviewed and critically discussed., (© 2023. The Author(s).)

A series of biodegradable poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) (PCEC) triblock copolymers had been successfully synthesized by ring-opening polymerization of ε-caprolactone initiated by PEG, which were characterized by proton nuclear magnetic resonance analysis (1H NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The gel–sol phase transition diagram of synthesized copolymers was recorded using test tube inverting method. PCECs could form injectable solutions via self-assembly and automatically turned into non-flowing gels at physiological temperatures. Their aqueous solution displayed special gel–sol transition behavior with temperature increasing from 0 to 60°C, when the polymer concentration was above corresponding critical gel concentration (CGC). In vitro release experiments at pH 7.4 showed that after 24 h at least approximately 75–80% of doxorubicin (DOX) can be protected from enzyme or hydrolytic degradation. Therefore, thermosensitive PCECs have many advantages, such as simple drug formulation, no organic solvent, a sustained drug release behavior. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles are smart materials that have been commonly used in medicine for diagnostic imaging, drug delivery, and therapeutic applications. In this study, Iron oxide nanoparticles and Doxorubicin (DOX)- Chrysin (Chr), were absorbed into triblock copolymer (PCL-PEG-PCL) for narrow behavior. PCL-PEG triblock copolymers were synthesized by ring-opening polymerization of ε-caprolactone (ε-CL) with polyethylene glycol (EG) as an initiator. The bulk properties and chemical structure of these copolymers were characterized using Fourier transform infrared spectroscopy and ¹H-NMR. In adding together, the consequential particles were characterized by scanning electron microscopy, X-ray powder diffraction, vibrating sample magnetometry, and zeta potential measurement. Response surface methodology (RSM) was employed to study the effects of the three most important parameters on encapsulation efficiency, namely DOX and Chr weight (2-18 mg), ε -CL weight (0.6-3.8 g), and sonication time (15-75s). The optimum encapsulation conditions were: 11.2 mg for DOX and Chr weight, 3.75 g for ε -CL, and 48.15 s for sonication time. The highest encapsulation efficiency in these conditions predicted by the equation is 95.68% and the release profile was controlled. There is potential for the application of Fe3O4- PCL-PEG4000 magnetic nanoparticles for biomedical purposes. [ABSTRACT FROM AUTHOR]

Nowadays, nanofibers have various applications in the field of medical biology including drug delivery systems (DDSs) and tissue engineering. Many methods have been developed to produce drug release polymers; the most important and applicable of which is known as electrospinning. In this method, the nanoscale and microscale fibers are used as the functional polymers in the DDSs. A variety of electrospinning methods can be used for delivery systems and tissue engineering. The nanofibers loaded with anticancer drugs have attracted a lot of attention in the last decade. Electrospun parameters include voltage, feed rate, rotary collector, pipette or needle hole diameter, the distance between nozzle tip to collector plate, viscosity and molecular weight of the polymer, surface tension, solubility of polymer, soluble electrical conductivity, dielectric constant, and evaporability of the solution; all could be manipulated to regulate the drug release rate in order via changing the diameter of the nanofibers. In addition to directly loading the drug on nanofibers, the nanoparticles are also used to improve the drug efficacy and reduce the required dose, especially in the case of harmful drugs. Depending on the need, various nanoparticles and nanocarriers are being applied along with the drug. Nanocarriers such as viruses, micelles, and liposomes function highly specific since they carry specific ligands on their surface. Magnetic nanoparticles also have a great therapeutic effect on cancer cells when exposed to heat and magnetic fields. Carbon nanoparticles, such as graphene and graphene oxide, due to their layering, can pass through the cell membrane and deliver the drug to the intracellular space. [ABSTRACT FROM AUTHOR]

