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Immune checkpoint blockade (ICB) with anti‐CD47 antibodies (aCD47) is a promising therapeutic approach that has the potential to revolutionize the treatment of acute myeloid leukemia (AML). However, the low immune response rate and high systemic hematotoxicity remain substantial barriers to its success in clinical AML treatment. A synthetic protein nanogel formulation of aCD47 and resiquimod (R848) (termed CR‐TNG) is developed that targets TIM‐3 on the surface of leukemia cells. Upon intravenous injection, the CR‐TNG efficiently conjugates onto the blood‐circulating leukemia cells and migrates toward the bone marrow (BM) by exploiting the natural BM homing capability of leukemia cells. CR‐TNG releases aCD47 and R848 in a bone marrow hypoxic microenvironment, which significantly induces immunosuppression and enhances the anti‐leukemia immune response by activating macrophage “eat me” signaling and priming myeloid macrophages in the BM niche. These findings provide a leukemia cell‐hitchhiking drug delivery strategy that addresses both systemic hematotoxicity and low immune response rate in AML. [ABSTRACT FROM AUTHOR]

[Display omitted] Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy. [ABSTRACT FROM AUTHOR]

AbstractThis study investigates drug-loaded liposomes designed for controlled release under ionizing radiation to refine cancer treatment precision. Liposomes as carriers enable targeted chemotherapy delivery, reducing healthy tissue damage risk. Liposomes containing poly- or mono-unsaturated fatty acids and various sensitizing agents were assessed for responsiveness to UV light and γ photon irradiation including rose bengal (RB), protoporphyrin IX (PPIX), verteporfin (VP), cercosporin (CERC) and hypericin (HYP). Carboxyfluorescein (CF) was used as a surrogate for drug release measurements. VP and PPIX induced rapid drug release and lipid peroxidation under UV light, while RB prompted quick drug release under UV light and a modest immediate release under γ irradiation, eventually reaching full release a few hours after irradiation, demonstrating dose-dependent effects. Smaller liposomes displayed accelerated release, emphasizing size-dependent kinetics. In vitro analyses evaluated radiosensitizing effects of RB-loaded liposomes. Clonogenic assays indicated that RB-filled liposomes had minimal direct radiobiological effects but increased indirect radiation damage, as shown by the curvature of the cell survival curve. Our study sheds light on factors influencing liposomal drug release under ionizing radiation, spotlighting RB as a promising radiosensitizer requiring further investigation for cancer therapy potential. [ABSTRACT FROM AUTHOR]

Significant advances have been made in materials for biomedical applications, including tissue engineering, bioimaging, cancer treatment, etc. In the past few decades, nanostructure-mediated therapeutic strategies have been developed to improve drug delivery, targeted therapy, and diagnosis, maximizing therapeutic effectiveness while reducing systemic toxicity and side effects by exploiting the complicated interactions between the materials and the cell and tissue microenvironments. This review briefly introduces the differences between the cells and tissues of tumour or normal cells. We summarize recent advances in tumour microenvironment-mediated therapeutic strategies using nanostructured materials. We then comprehensively discuss strategies for fabricating nanostructures with cancer cell-specific cytotoxicity by precisely controlling their composition, particle size, shape, structure, surface functionalization, and external energy stimulation. Finally, we present perspectives on the challenges and future opportunities of nanotechnology-based toxicity strategies in tumour therapy. [ABSTRACT FROM AUTHOR]

Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a significant global health challenge, with limited therapeutic options for patients with KRAS-mutated tumors. Herein, a copper-based metal-organic framework (Cu-MOF) was applied as a novel cuproptosis-mediated nanoplatform for lung cancer therapy. Cu-MOF would disassemble and liberate copper ions under the acidic microenvironment of lysosomes of cancer cells, initiating a cascade of cellular events. The released copper ions catalyzes the Fenton reaction, generating hydroxyl radicals that induce oxidative damage, leading to cytoskeletal disruption and activation of caspase-3, ultimately triggering apoptosis. Simultaneously, with the mediation of the key regulatory factor FDX1, we found that the copper ions binding to the mitochondrial protein DLAT could result in the loss of iron-sulfur cluster proteins and aggregation of lipoylated proteins, which culminated in proteotoxic stress-induced cuproptosis. The pronounced anti-tumor effects of Cu-MOF with apoptosis and cuproptosis were confirmed both in vitro and in vivo experiments. Such dual induction of apoptosis and cuproptosis by Cu-MOF presents a promising therapeutic strategy for NSCLC, particularly for KRAS-mutated tumors, and expands potential applications of Cu-based nanomateirals for other cancers. [ABSTRACT FROM AUTHOR]

Mucus is a hydrated, viscoelastic, and adhesive gel that lubricates and protects the body from pathogens; however, its protective function hinders drug/nanomedicine diffusion and treatment efficiency. Therefore, novel drug delivery strategies are required to overcome challenging mucosal barriers. Here, multi‐responsive nanogels (NGs) are developed and explored their interaction with mucus. Specific NG features (e.g., surface charge, temperature responsiveness, and redox response) are evaluated in a typical mucus‐associated environment (i.e., mucin proteins and high glutathione concentrations). The results demonstrate that biocompatibility and the capacity to deliver a protein through mucosal barriers in different in vitro and in vivo models highlight the importance of specific NG design elements. Disulfide bonds are highlighted as redox‐sensitive cross‐linkers within the NG structure as critical for drug delivery performance; they function as degradation points that enable NG degradation and subsequent drug release and anchoring points to adhere to mucin, thereby enhancing their residence time at the desired site of action. Additionally, it is confirmed that surface charges impact interactions with mucin; positively charged NGs exhibit improved interactions with mucin compared to negatively charged and neutral NGs. Overall, the findings underline the importance of redox response and surface charge in NG design for reaching efficient mucosal drug delivery. [ABSTRACT FROM AUTHOR]

DNA nanostructures have shown great potential in biomedical fields. However, the immune responses, especially the activation of the cGAS‐STING signaling (A‐cGSs), induced by DNA nanostructures, remain incompletely understood. Here, the ability of various DNA nanostructures from double‐stranded DNA (dsDNA), single‐stranded tiles (SSTs) to DNA origami is investigated on A‐cGSs. Unlike natural dsDNA which triggers potent A‐cGSs, the structural interconnectivity of various DNA configurations can substantially reduce the occurrence of A‐cGSs, irrespective of their form, dimensions, and conformation. However, wireframe DNA nanostructures can activate the cGAS‐STING signaling, suggesting that decreasing A‐cGSs is dsDNA compactness‐dependent. Based on this, a reconfigurable DNA Origami Domino Array (DODA) is used to systematically interrogate how dsDNA influences the A‐cGSs and demonstrates that the length, number, and space of dsDNA array coordinately influence the activation level of cGAS‐STING signaling, realizing a regulation of innate immune response. The above data and findings enhance the understanding of how DNA nanostructures affect cellular innate immune responses and new insights into the modulation of innate immune responses by DNA nanomedicine. [ABSTRACT FROM AUTHOR]

Sulforaphane is well-known for its anti-cancer properties particularly against breast, skin and prostate cancers. High sensitivity of sulforaphane to oxygen, heat, and alkaline conditions, as well as its poor oral bioavailability and water instability limit its use in medicine. In this study, we aim to overcome the prementioned limitations by encapsulating sulforaphane within a lipid-based drug delivery system, known as emulsome, and investigate the anti-cancer features of the attained formulation.The stability and dispersity of the formulation were assessed sequentially by zeta sizer, scanning electron microscopy and confocal laser scanning microscopy. Cell culture studies were performed to evaluate the anticancer activity of the formulation.Sulforaphane-loaded emulsomes with an average particle size of 246.0±14.1 nm, an average zeta potential of −23.5±2.4 mV and a polydispersity index of around 0.38 were produced. Encapsulations up to 0.036 mg/mL sulforaphane concentration was achieved. When MCF7 breast cancer cells were treated with sulforaphane-loaded emulsomes, a significant decrease was observed in proliferation of the cells along 72 h. In control group, emulsomes were found safe as tested at same concentrations on MCF-10a healthy cells. Applied as dissolved in DMSO, free sulforaphane with an IC50 value of 1.2 µM was more effective against MCF7 cells than sulforaphane-loaded emulsome formulation having a IC50 value 21.1 µM.Sulforaphane-loaded emulsomes were obtained as stable, moderately disperse suspensions. Delivery of the bioactive compound into the cells were achieved. Yet, its biological activity remained behind its free form. [ABSTRACT FROM AUTHOR]

Purpose: The antibacterial properties of silver nanoparticles (AgNPs) are extensively identified. In large quantities, they might be harmful. So many fields of nanotechnology have shown a great deal of interest in the development of an environmentally friendly, efficient method for synthesizing metal nanoparticles. Because of its antibacterial and antifungal properties toward a wide range of microbes, chitosan silver nanoparticles (AgNPs@Cs) constitute a newly developing class of bio-nanostructured hybrid materials. Furthermore, the use of photothermal therapy (PTT) has been suggested as a means of elimination of germs. These light-stimulated treatments are minimally invasive and have a few side effects. In the present work, the antibacterial effect of AgNPs at low concentrations; prepared by chemical and green methods as antimicrobial and photothermal agents in photothermal therapy; with laser irradiation were explored as combined treatment against MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Methods: Silver nanoparticles were produced in two ways. First, by sodium borohydrides, second, by chitosan (as a natural eco-friendly reducing, and capping agent). The nanostructure of AgNPs and AgNPs@Cs was confirmed by UV–visible spectrometer, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIRs), and direct light scattering (DLS). The antibacterial activity of the prepared nanoparticles and the laser irradiation was tested against three bacterial species of zoonotic importance; MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae; and was evaluated by measuring their minimum inhibitory concentrations (MIC). Results: Silver nanoparticles produced by the two methods had spherical shapes with nearly the same particle size. The analysis of DLS showed that AgNPs were very stable with zeta potential − 28.8 mv, and 47.7 mv by chemical and chitosan synthesis, respectively. Furthermore, AgNPs@Cs showed higher antibacterial activity toward the tested bacterial species than AgNPs by chemical method. Additionally, the bacterial viability using photothermal laser therapy was reduced compared to laser and AgNPs alone. The bactericidal activities were higher when laser diode was coupled with AgNPs@Cs than by chemical reduction. Conclusion: The laser combined treatment had a higher antimicrobial effect than AgNPs alone or laser irradiation alone. [ABSTRACT FROM AUTHOR]

Background: Skin cancer continues to be an imperative global health issue, urging continuous exploration of treatment methodologies. Conventional treatments for skin cancer include surgical interventions, immunotherapy, targeted therapy, chemotherapy, and radiation therapy. However, these methods often present obstacles like treatment resistance, systemic toxicity, limited effectiveness in advanced stages, infection risk, pain, long recovery, and impact on healthy tissue. Nanomedicine holds promise by facilitating precise drug administration, early detection, and heightened therapeutic efficiency via targeted and localized delivery systems. The integration of nanomedicine into skin cancer alleviation therapies demonstrates optimistic outcomes, including refined drug delivery, augmented bioavailability, minimized adverse effects, and potential theranostic applications. Recent breakthroughs in nanomedicine have propelled advancements in skin cancer treatment, showing significant potential in transforming the treatment paradigm. The presents review provides comprehensive aspects of existing skin cancer treatments and their challenges, spotlighting recent breakthroughs propelled by nanomedicine. Short conclusion: This abstract delineates the present landscape of skin cancer treatments, underscores their constraints, and highlights recent strides in nanomedicine that have the potential to transform the paradigm of skin cancer treatment, ultimately elevating patient prognosis. Importantly, the present review emphasizes substantial challenges that hinder the clinical translation of nanomedicines and suggests possible remedies to surpass them. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) still prevails and continues to increase indiscriminately throughout the 21st century, and is thus responsible for the depreciating quality of health and associated sectors. AD is a progressive neurodegenerative disorder marked by a significant amassment of beta-amyloid plaques and neurofibrillary tangles near the hippocampus, leading to the consequent loss of cognitive abilities. Conventionally, amyloid and tau hypotheses have been established as the most prominent in providing detailed insight into the disease pathogenesis and revealing the associative biomarkers intricately involved in AD progression. Nanotheranostic deliberates rational thought toward designing efficacious nanosystems and strategic endeavors for AD diagnosis and therapeutic implications. The exceeding advancements in this field enable the scientific community to envisage and conceptualize pharmacokinetic monitoring of the drug, sustained and targeted drug delivery responses, fabrication of anti-amyloid therapeutics, and enhanced accumulation of the targeted drug across the blood–brain barrier (BBB), thus giving an optimistic approach towards personalized and precision medicine. Current methods idealized on the design and bioengineering of an array of nanoparticulate systems offer higher affinity towards neurocapillary endothelial cells and the BBB. They have recently attracted intriguing attention to the early diagnostic and therapeutic measures taken to manage the progression of the disease. In this article, we tend to furnish a comprehensive outlook, the detailed mechanism of conventional AD pathogenesis, and new findings. We also summarize the shortcomings in diagnostic, prognostic, and therapeutic approaches undertaken to alleviate AD, thus providing a unique window towards nanotheranostic advancements without disregarding potential drawbacks, side effects, and safety concerns. [ABSTRACT FROM AUTHOR]

Adipose tissue-derived adult stem (ADAS) cells and extracellular vesicle (EV) therapy offer promising avenues for treating neurodegenerative diseases due to their accessibility and potential for autologous cell transplantation. However, the clinical application of ADAS cells or EVs is limited by the challenge of precisely identifying them in specific regions of interest. This study compares two superparamagnetic iron oxide nanoparticles, differing mainly in size, to determine their efficacy for allowing non-invasive ADAS tracking via MRI/MPI and indirect labeling of EVs. We compared a USPIO (about 5 nm) with an SPIO (Resovist®, about 70 nm). A physicochemical characterization of nanoparticles was conducted using DLS, TEM, MRI, and MPI. ADAS cells were labeled with the two nanoparticles, and their viability was assessed via MTT assay. MRI detected labeled cells, while TEM and Prussian Blue staining were employed to confirm cell uptake. The results revealed that Resovist® exhibited higher transversal relaxivity value than USPIO and, consequently, allows for detection with higher sensitivity by MRI. A 200 µgFe/mL concentration was identified as optimal for ADAS labeling. MPI detected only Resovist®. The findings suggest that Resovist® may offer enhanced detection of ADAS cells and EVs, making it suitable for multimodal imaging. Preliminary results obtained by extracting EVs from ADAS cells labeled with Resovist® indicate that EVs retain the nanoparticles, paving the way to an efficient and multimodal detection of EVs. [ABSTRACT FROM AUTHOR]