Biodegradable polymeric micelles have potential therapeutic applications; nevertheless, preparing micelles of a specific diameter and uniform size distribution is a challenge. Micelles were formed from the copolymer of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) and the effect of PCEC molecular weight, PCL/PEG ratio, solvent-water miscibility, solvent concentration on particle size, polydispersity index and zeta potential of micelles were also investigated. The average particle sizes of the PCEC micelles ranged between 225–959 and 232–1211 nm for micelles prepared with acetone and dimethylformamide, respectively. The encapsulation efficiency is 78.98%. These results indicate that PCEC micelles can be used as drug carriers in controlled delivery systems. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder disease, disturbing people's normal life. Syringin was mentioned to antagonize Amyloid-β (Aβ)-induced neurotoxicity. However, the action mechanism is still not fully elucidated. This study aimed to explore a molecular mechanism of syringin in defending Aβ-induced neurotoxicity. SK-N-SH and SK-N-BE cells were treated with amyloid β-protein fragment 25–35 (Aβ25–35) to induce cell neurotoxicity. The injury effects were distinguished by assessing cell viability and cell apoptosis using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of Cleaved-caspase3 (Cleaved-casp3), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and BH3 interacting domain death agonist (BID) at the protein level was determined by western blot. The expression of miR-124-3p and BID was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-124-3p and BID was predicted by the online database starBase and confirmed by dual-luciferase reporter assay plus RNA pull-down assay. Aβ25–35 treatment inhibited cell viability and induced cell apoptosis, while the addition of syringin recovered cell viability and suppressed cell apoptosis. MiR-124-3p was significantly downregulated in Aβ25–35-treated SK-N-SH and SK-N-BE cells, and BID was upregulated. Nevertheless, the addition of syringin reversed their expression. BID was a target of miR-124-3p, and its downregulation partly prevented Aβ25–35-induced injuries. Syringin protected against Aβ25–35-induced neurotoxicity by enhancing miR-124-3p expression and weakening BID expression, and syringin strengthened the expression of miR-124-3p to diminish BID level. Syringin ameliorated Aβ25–35-induced neurotoxicity in SK-N-SH and SK-N-BE cells by regulating miR-124-3p/BID pathway, which could be a novel theoretical basis for syringin to treat AD. [ABSTRACT FROM AUTHOR]

Background: Phototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement. Results: Near-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO2 on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT. Conclusion: This study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy. [ABSTRACT FROM AUTHOR]

The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is one of the most common extracranial solid tumors of childhood and accounts for 15% of cancer deaths. Even with the multimodality treatment protocols, the advanced-stage tumor overall 5-year survival rate is less than 50%. Therefore, novel drug therapy targeting cellular signal transduction pathways regulating the apoptotic cascade may be important for the treatment of drug-resistant NB. In our previous studies, we have demonstrated that 5 μM sodium orthovanadate (SOV) induced the apoptosis of SH-SY5Y cells. 17-Allylamino-demethoxygeldanamycin (17-AAG) is a geldanamycin- (GA-) derived heat shock protein 90 (Hsp90) inhibitor, and it has been shown to have potent antitumor activity in head and neck cancers. However, the effect of 17-AAG on the apoptosis of NB cells has not been reported. Therefore, the purpose of this study was to determine the effects of 17-AAG and SOV on the growth and invasion of SH-SY5Y cells in vitro and explore the related mechanism. In this study, we first investigated the antiviability effect of 17-AAG on SH-SY5Y cells, then studied the cell apoptosis and invasion influenced by 17-AAG and SOV, and assessed the role of PIWI-Like2 (PIWIL2) and piRNA-PIWI signaling in it. The results showed that 5 μM 17-AAG inhibited cell growth and viability and induced apoptosis in SH-SY5Y cells. Both 17-AAG and SOV reduced the level of PIWIL2 and Bcl-xl proteins and inhibited the invasion of SH-SY5Y cells. In addition, the combined use of the two drugs had greater effect than the single use of any drug. [ABSTRACT FROM AUTHOR]

Activation Induced cytidine Deaminase (AID) is an essential enzyme of the adaptive immune system. Its canonical activity is restricted to B lymphocytes, playing an essential role in the diversification of antibodies by enhancing specificity and changing affinity. This is possible through its DNA deaminase function, leading to mutations in DNA. In the last decade, AID has been assigned an additional function: that of a powerful DNA demethylator. Adverse cellular conditions such as chronic inflammation can lead to its deregulation and overexpression. It is an important driver of B-cell lymphoma due to its natural ability to modify DNA through deamination, leading to mutations and epigenetic changes. However, the deregulation of AID is not restricted to lymphoid cells. Recent findings have provided new insights into the role that this protein plays in the development of non-lymphoid cancers, with some research shedding light on novel AID-driven mechanisms of cellular transformation. In this review, we provide an updated narrative of the normal physiological functions of AID. Additionally, we review and discuss the recent research studies that have implicated AID in carcinogenesis in varying tissue types including lymphoid and non-lymphoid cancers. We review the mechanisms, whereby AID promotes carcinogenesis and highlight important areas of future research. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase 13 (MMP13) is indispensable for normal skeletal development and is also a principal proteinase responsible for articular joint pathologies. MMP13 mRNA level needs to be tightly regulated in both positive and negative manners to achieve normal development and also to prevent joint destruction. We showed previously that Kruppel-like factor 4 (KLF4) strongly induces the expression of members of the MMP family of genes including that for MMP13 in cultured chondrocytes. Through expression-based screening of approximately 400 compounds, we identified several that efficiently downregulated MMP13 gene expression induced by KLF4. Compounds grouped as topoisomerase inhibitors (transcriptional inhibitors) downregulated MMP13 expression levels, which proved the validity of our screening method. In this screening, trichostatin A (TSA) was identified as one of the most potent repressors. Mechanistically, increased MMP13 mRNA levels induced by KLF4 were not mainly caused by increased rates of RNA polymerase II–mediated MMP13 transcription, but arose from escaping mRNA decay. TSA treatment almost completely blunted the effect of KLF4. Importantly, KLF4 was detected in chondrocytes at the joint destruction sites in a rodent model of osteoarthritis. Our results partially explain how KLF4 regulates numerous proteinase gene expressions simultaneously in chondrocytes. Also, these observations suggest that modulation of KLF4 activity or expression could be a novel therapeutic target for osteoarthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Myocardial inflammation mediated by toll-like receptor 4 (TLR4) plays an active role in myocardial ischemia/reperfusion (I/R) injury. Studies show that heat shock protein 90 (HSP90) is involved in ischemic postconditioning (IPostC) cardioprotection. This study investigates the roles of TLR4 and HSP90 in IPostC. METHODS: Rats were subjected to 30 min ischemia, then 2 h reperfusion. IPostC was applied by three cycles of 30 s reperfusion, then 30 s reocclusion at reperfusion onset. Sixty rats were randomly divided into four groups: sham, I/R, IPostC, and geldanamycin (GA, HSP90 inhibitor, 1 mg/kg) plus IPostC (IPostC + GA). RESULTS: IPostC significantly reduced I/R-induced infarct size (40.2±2.1% versus 28.4±2.4%; P < 0.05); the release of cardiac Troponin T, creatine kinase-MB, and lactate dehydrogenase (191.5±3.1 versus 140.6±3.3 pg/ml, 3394.6±132.7 versus 2880.7±125.5 pg/ml, 2686.2±98.6 versus 1848.8±90.1 pg/ml, respectively; P < 0.05); and cardiomyocyte apoptosis (40.3±2.2% versus 27.0±1.6%; P < 0.05). Further, local and circulating IL-1β, IL-6, TNF-α, and ICAM-1 levels decreased; TLR4 expression and nuclear factor-KB (NF-κB) signaling decreased; and cardiac HSP90 expression increased. Blocking HSP90 function with GA inhibited IPostC protection and anti-inflammation, suggesting that IPostC has a HSP90-dependent anti-inflammatory effect. CONCLUSION: HSP90 may play a role in IPostC-mediated cardioprotection by inhibiting TLR4 activation, local and systemic inflammation, and NF-kB signaling. [ABSTRACT FROM AUTHOR]

Nanotechnology empowered localized cancer chemotherapy has indicated a promising performance for targeting and controlled release of anticancer agents over a period of time to eliminate local‐regional recurrence of cancers and also to improve the tissue regeneration during/after treatment. Electrospun nanofiber‐based implantable drug‐delivery systems have been established as one of the most effective approaches for localized cancer treatment, allowing the on‐site delivery of anticancer agents and reducing systemic toxicities and side effects to normal cells. The present review aimed to summarize the latest cutting‐edge research on applications of electrospun‐based systems for local chemotherapy. Meantime, in vitro and in vivo studies conducted using various anticancer agents along with the capability of electrospun nanofibers for combinatorial/synergistic chemotherapy as well as existing challenges and the potential dramatic advances in applying this pioneering approach for clinical transition in localized treatments of cancer is also discussed. [ABSTRACT FROM AUTHOR]