The increasing incidence of breast cancers (BCs) in the world population and their complexity and high metastatic ability are serious concerns for healthcare systems. Despite the significant progress in medicine made in recent decades, the efficient treatment of invasive cancers still remains challenging. Chemotherapy, a fundamental systemic treatment method, is burdened with severe adverse effects, with efficacy limited by resistance development and risk of disease recurrence. Also, current diagnostic methods have certain drawbacks, attracting attention to the idea of developing novel, more sensitive detection and therapeutic modalities. It seems the solution for these issues can be provided by nanotechnology. Particularly, quantum dots (QDs) have been extensively evaluated as potential targeted drug delivery vehicles and, simultaneously, sensing and bioimaging probes. These fluorescent nanoparticles offer unlimited possibilities of surface modifications, allowing for the attachment of biomolecules, such as antibodies or proteins, and drug molecules, among others. In this work, we discuss the potential applicability of QDs in breast cancer diagnostics and treatment in light of the current knowledge. We begin with introducing the molecular and histopathological features of BCs, standard therapeutic regimens, and current diagnostic methods. Further, the features of QDs, along with their uptake, biodistribution patterns, and cytotoxicity, are described. Based on the reports published in recent years, we present the progress in research on possible QD use in improving BC diagnostics and treatment efficacy as chemotherapeutic delivery vehicles and photosensitizing agents, along with the stages of their development. We also address limitations and open questions regarding this topic. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) are the most clinically advanced drug delivery system for nucleic acid therapeutics, exemplified by the success of the COVID-19 mRNA vaccines. However, their clinical use is currently limited to hepatic diseases and vaccines due to their tendency to accumulate in the liver upon intravenous administration. To fully leverage their potential, it is essential to understand and address their liver tropism, while also developing strategies to enhance delivery to tissues beyond the liver. Ensuring that these therapeutics reach their target cells while avoiding off-target cells is essential for both their efficacy and safety. There are three potential targeting strategies—passive, active, and endogenous—which can be used individually or in combination to target nonhepatic tissues. In this review, we delve into the recent advancements in LNP engineering for delivering nucleic acid beyond the liver. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery (TDD) has gained clinical approval over several decades, with extensive research dedicated to novel drug and device development. Despite notable research progress, the market adoption of TDD devices has not met anticipated levels, with oral administration and injection remaining predominant delivery methods. To maximize the potential of TDD, we identify bottlenecks hindering its widespread clinical application and propose promising research avenues. We begin by analyzing stringent demands necessary to truly benefit patients, addressing significant challenges in biomechanics, nanomedicine, and flexible electronics. Subsequently, we delve into skin anatomy, enhancement strategies, nano-carriers, and their underlining mechanisms, highlighting the importance and framework of quantitative modeling. Based on these discussions, we highlight the core strength of TDD, such as automatic precise administration based on feedback and high delivery efficiencies, especially applicable to localized conditions (e.g., central nervous system diseases, tumors). Finally, we envision the future of intelligent TDD device and its operation scenario, aiming to steer research efforts toward faster translation of laboratory innovations into widely used products for sufferers. [ABSTRACT FROM AUTHOR]

More than 20% of pregnant women experience serious complications during pregnancy, that gravely affect the safety of both the mother and the child. Due to the unique state of pregnancy, medication during pregnancy is subject to various restrictions. Nanotechnology is an emerging technology that has been the focus of extensive medical research, and great progress has recently been made in developing sensitive diagnostic modalities and efficient medical treatment. Accumulating evidence has shown that nanodrug delivery systems can significantly improve the targeting, reduce the toxicity and improve the bioavailability of drugs. Recently, some actively targeted nanomedicines have been explored in the treatment of pregnancy-related diseases. This article reviews common types of nanocarriers and active targeting ligands in common pregnancy-related diseases and complications such as preeclampsia, preterm birth, fetal growth restriction, and choriocarcinoma. Finally, the challenges and future prospects in the development of these nanomaterials are discussed, with the aim of providing guidance for future research directions. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) exhibit compromised therapeutic efficacy in many patients with advanced cancers, particularly those with liver metastases. Much of this incapability can be ascribed as an irresponsiveness resulting from the "cold" hepatic tumor microenvironment that acts as T cell "traps" for which there currently lack countermeasures. We report a novel nanomedicine that converts the hepatic immune microenvironment to a "hot" phenotype by targeting hepatic macrophage-centric T cell elimination. Using the nanomedicine, composed of KIRA6 (an endothelium reticulum stress inhibitor), α-Tocopherol nanoemulsions, and anti-PD1 antibodies, we found its potency in murine models of orthotopic colorectal tumors and hepatic metastases, restoring immune responses and enhancing anti-tumor effects. A post-treatment scrutiny of the immune microenvironment landscape in the liver reveals repolarization of immunosuppressive hepatic macrophages, upregulation of Th1-like effector CD4+ T cells, and rejuvenation of dendritic cells along with CD8+ T cells. These findings suggest adaptations of liver-centric immune milieu modulation strategies to improve the efficacy of ICIs for a variety of "cold" tumors and their liver metastases. [Display omitted] • Reducing ER stress and oxidative stress improves TME by repolarizing macrophages. • Liver-centric nanoemulsions reverse immunosuppressive TME of hepatic metastases. • Synergistic nanomedicine of KT nanoemulsions and ICIs converts "cold" tumors to "hot". [ABSTRACT FROM AUTHOR]

Despite impressive advances in immune checkpoint blockade therapy, its efficacy as a standalone treatment remains limited. The influence of chemotherapeutic agents on tumor immunotherapy has progressively come to light in recent years, positioning them as promising contenders in the realm of combination therapy options for tumor immunotherapy. Herein, we present the rational design, synthesis, and biological evaluation of the first example of a Co(III) prodrug (Co2) capable of eliciting a localized cytotoxic effect while simultaneously inducing a systemic immune response via type II immunogenic cell death (ICD). To enhance its pharmacological properties, a glutathione-sensitive polymer was synthesized, and Co2 was encapsulated into polymeric nanoparticles (NP-Co2) to improve efficacy. Furthermore, NP-Co2 activates the GRP78/p-PERK/p-eIF2α/CHOP pathway, thereby inducing ICD in cancer cells. This facilitates the transformation of "cold tumors" into "hot tumors" and augments the effectiveness of the PD-1 monoclonal antibody (αPD-1). In essence, this nanomedicine, utilizing Co(III) prodrugs to induce ICD, provides a promising strategy to enhance chemotherapy and αPD-1 antibody-mediated cancer immunotherapy. [Display omitted] • Cobalt(III)-cyclam prodrug (Co2) selectively activated by ascorbate. • The Co2 induces endoplasmic reticulum stress through activation of the GRP78/p-PERK/p-eIF2α/CHOP pathway, leading to type II immunogenic cell death. • The nanomedicine, utilizing Co2 to induce immunogenic cell death, provides a promising strategy to enhance chemotherapy and αPD-1 antibody-mediated cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Curcumin potentiates the stabilization of atherosclerotic plaques by polarizing macrophages, but its non-specific targeting hinders its clinical application. We aim to harness multifunctional lipid nanoparticles (MLNPs) to facilitate the imaging and targeted delivery of curcumin specifically to inflammatory macrophages, counteracting vulnerable plaques and mitigating the risk of ischemic events. Cholesteryl-9-carboxynonanoate-(125I‑iron oxide nanoparticle/Curcumin)-lipid-coated nanoparticles [9-CCN-(125I-ION/Cur)-LNPs], namely MLNPs, are designed to carry hybrid imaging agents. These agents combine 125I-ION with lipids containing phagocytic 'eat-me' signals, inducing macrophages to engulf the MLNPs. Our research demonstrates that the designed MLNPs accurately accumulate at unstable plaques and are precisely visualized and highlighted by both SPECT and MRI. Furthermore, MLNPs achieve high efficiency in delivering 125I-ION and curcumin to macrophages, ultimately leading to significant M1-to-M2 macrophage polarization. These real-time imaging and polarization capabilities of plaques have immediate clinical applicability and may pave the way for novel therapies to stabilize unstable atherosclerotic plaques. [Display omitted] [ABSTRACT FROM AUTHOR]

Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co -loaded with TLR agonists Poly I:C and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses. [Display omitted] [ABSTRACT FROM AUTHOR]

Sonography with its non-invasive and deep tissue-penetrating characteristics, not only contributes to promising developments in clinical disease diagnosis but also obtains acknowledgments as a prospective therapeutic approach in the field of tumor treatment. However, it remains a challenge for sonography simultaneously to achieve efficient imaging and therapeutic functionality. Here, we present an innovative integrated diagnosis and treatment paradigm by developing the nanomedicine of percarbamide-bromide-mesoporous organosilica spheres (MOS) with RGD peptide modification (PBMR) by loading percarbamide and bromide in MOS which were prepared by a one-step O/W microemulsion method. The PBMR nanomedicine effectively modifies the tumor acoustic environment to improve sonoimaging efficacy and induces sonochemical reactions to enhance the production of reactive oxygen species (ROS) for tumor treatment efficiency under sonography. The combination of PBMR nanomedicine and SDT achieved multiple ROS generation through the controlled sonochemical reactions and significantly boosted the potency of sonodynamic therapy and induced significant tumor regression with non-invasive tissue penetrability and minimizing damage to healthy tissues. Simultaneously, the generation of oxygen gas in the sonochemical process augments ultrasound reflection, resulting in a 4.9-fold increase in imaging grayscale. Our research establishes an effective platform for the synergistic integration of sonoimaging and sonodynamic antitumor therapy, offering a novel approach for precise antitumor treatment in the potential clinical applications. [ABSTRACT FROM AUTHOR]

This article explores the field of nanomedicine and its potential applications in targeted drug delivery. It discusses the concept of "nanocarriers" that can transport drugs to specific organs and infected tissues, minimizing side effects. The article presents two experimental series that demonstrate the synthesis and loading of nanoparticles using polymers and various cargos. The experiments investigate the behavior of the nanoparticles in response to changes in pH, showing promising results for targeted drug delivery. The article highlights the educational opportunities and interdisciplinary connections that can be made through the teaching of nanomedicine in chemistry, biology, and physics classes. [Extracted from the article]

This study provides a detailed investigation into the chemical grafting of multiwalled carbon nanotubes (MWNTs) with starch at various concentrations and reaction temperatures. Utilizing Raman spectroscopy and Fourier-transform infrared spectroscopy (FTIR), we identified structural defects in the MWNTs and characterized the functional groups introduced by the grafting process. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) deepened our understanding of the interactions between starch and MWNTs, and quantified the polysaccharide content. Transmission electron microscopy (TEM) unveiled nanostructures arising from the interplay between MWNTs and starch molecules. Our findings highlight the potential of starch-grafted MWNTs for applications in nanotechnology and nanomedicine, positioning them as a promising material for targeted drug delivery and tissue engineering, aligning with Nano LIFE’s multidisciplinary goals in life sciences, nanosciences and nanomedicine. [ABSTRACT FROM AUTHOR]

Many notable applications have been described for magnetic nanoparticles in delivery of diverse drugs and bioactive compounds into cells, magnetofection for the treatment of cancer, photodynamic therapy, photothermal therapy, and magnetic particle imaging (MPI). In response to the growing demand for magnetic nanoparticles for drug delivery or biomedical imaging applications, more effective and eco-friendly methodologies are required for large-scale biosynthesis of this nanoparticles. The major challenge in the large-scale biomedical application of magnetic nanoparticles lies in its low efficiency and optimization of nanoparticle production can address this issue. In the current study, a prediction model is suggested by the fractional factorial designs. The present study aims to optimize culture media components for improved growth and iron uptake of this strain. The result of optimization for iron uptake by the strain ASFS1 is to increase the production of magnetic nanoparticles by this strain for biomedical applications in the future. In the present study, design of experiment method was used to probe the effects of some key medium components (yeast extract, tryptone, FeSO4, Na2-EDTA, and FeCl3) on Fe content in biomass and dried biomass of strain ASFS1. A 25−1 fractional factorial design showed that Na2-EDTA, FeCl3, yeast extract-tryptone interaction, and FeSO4-Na2-EDTA interaction were the most parameters on Fe content in biomass within the experimented levels (p < 0.05), while yeast extract, FeCl3, and yeast extract-tryptone interaction were the most significant factors within the experimented levels (p < 0.05) to effect on dried biomass of strain ASFS1. The optimum culture media components for the magnetic nanoparticles production by strain ASFS1 was reported to be 7.95 g L−1 of yeast extract, 5 g L−1 of tryptone, 75 μg mL−1 of FeSO4, 192.3 μg mL−1 of Na2-EDTA and 150 μg mL−1 of FeCl3 which was theoretically able to produce Fe content in biomass (158 μg mL−1) and dried biomass (2.59 mg mL−1) based on the obtained for medium optimization. Using these culture media components an experimental maximum Fe content in biomass (139 ± 13 μg mL−1) and dried biomass (2.2 ± 0.2 mg mL−1) was obtained, confirming the efficiency of the used method. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovium and progressive joint destruction which significantly affects both quality of life and socioeconomic status. Admittedly, various treatments are available, but they are usually accompanied by various side effects, from mild to severe, and potentially with adverse events. Tumour necrosis factor‐alpha (TNF‐α) plays a crucial role in the pathophysiology of RA. It promotes inflammatory, apoptosis and necroptosis via TNF receptor‐1 (TNFR1) but elicit anti‐inflammatory effects via TNFR2. Herein, targeting TNFR2 has gained attention in RA studies. Understanding the role of nanomedicine in modulating TNFR2 signalling may be the instrument in development of RA therapies. Nanotechnology has made a significant progress in treating various conditions of diseases since its inception. Due to this, nanomedicine has emerged as a promising therapeutics approach for RA. Recent studies have demonstrated the potential of nanomedicine in RA theranostics, combining therapy and diagnostics for improved treatment outcomes. Owing to the challenges and advancements in the field of nanotechnology, nanoparticles are seen as an applicable candidate in the treatment of RA. In this review, we provide an overview of the role of nanomedicine in targeting TNFR2 for the treatment of RA and highlight the limitations of current therapies as well as the potential of nanocarriers with controlled drug release and active targeting abilities. [ABSTRACT FROM AUTHOR]

Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti‐vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next‐generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally. [ABSTRACT FROM AUTHOR]

In the tumor treatment by Fenton reaction‒based nanocatalytic medicines, the gradual consumption of Fe(II) ions greatly reduces the production of hydroxyl radicals, one of the most active reactive oxygen species (ROS), leading to much deteriorated therapeutic efficacy. Meanwhile, the ROS consumption caused by the highly expressed reduced glutathione (GSH) in the tumor microenvironment further prevents tumor apoptosis. Therefore, using the highly expressed GSH in tumor tissue to promote the Fe(III) reduction to Fe(II) can not only weaken the resistance of tumor to ROS attack, but also generate enough Fe(II) to accelerate the Fenton reaction. In view of this, an allicin‒modified FeO1‐xOH nanocatalyst possessing varied valence states (II, III) has been designed and synthesized. The coexistence of Fe(II)/Fe(III) enables the simultaneous occurrence of Fenton reaction and GSH oxidation, and the Fe(III) reduction by GSH oxidation results in the promoted cyclic conversion of Fe ions in tumor and positive catalytic therapeutic effects. Moreover, allicin capable of regulating cell cycle and suppressing tumor growth is loaded on FeO1‐xOH nanosheets to activate immune response against tumors and inhibit tumor recurrence, finally achieving the tumor regression efficiently and sustainably. This therapeutic strategy provides an innovative approach to formulate efficient antitumor nanomedicine for enhanced tumor treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT In recent years, nanotechnology has revolutionized various sectors, particularly in nanomedicine, where nanomaterials are used for diagnosis, monitoring, control, prevention, and treatment. Among these, silver nanoparticles (AgNPs) stand out due to their remarkable antimicrobial and cytotoxic properties. Traditional chemical synthesis of AgNPs poses significant environmental and health risks. This study introduces a novel, eco‐friendly synthesis method using royal jelly (RJ), a nutrient‐rich secretion from honeybees, to produce AgNPs with potent anticancer effects. Our research provides a detailed investigation into RJ‐mediated AgNPs’ modulation of the VEGFa/PI3K/Akt/MMP‐2 pathway in HeLa and A549 cancer cell lines. AgNP characterization was performed by applying UV–Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) in combination with selected area electron diffraction (SAED). Cell signaling system components were determined by ELISA analysis. The cells were subjected to staining with hematoxylin and eosin to visualize the treatment’s effects. This study focuses on the green synthesis of AgNPs using RJ and its bioactivity against cancer cells. It provides a detailed characterization of the nanoparticles and examines their effects on cancer cells, specifically HeLa cervical cancer and A549 lung cancer cell lines. Green synthesized AgNPs demonstrate significant cytotoxic effects against HeLa and A549 cancer cell lines. The underlying molecular mechanisms contributing to their anticancer activity were elucidated. Our findings revealed a significant decrease in arginase activity upon exposure to AgNPs, accompanied by reductions in PI3K and phosphorylated and total Akt levels, indicative of pathway inhibition. Additionally, RJAgNP demonstrated a capacity to reduce nitric oxide levels and suppress angiogenesis‐related factors like VEGF and MMP‐2 and inflammation‐related factors like TNF‐α and COX‐2, thus impeding angiogenesis and metastasis. Moreover, our results shed light on the involvement of reactive oxygen intermediates (ROIs) in mediating apoptotic pathways, as evidenced by the increase in malondialdehyde (MDA) concentration and the corresponding decrease in Akt levels, ultimately promoting death in cancer cells. Our study contributes significantly to the field of nanomedicine and cancer therapy by introducing the use of green synthesis AgNPs using RJ and providing in‐depth insights into their molecular mechanisms of anticancer action. Our research findings demonstrate the anticancer potential of RJ‐AgNPs by targeting the VEGFa/PI3K/Akt/MMP‐2 pathway and modulation of ROS/RNS in cancer cells. [ABSTRACT FROM AUTHOR]

Background: Prostate Cancer (PCa) is the second most diagnosed urological cancer among men worldwide. Conventional methods used for diagnosis of PCa have several pitfalls which include lack of sensitivity and specificity. On the other hand, traditional treatment of PCa poses challenges such as long-term side effects and the development of multidrug resistance (MDR). Main body: Hence, there is a need for novel PCa agents with the potential to lessen the burden of these adverse effects on patients. Nanotechnology has emerged as a promising approach to support both early diagnosis and effective treatment of tumours by ensuring precise delivery of the drug to the targeted site of the disease. Most cancer-related biological processes occur on the nanoscale hence application of nanotechnology has been greatly appreciated and implemented in the management and therapeutics of cancer. Nuclear medicine plays a significant role in the non-invasive diagnosis and treatment of PCa using appropriate radiopharmaceuticals. This review aims to explore the different radiolabelled nanomaterials to enhance the specific delivery of imaging and therapeutic agents to cancer cells. Thereafter, the review appraises the advantages and disadvantages of these modalities and then discusses and outlines the benefits of radiolabelled nanomaterials in targeting cancerous prostatic tumours. Moreover, the nanoradiotheranostic approaches currently developed for PCa are discussed and finally the prospects of combining radiopharmaceuticals with nanotechnology in improving PCa outcomes will be highlighted. Conclusion: Nanomaterials have great potential, but safety and biocompatibility issues remain. Notwithstanding, the combination of nanomaterials with radiotherapeutics may improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Stem cell therapy is being explored as a potential treatment for idiopathic pulmonary fibrosis (IPF), but its effectiveness is hindered by factors like reactive oxygen species (ROS) and inflammation in fibrotic lungs. Moreover, the distribution, migration, and survival of transplanted stem cells are still unclear, impeding the clinical advancement of stem cell therapy. To tackle these challenges, we fabricate AuPtCoPS trimetallic-based nanocarriers (TBNCs), with enzyme-like activity and plasmid loading capabilities, aiming to efficiently eradicate ROS, facilitate delivery of therapeutic genes, and ultimately improve the therapeutic efficacy. TBNCs also function as a computed tomography contrast agent for tracking mesenchymal stem cells (MSCs) during therapy. Accordingly, we enhanced the antioxidant stress and anti-inflammatory capabilities of engineered MSCs and successfully visualized their biological behavior in IPF mice in vivo. Overall, this study provides an efficient and forward-looking treatment approach for IPF and establishes a framework for a stem cell-based therapeutic system aimed at addressing lung disease. [ABSTRACT FROM AUTHOR]

Advancement in nanotechnology paves new way in nanomedicine via synthesis of various scaffolds bearing multifunctionalities having characteristics of both as diagnostic and therapeutic applications. Quantum dots (QDs) with exceptional luminescent properties exhibited some unbeatable characteristics of small size with ease in surface modifications and thus make them suitable candidates to be used in drug delivery and diagnosis of diseases. Meanwhile, various type of peptides are known in literature for their excellent therapeutic properties and thus make them promising candidates to be used as conjugate partner with the QDs. Highly luminescent properties and surface modifications flexibility of QDs, further urge to use them as promising conjugate partner with many small molecules including peptides and thus found applications in the field of nanomedicines. Thus Peptides ‐QDs conjugates exhibited the properties of both QDs and bioactivity, biocompatibility features of peptides and hence leave behind the limitation of both the individual partners (i. e. QDs and peptides). Thus the combined Peptides‐QDs conjugates acts as theranostic agent for various diseases where these acts as both imaging and drug delivery agent. Hence the present review focused on the theranostic applications of the Peptides‐QDs conjugates in various area of the nanomedicines. Also we focus on the area of improvement and advancement in nanomedicines for the diagnosis and treatment of the diseases in the early stages. [ABSTRACT FROM AUTHOR]

Background: The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. Results: In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. Conclusion: Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future. [ABSTRACT FROM AUTHOR]

Ischemic stroke poses significant challenges in terms of mortality and disability rates globally. A key obstacle to the successful treatment of ischemic stroke lies in the limited efficacy of administering therapeutic agents. Leveraging the unique properties of nanoparticles for brain targeting and crossing the blood–brain barrier, researchers have engineered diverse nanoparticle-based drug delivery systems to improve the therapeutic outcomes of ischemic stroke. This review provides a concise overview of the pathophysiological mechanisms implicated in ischemic stroke, encompassing oxidative stress, glutamate excitotoxicity, neuroinflammation, and cell death, to elucidate potential targets for nanoparticle-based drug delivery systems. Furthermore, the review outlines the classification of nanoparticle-based drug delivery systems according to these distinct physiological processes. This categorization aids in identifying the attributes and commonalities of nanoparticles that target specific pathophysiological pathways in ischemic stroke, thereby facilitating the advancement of nanomedicine development. The review discusses the potential benefits and existing challenges associated with employing nanoparticles in the treatment of ischemic stroke, offering new perspectives on designing efficacious nanoparticles to enhance ischemic stroke treatment outcomes. [ABSTRACT FROM AUTHOR]

AbstractAim(s)MethodsResultsConclusionThis article explores the application of mesalazine-loaded nanoparticles (MLZ-NPs) encapsulated in Abelmoschus esculentus plant polysaccharide-based pellets (MLZ-NPs-Pellets) for ulcerative colitis.MLZ-NPs were prepared and evaluated for diameter, PDI, and entrapment efficiency. In-vitro efficacy study was conducted on Caco-2 cells. MLZ-NPs were encapsulated in polysaccharides to form MLZ-NPs-Pellets and characterised for efficacy in animals and targeting efficiency in human volunteers.Optimised batch of MLZ-NPs were characterised for diameter, PDI, zeta potential and entrapment efficiency which was found to be 145.42 ± 6.75 nm, 0.214 ± 0.049, −31.63 mV and 77.65 ± 2.33(%w/w) respectively. ROS, superoxide and NF-kβ were well controlled in Caco-2 cells when treated with MLZ-NPs. In-vivo data revealed that some parameters (body weight, colon length, lipid peroxidase, and glutathione) recovered significantly in the DSS-induced mice model treated with oral MLZ-NPs-Pellets. Gamma scintigraphy revealed that the formulation can effectively target the colon within 600 min.MLZ-NPs-Pellets can be effectively used for microbial-triggered colon targeting approach in treating ulcerative colitis. [ABSTRACT FROM AUTHOR]

Stem cell therapy is being explored as a potential treatment for idiopathic pulmonary fibrosis (IPF), but its effectiveness is hindered by factors like reactive oxygen species (ROS) and inflammation in fibrotic lungs. Moreover, the distribution, migration, and survival of transplanted stem cells are still unclear, impeding the clinical advancement of stem cell therapy. To tackle these challenges, we fabricate AuPtCoPS trimetallic-based nanocarriers (TBNCs), with enzyme-like activity and plasmid loading capabilities, aiming to efficiently eradicate ROS, facilitate delivery of therapeutic genes, and ultimately improve the therapeutic efficacy. TBNCs also function as a computed tomography contrast agent for tracking mesenchymal stem cells (MSCs) during therapy. Accordingly, we enhanced the antioxidant stress and anti-inflammatory capabilities of engineered MSCs and successfully visualized their biological behavior in IPF mice in vivo. Overall, this study provides an efficient and forward-looking treatment approach for IPF and establishes a framework for a stem cell-based therapeutic system aimed at addressing lung disease. [ABSTRACT FROM AUTHOR]

The review summarises the prospects in the application of graphene and graphene-based nanomaterials (GBNs) in nanomedicine, including drug delivery, photothermal and photodynamic therapy, and theranostics in cancer treatment. The application of GBNs in various areas of science and medicine is due to the unique properties of graphene allowing the development of novel ground-breaking biomedical applications. The review describes current approaches to the production of new targeting graphene-based biomedical agents for the chemotherapy, photothermal therapy, and photodynamic therapy of tumors. Analysis of publications and FDA databases showed that despite numerous clinical studies of graphene-based materials conducted worldwide, there is a lack of information on the clinical trials on the use of graphene-based conjugates for the targeted drug delivery and diagnostics. The review will be helpful for researchers working in development of carbon nanostructures, material science, medicinal chemistry, and nanobiomedicine. [ABSTRACT FROM AUTHOR]

Cancer is a complex disease that affects millions of people and remains a major public health problem worldwide. Conventional cancer treatments, including surgery, chemotherapy, immunotherapy, and radiotherapy, have limited achievements and multiple drawbacks, among which are healthy tissue damage and multidrug-resistant phenotype onset. Increasing evidence shows that many plants' natural products, as well as their bioactive compounds, have promising anticancer activity and exhibit minimal toxicity compared to conventional anticancer drugs. However, their widespread use in cancer therapy is severely restricted by limitations in terms of their water solubility, absorption, lack of stability, bioavailability, and selective targeting. The use of nanoformulations for plants' natural product transportation and delivery could be helpful in overcoming these limitations, thus enhancing their therapeutic efficacy and providing the basis for improved anticancer treatment strategies. The present review is aimed at providing an update on some phytocompounds (curcumin, resveratrol, quercetin, and cannabinoids, among others) and their main nanoformulations showing antitumor activities, both in vitro and in vivo, against such different human cancer types as breast and colorectal cancer, lymphomas, malignant melanoma, glioblastoma multiforme, and osteosarcoma. The intracellular pathways underlying phytocompound anticancer activity and the main advantages of nanoformulation employment are also examined. Finally, this review critically analyzes the research gaps and limitations causing the limited success of phytocompounds' and nanoformulations' clinical translation. [ABSTRACT FROM AUTHOR]