The present study evaluated the effect of combining inhibitors (17-AAG) of heat shock protein 90 (HSP90) and autophagy (3-MA) on apoptosis using an incomplete thermal ablation animal model. A total of 28 orthotopic mice with hepatocellular carcinoma were randomly divided into 4 groups to receive different drug interventions. Following palliative laser ablation, changes in autophagy, apoptosis and Akt/mTOR expression levels were assessed in tumors. Compared with the controls, the 17-AAG-treated mice exhibited significantly decreased expression levels of phosphorylated (p)-Akt and p-mTOR with enhanced autophagy and apoptosis; no marked increases in the expression levels of p-Akt and p-mTOR were observed in the 3-MA-treated mice, with no significant changes in autophagy; however, apoptosis was enhanced. No significant decreases in p-Akt and p-mTOR or any increase in autophagy were observed in the mice receiving a combination of 17-AAG and 3-MA, but they did exhibit a marked increase in apoptosis. Compared with 17-AAG alone, the combination of 17-AAG and 3-MA resulted in a marked increase in apoptosis without enhanced autophagy. In the incomplete ablation model, the effects of autophagy and apoptosis are antagonistic. The combined use of 17-AAG and 3-MA can significantly promote apoptosis and is worthy of further study. [ABSTRACT FROM AUTHOR]

Intimal hyperplasia (IH) is a pathologic process that leads to restenosis after treatment for peripheral arterial disease. Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein maturation. Activation of HSP90 results in increased cell migration and proliferation. 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) are low toxicity Food and Drug Association approved HSP90 inhibitors. The current study hypothesized that HSP90 inhibition was predicted to reduce vascular smooth muscle cell (VSMC) migration and proliferation. In addition, localized HSP90 inhibition may inhibit post-angioplasty IH formation. For proliferation, VSMCs were treated with serum-free media (SFM), 17-DMAG or 17-AAG. The selected proliferative agents were SFM, platelet derived growth factor (PDGF) or fibronectin. After three days, proliferation was measured. For migration, VSMCs were treated with SFM, 17-AAG or 17-DMAG with SFM, PDGF or fibronectin as chemoattractants. Balloon injury to the carotid artery was performed in rats. The groups included in the present study were the control, saline control, 17-DMAG in 20% pluronic gel delivered topically to the adventitia or intraluminal delivery of 17-DMAG. After 14 days, arteries were fixed and sectioned for morphometric analysis. Data was analyzed using ANOVA or a student's t-test. P<0.05 was considered to indicate a statistically significant difference. The results revealed that 17-AAG and 17-DMAG had no effect on cell viability. PDGF and fibronectin also increased VSMC proliferation and migration. Furthermore, both 17-AAG and 17-DMAG decreased cell migration and proliferation in all agonists. Topical adventitial treatment with 17-DMAG after balloon arterial injury reduced IH. HSP90 inhibitors suppressed VSMC proliferation and migration without affecting cell viability. Topical treatment with a HSP90 inhibitor (DMAG) decreased IH formation after arterial injury. It was concluded that 17-DMAG may be utilized as an effective therapy to prevent restenosis after revascularization. [ABSTRACT FROM AUTHOR]