Anticancer therapy urgently needs the development of novel strategies. An innovative molecular target is represented by circular RNAs (circRNAs), single-strand RNA molecules with the 5′ and 3′ ends joined, characterized by a high stability. Although circRNA properties and biological functions have only been partially elucidated, their relationship and involvement in the onset and progression of cancer have emerged. Specific targeting of circRNAs may be obtained with antisense oligonucleotides and silencing RNAs. Nanotechnology is at the forefront of research for perfecting their delivery. Continuous efforts have been made to develop novel nanoparticles (NPs) and improve their performance, materials, and properties regarding biocompatibility and targeting capabilities. Applications in various fields, from imaging to gene therapy, have been explored. This review sums up the smart strategies developed to directly target circRNAs with the fruitful application of NPs in this context. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) has traditionally been managed with vitreoretinal surgery. Although there have been several recent innovations in this surgery to make the retinal approach as uninvasive as possible, the outcomes remain unsatisfactory. Significant complications remain and the complexity of the surgical approach is challenging. The focus of this review was to investigate and discuss the effectiveness of nanomedicine, featuring a wide range of drugs and molecules, as a novel potential treatment for PVR. To date, ocular drug delivery remains a significant issue due to the physiological and anatomical barriers, dynamic or static, which prevent the entry of exogenous molecules. We tried to summarize the nanotechnology-based ophthalmic drugs and new nanoparticles currently under research, with the intention of tackling the onset and development of PVR. The purpose of this review was to thoroughly and analytically examine and assess the potential of nano-based techniques as innovative strategies to treat proliferative vitreoretinopathy (PVR). This study aimed to emphasize the breakthroughs in nanomedicine that provide promising therapeutic options to enhance the results of vitreoretinal surgery and halt disease progression, considering the complexity and difficulty of PVR treatment. The future directions of the nanoparticles and nanotherapies applied to PVR highlight the importance of investing in the development of better designs and novel ophthalmic formulations in order to accomplish a mini-invasive ocular approach, replacing the standard-of-care vitreoretinal surgery. [ABSTRACT FROM AUTHOR]

The structural rigidity of thiourea (TU) motifs has made them useful in supramolecular (bio)materials. However, the role of the TU motif in a single system endowing dual noncovalent interactions, i.e., Hydrogen‐bonding (H‐bonding) association and metal‐coordination interaction, to afford nanomedicine is still unexplored. Herein a smart supramolecular polymeric nanomedicine constructed via TU motifs privileged dual noncovalent interactions, toward synergistic chemo/chemodynamic (CT/CDT) cancer therapy is reported. The study first synthesized a six‐arm star‐shaped amphiphilic polymer vehicle containing pendant TU motifs, poly(acylthiourea‐co‐oligo(ethylene glycol) ethyl acrylate)6 (P(TU‐co‐OEGEA)6), followed by addressing both H‐bonding association and metal‐coordination to fabricate supramolecular nanomedicine (e.g., Dox/Cu@P(TU‐co‐OEGEA)6). Structural privilege and functional diversity of TU motifs constitute an outstanding scaffold, not only offering an H‐bonding site to associate doxorubicin (Dox) but also acting as a ligand to coordinate copper (Cu). Thereby, one TU motif can enable dual noncovalent binding modes, triggering multiple curative outcomes. TU/Dox and TU/Cu noncovalent interactions can induce intermolecular configuration, yielding prompted cargo loading and in vivo stability. Moreover, benefiting from pH‐responsive Dox release and Fenton‐like copper redox chemistry, accompanied by Dox‐induced intratumoral H2O2 elevation and prompted •OH generation, synergistic CT/CDT with extraordinary anti‐tumor efficacy is indeed accomplished. This work provides a new paradigm using TU motifs regulated dual supramolecular forces to meet therapeutic goals. [ABSTRACT FROM AUTHOR]

Background: Convenient therapeutic protocols for hepatocellular carcinoma (HCC) are often ineffective due to late diagnosis and high tumor heterogeneity, leading to poor long-term outcomes. However, recently performed studies suggest that using nanostructures in liver cancer treatment may improve therapeutic effects. Inorganic nanoparticles represent a unique material that tend to accumulate in the liver when introduced in-vivo. Typically, this is a major drawback that prevents the therapeutic use of nanoparticles in medicine. However, in HCC tumours, this may be advantageous because nanoparticles may accumulate in the target organ, where the leaky vasculature of HCC causes their accumulation in tumour cells via the EPR effect. On the other hand, recent studies have shown that combining low- and high-LET radiation emitted from the same radionuclide, such as 161Tb, can increase the effectiveness of radionuclide therapy. Therefore, to improve the efficacy of radionuclide therapy for hepatocellular carcinoma, we suggest utilizing radioactive palladium nanoparticles in the form of 109Pd/109mAg in-vivo generator that simultaneously emits β− particles and Auger electrons. Results: Palladium nanoparticles with a size of 5 nm were synthesized using 109Pd produced through neutron irradiation of natural palladium or enriched 108Pd. Unlike the 109Pd-cyclam complex, where the daughter radionuclide diffuses away from the molecules, 109mAg remains within the nanoparticles after the decay of 109Pd. In vitro cell studies using radioactive 109Pd nanoparticles revealed that the nanoparticles accumulated inside cells, reaching around 50% total uptake. The 109Pd-PEG nanoparticles exhibited high cytotoxicity, even at low levels of radioactivity (6.25 MBq/mL), resulting in almost complete cell death at 25 MBq/mL. This cytotoxic effect was significantly greater than that of PdNPs labeled with β− (131I) and Auger electron emitters (125I). The metabolic viability of HCC cells was found to be correlated with cell DNA DSBs. Also, successful radioconjugate anticancer activity was observed in three-dimensional tumor spheroids, resulting in a significant treatment response. Conclusion: The results indicate that nanoparticles labeled with 109Pd can be effectively used for combined β− - Auger electron-targeted radionuclide therapy of HCC. Due to the decay of both components (β− and Auger electrons), the 109Pd/109mAg in-vivo generator presents a unique potential in this field. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier's intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, there are few kinds of drugs to treat kidney diseases, and many systemic drugs have some problems, such as serious side effects, rapid degradation in the body circulation and so on. At present, active targeting of nanoparticles has become a hot spot in the field of drug delivery, and the exploration of the pathological mechanism related to active targeting of nanoparticles is becoming more and more abundant. OBJECTIVE: To summarize the active targeting strategies in common renal diseases. METHODS: The first author and the second author searched CNKI, Wanfang, VIP, and PubMed databases using “nanoparticles, active targeting, target, kidney, kidney disease” as English key words and “nanoparticles, nanoparticles, targeting, active targeting, kidney disease, kidney” as Chinese key words. All relevant articles published before July 2, 2023 were retrieved, screened, concluded, and summarized. Finally, 62 articles were included for the summary. RESULTS AND CONCLUSION: The active targeting effect of nanoparticles has been studied in many common kidney diseases. The mechanism of active targeting is mainly the binding of ligands and receptors, by modifying the ligand on the nanoparticles to specifically target the receptor on the cells in the kidney; in which way active targeting is realized. Under different renal pathological conditions, the pathological changes of specific kidney sites may become the key breakthrough point to achieve active targeting. Although kidney-targeting nanoparticles have shown promise in the treatment of nonneoplastic kidney diseases, but it is still in the experimental phase in animals, and it is still a long way from applying these results to medical work. [ABSTRACT FROM AUTHOR]

With breast cancer emerging as a pressing global health challenge, characterized by escalating incidence rates and geographical disparities, there is a critical need for innovative therapeutic strategies. This comprehensive research navigates the landscape of nanomedicine, specifically focusing on the potential of magnetic nanoparticles (MNPs), with magnetite (Fe3O4) taking center stage. MNPs, encapsulated in biocompatible polymers like silica known as magnetic silica nanoparticles (MSN), are augmented with phosphotungstate (PTA) for enhanced chemodynamic therapy (CDT). PTA is recognized for its dual role as a natural chelator and electron shuttle, expediting electron transfer from ferric (Fe3+) to ferrous (Fe2+) ions within nanoparticles. Additionally, protein-based charge-reversal nanocarriers like silk sericin and gluten are introduced to encapsulate (MSN-PTA) nanoparticles, offering a dynamic facet to drug delivery systems for potential revolutionization of breast cancer therapy. This study successfully formulates and characterizes protein-coated nanocapsules, specifically MSN-PTA-SER, and MSN-PTA-GLU, with optimal physicochemical attributes for drug delivery applications. The careful optimization of sericin and gluten concentrations results in finely tuned nanoparticles, showcasing uniform size, enhanced negative zeta potential, and remarkable stability. Various analyses, from Dynamic Light Scattering (DLS) and scanning electron microscopy (SEM) to transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Thermogravimetric analysis (TGA), provide insights into structural integrity and surface modifications. Vibrating Sample Magnetometer (VSM) analysis underscores superparamagnetic behavior, positioning these nanocapsules as promising candidates for targeted drug delivery. In vitro evaluations demonstrate dose-dependent inhibition of cell viability in MCF-7 and Zr-75–1 breast cancer cells, emphasizing the therapeutic potential of MSN-PTA-SER and MSN-PTA-GLU. The interplay of surface charge and pH-dependent cellular uptake highlights the robust stability and versatility of these nanocarriers in tumor microenvironment, paving the way for advancements in targeted drug delivery and personalized nanomedicine. This comparative analysis explores the suitability of silk sericin and gluten, unraveling a promising avenue for the development of advanced, targeted, and efficient breast cancer treatments. [ABSTRACT FROM AUTHOR]

Over the course of the last 10 years, there has been a significant amount of advancement in the subject of nanotechnology, which has demonstrated a great deal of potential not only in the realm of technological fields but also in the realm of medical research. It is possible to see a broad variety of uses for zinc oxide nanoparticles (ZnO-NPs) in the field of cancer research, which is being conducted using nanotechnology. Despite the fact that scientific knowledge is continually expanding in terms of its comprehension of the molecular foundation of cancer cells, the number of people who are diagnosed with cancer continues to rise. The World Health Organisation (WHO) forecasted that the number of cancer cases will rapidly rise over the following ten years. ZnO-NPs have established themselves as a viable option for the treatment of cancer as a result of their capacity to trigger apoptosis in cancer cells. Due to the fact that ZnO nanoparticles have been shown to have anticancer, antibacterial, anti-diabetic, and anti-inflammatory activities, they have garnered a lot of interest in the field of biomedicine. The purpose of this study is to provide a summary of the recent research that have been conducted on the application of ZnO-NPS in the medical field. [ABSTRACT FROM AUTHOR]

The authors, actively engaged in the development of mesoporous silica‐based solutions, initially for modified drug release, later for the smart administration of conventional chemotherapeutic cytotoxic drugs, present the evolution of the concept of targeted therapy across different disciplines. They also discuss the diverse therapeutic needs and related challenges (adverse drug effects) that have unfolded over the last 30 years. Nanomedicine potentialities, mainly against cancers, that have emerged globally during the intense research activity of the last few decades, are critically discussed. The authors glimpse the growing potential of immune‐based therapeutic solutions, including those assisted by nanotechnology, as well as molecular targeted therapies (MTT) on which they focus. The advantages offered by targeted molecular therapies, despite the limits of monotargeted therapies, suggest the engineering of multi‐targeted therapies. Nanomedicine solutions such as ligand‐specific internalization and pH‐sensitive drug release that they have extensively tested and recently presented in open literature, still remain available instruments. According to the authors, MTT can offer shining perspectives in the near future that will depend on a thorough comprehension of nanostructures synthesis and tumor physiology. This article gives an interdisciplinary point of view tailored for non‐specialist readers imagining possible future scenarios in the field. [ABSTRACT FROM AUTHOR]

Plant‐derived exosomes (PDEs) are extracellular vesicles (EVs) occurring naturally,which have propitious applications in the development of cost‐effective and fruitful cancer therapy with minimum aftereffects and ramifications. Recent advancements in research based on PDEs demonstrate their extraordinary advantages in cancer therapy. The components of PDEs exhibit accomplished cancer prevention activity and having insignificant or negligible toxicity. The conventional methods to deliver drugs to the target have various problems, several of which can be solved by using PDEs for drug delivery. The main constituents of PDEs are proteins, lipids, DNA and RNA. PDEs are believed to revolutionize cancer therapy due to their magnificent attributes, but only a few clinical trials on PDEs are in progress. The mechanisms and regulations by which PDEs execute anticancer properties are yet not completely understood. Hence, research are conducted worldwide to understand the mechanisms of action of cancer antagonist PDEs more comprehensively and perspicuously. Modified PDEs have prospect in evolution of precision medicine which can bring a new dimension in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, necessitating innovative treatment strategies. PROTACs (PROteolysis Targeting Chimeras) represent a promising therapeutic approach by targeting and degrading oncogenic proteins via the ubiquitin‐proteasome pathway. This study explores the potential of using exosomes as delivery vehicles for PROTACs to enhance treatment efficacy. Exosomes, due to their biocompatibility and inherent targeting capabilities, offer a precise method for delivering PROTACs to CRC cells, potentially overcoming challenges associated with traditional therapies such as drug resistance and off‐target effects. By harnessing the advantages of both exosome‐based delivery and PROTAC technology, this approach aims to improve targeted protein degradation and therapeutic outcomes in CRC treatment. Further research is required to optimize exosome engineering, ensure efficient PROTAC loading, and validate the safety and efficacy of this novel therapeutic strategy through preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

Background: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects. Methods: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. Results: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects. Conclusions: This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT) is a highly cytotoxic molecule with excellent antitumor activity against various cancers. However, its clinical application is severely limited by poor water solubility, easy inactivation, and severe toxicity. Structural modifications and nanoformulations represent two crucial avenues for camptothecin's development. However, the potential for further structural modifications is limited, and camptothecin nanoparticles fabricated via physical loading have the drawbacks of low drug loading and leakage. Prodrug‐based CPT nanoformulations have shown unique advantages, including increased drug loading, reduced burst release, improved bioavailability, and minimal toxic side effects. Stimulus‐responsive CPT nano‐prodrugs that respond to various endogenous or exogenous stimuli by introducing various activatable linkers to achieve spatiotemporally responsive drug release at the tumor site. This review comprehensively summarizes the latest research advances in stimulus‐responsive CPT nano‐prodrugs, including preparation strategies, responsive release mechanisms, and their applications in cancer therapy. Special focus is placed on the release mechanisms and characteristics of various stimulus‐responsive CPT nano‐prodrugs and their application in cancer treatment. Furthermore, clinical applications of CPT prodrugs are discussed. Finally, challenges and future research directions for CPT nano‐prodrugs are discussed. This review to be valuable to readers engaged in prodrug research is expected. [ABSTRACT FROM AUTHOR]