Poly-ε-caprolactone (PCL) has been the subject of extensive research in the past few years. It is widely explored in drug delivery, where the development of nanomedicines for cancer, one of the major public health concerns nowadays, has not been the exception. As a biocompatible, biodegradable and bioresorbable polymer, PCL has also found plenty of uses in the form of microparticles and scaffolds; so is the main objective of the present review to emphasize its potential and present its properties along with applications in the pharmaceutical and biomedical area with a special focus on nanomedicine in cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most frequent causes of cancer related death worldwide, and despite the significant advances in therapeutic approaches, a significant proportion of patients succumb to metastasis and tumor recurrence. Breast cancer is an immunogenic cancer, and therefore, immunotherapy is considered a major therapeutic strategy. The survival rate has been increased significantly in HER2+ breast cancers after immunotherapy by monoclonal antibodies alone, or combined with chemical anti-cancer agents. Moreover, in triple negative breast cancer (TNBC), a number of novel agents called immune checkpoint inhibitors have shown optimal efficacy. The major hindrance in cancer immunotherapy is frequent development of resistance and cancer remission. cGAS-STING pathway has a key role in anti-cancer immunity as its downstream signals especially type I interferon (IFN) acts as a link between innate and adaptive immunity. Considering the roles of type I IFN in enhancing dendritic cells activity, promoting the functions of CD8 + T cells, and protecting the effector cells against apoptosis, the induction of cGAS-STING pathway demonstrated promising therapeutic effects against breast cancer, especially in triple negative breast cancers. In this review, we discuss the latest findings and the recent advances regarding the role of cGAS-STING pathway and its activation in breast cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycyclic aromatic hydrocarbons (PAHs) are one of the main pollutants generated by the refining and use of oil. To search bioremediation alternatives for these compounds, mainly in situ, considering the biotic and abiotic variables that affect the contaminated sites is determinant for the success of bioremediation techniques. In this study, bioremediation strategies were evaluated in situ, including biostimulation and bioaugmentation for 16 priority PAHs present in activated sludge farms. B. vietnamiensis G4 was used as a biodegradation agent for bioaugmentation tests. The analyses occurred for 12 months, and temperature and humidity were measured to verify the effects of these factors on the biodegradation. We used the technique GC-MS to evaluate and quantify the degradation of PAHs over the time of the experiment. Of the four treatments applied, bioaugmentation with quarterly application proved to be the best strategy, showing the degradation of compounds of high (34.4% annual average) and low (21.9% annual average) molecular weight. A high degradation rate for high molecular weight compounds demonstrates that this technique can be successfully applied in bioremediation of areas with compounds considered toxic and stable in nature, contributing to the mitigation of impacts generated by PAHs., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Induction of protein synthesis by the external delivery of in-vitro transcription-messenger RNA (IVT-mRNA) has been a useful approach in the realm of cell biology, disease treatment, reprogramming of cells, and vaccine design. Therefore, the development of new formulations for protection of mRNA against nucleases is required to maintain its activity in-vivo. It was the aim of the present study to investigate the uptake, toxicity, transfection efficiency as well as phenotypic consequences of a nanoparticle (NP) in cell culture. NP consists of poly D, L-lactide-co-glycolide (PLGA) and polyethyleneimine (PEI) for delivery of in-vitro transcription-messenger RNA (IVT- mRNA) encoded green fluorescent protein (GFP) in human monocyte-derived dendritic cells (moDCs). Nanoparticles that were synthesized and encapsulated with synthetic GFP mRNA, exhibited size distribution in this formulation, with mean particle sizes ranging between 415 and 615 nm. Zeta potential was positive (above 12-13 mV) and the encapsulation efficiency exceeded 73.5%. Our results demonstrated that PLGA/PEI NPs encapsulation of GFP mRNA had no toxic effect on immature monocytederived dendritic cells and was capable of delivering of IVT-mRNA into moDCs and was highly effective. The expression of GFP protein 48 h after transfection was confirmed by flow cytometry, microscopic examination and western blotting assay. This NP can make a way to target moDCs to express a variety of antigens by IVT- mRNA. The present study introduced the PLGA/PEI NP, which provided effective delivery of IVT-mRNA that encodes the GFP protein. [ABSTRACT FROM AUTHOR]

Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library. Our inhibitory compound named 8m inhibited Hsp90 and PI3Kα with an IC50 value of 38.6 nM and 48.4 nM, respectively; it displayed improved cellular activity which could effectively induce cell cycle arrest and apoptosis in melanoma cells and lead to the inhibition of cell proliferation, colony formation, migration and invasion. Our results demonstrated 8m to be a promising lead compound for further therapeutic potential assessment of Hsp90/PI3Kα dual inhibitors in melanoma targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Adrenocortical carcinoma (ACC) is a rare tumor entity with restricted therapeutic opportunities. HSP90 (Heat Shock Protein 90) chaperone activity is fundamental for cell survival and contributes to different oncogenic signaling pathways. Indeed, agents targeting HSP90 function have shown therapeutic efficacy in several cancer types. We have examined the expression of HSP90 in different adrenal tumors and evaluated the use of HSP90 inhibitors in vitro as possible therapy for ACC. Methods: Immunohistochemical expression of HSP90 isoforms was investigated in different adrenocortical tumors and associated with clinical features. Additionally, a panel of N-terminal (17-allylamino-17-demethoxygeldanamycin (17-AAG), luminespib, and ganetespib) and C-terminal (novobiocin and silibinin) HSP90 inhibitors were tested on various ACC cell lines. Results: Within adrenocortical tumors, ACC samples exhibited the highest expression of HSP90β. Within a cohort of ACC patients, HSP90β expression levels were inversely correlated with recurrence-free and overall survival. In functional assays, among five different compounds tested luminespib and ganetespib induced a significant decrease in cell viability in single as well as in combined treatments with compounds of the clinically used EDP-M scheme (etoposide, doxorubicin, cisplatin, mitotane). Inhibition of cell viability correlated furthermore with a decrease in proliferation, in cell migration and an increase in apoptosis. Moreover, analysis of cancer pathways indicated a modulation of the ERK1/2—and AKT—pathways by luminespib and ganetespib treatment. Conclusions: Our findings emphasize HSP90 as a marker with prognostic impact and promising target with N-terminal HSP90 inhibitors as drugs with potential therapeutic efficacy toward ACC. [ABSTRACT FROM AUTHOR]

TYK2-rearrangements have recently been identified in high-risk acute lymphoblastic leukemia (HR-ALL) cases and are associated with poor outcome. Current understanding of the leukemogenic potential and therapeutic targetability of activating TYK2 alterations in the ALL setting is unclear, thus further investigations are warranted. Consequently, we developed in vitro, and for the first time, in vivo models of B-cell ALL from a patient harboring the MYB-TYK2 fusion gene. These models revealed JAK/STAT signaling activation and the oncogenic potential of the MYB-TYK2 fusion gene in isolation. High throughput screening identified the HDAC inhibitor, vorinostat and the HSP90 inhibitor, tanespimycin plus the JAK inhibitor, cerdulatinib as the most effective agents against cells expressing the MYB-TYK2 alteration. Evaluation of vorinostat and cerdulatinib in pre-clinical models of MYB-TYK2-rearranged ALL demonstrated that both drugs exhibited anti-leukemic effects and reduced the disease burden in treated mice. Importantly, these findings indicate that activating TYK2 alterations can function as driver oncogenes rather than passenger or secondary events in disease development. In addition, our data provide evidence for use of vorinostat and cerdulatinib in the treatment regimens of patients with this rare yet aggressive type of high-risk ALL that warrants further investigation in the clinical setting., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Magnetic carbon nanotubes (MCNTs) have been widely studied for their potential applications in medicine, diagnosis, cell biology, analytical chemistry, and environmental technology. Introduction of MCNTs paved the way for the emergence of new approaches in nanobiotechnology and biomedicine as a result of their multifarious properties embedded within either the carbon nanotubes (CNTs) or magnetic parts. Numerous preparation techniques exists for functionalizing CNTs with magnetic nanoparticles, and these versatile strategies lay the ground for the generation of novel and versatile systems which are applicable to many industries and biological areas. Here, we review and discuss the recent papers dealing with MCNTs and their application in biomedical and industrial fields. [ABSTRACT FROM AUTHOR]

The current long-term treatment for leishmaniasis causes severe side effects and resistance in some cases. An evaluation of the anti-leishmanial potential of an HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated its potent effect against Leishmania spp. in vitro and in vivo. We have previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an IC50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As this compound presents low solubility and high toxicity in human clinical trials, we prepared an inclusion complex containing hydroxypropyl-β-cyclodextrin and 17-AAG (17-AAG:HPβCD) to improve its solubility. This complex was characterized by scanning electron microscopy, and X-ray diffraction. Liposomes-containing 17-AAG:HPβCD was prepared and evaluated for encapsulation efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta potential, before and after accelerated and long-term stability testing. An evaluation of leishmanicidal activity against promastigotes and intracellular amastigotes of L. (L) amazonensis was also performed. The characterization techniques utilized confirmed the formation of the inclusion complex, HPβCD:17-AAG, with a resulting 33-fold-enhancement in compound water solubility. Stability studies revealed that 17-AAG:HPβCD-loaded liposomes were smaller than 200 nm, with 99% EE. Stability testing detected no alterations in PDI that was 0.295, pH 7.63, and zeta potential +22.6, suggesting liposome stability, and suitability for evaluating leishmanicidal activity. Treatment of infected macrophages with 0.006 nM of 17-AAG:HPβCD or 17-AAG:HPβCD-loaded liposomes resulted in almost complete amastigote clearance inside macrophages after 48 h. This reduction is similar to the one observed in infected macrophages treated with 2 μM amphotericin B. Our results showed that nanotechnology and drug delivery systems could be used to increase the antileishmanial efficacy and potency of 17-AAG in vitro , while also resulting in reduced toxicity that indicates these formulations may represent a potential therapeutic strategy against leishmaniasis. [ABSTRACT FROM AUTHOR]

Due to the high rate of drug resistance among malignant melanoma cases, it seems necessary to introduce an efficient pharmaceutical approach to melanoma treatment. For this purpose, Curcumin (Cur) and Chrysin (Chr), two natural anti-cancers, were co-encapsulated in PLGA-PEG nanoparticles (NPs), characterized by DLS, FTIR and FE-SEM and investigated for their effects on MMPs, TIMPs and TERT genes expression in C57B16 mice bearing B16F10 melanoma tumours. The results showed that the expression of MMP-9, MMP-2 and TERT genes were significantly decreased in all treated groups compared to the control. This reduction had the highest amount in CurChr NPs group and then CurChr group for each three genes. Likewise, the expression of TIMP-1 and TIMP-2 genes was significantly increased in all treated groups, compared to the control. Combination groups showed the highest rise in expression of these two genes and the observed increase was greater in nano groups. Moreover, the highest melanoma tumour growth inhibition was detected for CurChr NPs, followed by CurChr = Cur NPs > Cur > Chr NP > Chr. Overall, it is speculated that the nano-combination of Cur and Chr into polymeric NPs with a one-step fabricated co-delivery system may be a promising and convenient approach to improve their efficiency in melanoma cancer therapy. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC)-based cell therapy can provide opportunities for the treatment of various diseases. However, when used in vivo, these cells should be labelled and monitored by a non-invasive method during delivery to the desired locations within the body. This study describes a biomimicry method that effectively labels human Wharton's jelly-derived MSCs (hWJ-MSCs) with a photoacoustics (PA) contrast agent, gold nanorods (GNRs), without the need for transfection agents (TAs). In this method for cell labelling, the hWJ-MSCs were co-incubated with non-adherent cells isolated from fresh umbilical cord for 2 days immediately before incubation with GNRs. Next, hWJ-MSCs were labelled with the GNRs at a concentration of approximately 10 10 nanorads/mL (NR/mL) followed by transmission electron microscopy (TEM) and inductively coupled plasma mass spectroscopy (ICP-MS) to verify their labelling effectiveness. The GNRs-labelled MSCs prepared by this method had an intracellular gold (Au) concentration of 3.4 ± 0.4 pg/cell, which is an acceptable amount for cell labelling., (© 2021 John Wiley & Sons Ltd.)

Nanoparticle-based targeted drug delivery has the potential for rendering silibinin specifically at the favorite site using an external magnetic field. Also, it can circumvent the pitfalls of poor solubility. For this purpose, silibinin-loaded magnetic nanoparticles are fabricated, characterized and evaluated cytotoxicity and hTERT gene expression in A549 lung cancer cell line. silibinin-loaded PLGA-PEG-Fe3O4had dose- and time-dependent cytotoxicity than pure silibinin. Additionally, hTERT expression is more efficiently reduced with increasing concentrations of nanosilibinin than pure silibinin. The present study indicates that PLGA-PEG-Fe3O4nanoparticles, as an effective targeted carrier, can make a promising horizon in targeted lung cancer therapy. [ABSTRACT FROM PUBLISHER]