Nanoparticle-based Delivery Systems Research Articles

Nanoparticle Carriers: A New Era of Precise CRISPR/Cas9 Gene Editing.

The revolutionary CRISPR/Cas9 gene editing technology holds immense potential for treating genetic diseases and tackling conditions like cancer. However, efficient delivery remains a significant challenge. This is where nanoparticles come into play, emerging as powerful allies in the realm of drug delivery. Nanoparticles can accommodate larger insertion sizes, enabling the incorporation of larger Cas9 enzymes and complex guide RNAs, thus opening up the possibility of editing previously inaccessible genetic regions. Their relatively straightforward and scalable production processes make them cost-effective options for wider applications. Notably, nanoparticles excel in vivo, demonstrating efficient tissue penetration and targeted delivery, which are crucial for maximizing therapeutic impact while minimizing side effects. This review aims to explore the potential of nanoparticle-based delivery systems for CRISPR/Cas9, highlighting their advantages and challenges in gene editing applications. The diverse range of nanoparticles further bolsters their potential. Polymeric nanoparticles, for instance, offer tunable properties for customization and controlled release of the CRISPR cargo. Lipid-based nanoparticles facilitate efficient cellular uptake and endosomal escape, ensuring the CRISPR components reach the target DNA. Even gold nanoparticles, known for their unique biocompatibility and photothermal properties, hold promise in light-activated editing strategies. Non-viral delivery systems, particularly those based on nanoparticles, stand out due to their inherent advantages. Collectively, the evidence paints a promising picture: nanoparticles are not merely passive carriers but active participants in the CRISPR/Cas9 delivery landscape. Their versatility, efficiency, and safety position them as key enablers of a future where gene editing can revolutionize drug development, offering personalized and targeted therapies for a wide range of diseases.

Harnessing bacterial metabolites for enhanced cancer chemotherapy: unveiling unique therapeutic potentials.

Cancer poses a serious threat to health globally, with millions diagnosed every year. According to Global Cancer Statistics 2024, about 20 million new cases were reported in 2022, and 9.7 million people worldwide died of this condition. Advanced therapies include combination of one or more treatment procedures, depending on the type, stage, and particular genetic constitution of the cancer, which may include surgery, radiotherapy, chemotherapy, immunotherapy, hormone therapy, targeted therapy, and stem cell transplant. Also, awareness about lifestyle changes, preventive measures and screening at early stages has reduced the incidence of the disease; still, there is a major failure in controlling the incidence of cancer because of its complex and multifaceted nature. With increasing interest in bacterial metabolites as possible novel and effective treatment options in cancer therapy, their main benefits include not only direct anticancer effects but also the modulation of the immune system and potential for targeted and combination therapies. They can therefore be used in combination with chemotherapy, radiotherapy, or immunotherapy to improve outcomes or reduce side effects. Furthermore, nanoparticle-based delivery systems have the potential to enhance the potency and safety of anticancer drugs by providing improved stability, targeted release, and controlled delivery.

Nanoarchitectonics of Copper Sulfide Nanoplating for Improvement of Computed Tomography Efficacy of Bismuth Oxide Constructs towards Drugless Theranostics

Abstract Triple-negative breast cancer (TNBC) has emerged as one of the dreadful metastatic tumors in women due to complexity, specificity, and high recurrence, resulting in poor therapeutic outcomes and requiring real-time monitoring for improved theranostics. Despite the success as efficient radiosensitizers and computed tomography (CT)-based contrast agents, bismuth (Bi)-based composites suffer from poor colloidal stability, dose-dependent toxicity, and pharmacokinetic shortcomings, leading to poor therapeutic monitoring. In addition, several small molecule-based therapeutics, including nanoparticle-based delivery systems, suffer from several limitations of poor therapeutic delivery and acquired multidrug resistance by cancer cells, depriving the therapeutic needs. To overcome this aspect, this study demonstrates the fabrication of drug-like/drugless nanoarchitectures based on copper sulfide-nanoplated bismuth oxide (Bi2O3@CuS, shortly BC) composites for improved theranostic efficacy against TNBC. These systematically characterized BC nanocomposites exhibited pH-/near-infrared (NIR, 808 nm) light-responsive degradability towards dual modal therapies. Due to the band transition of Cu species, the designed BC composites displayed exceptional photothermal (PTT) conversion efficiency towards localized PTT effects. In addition to pH-/NIR-responsiveness, the internally overexpressed glutathione (GSH)-responsiveness facilitated the release of Cu2+ species for chemodynamic therapy (CDT) effects. To this end, the Bi3+ species in the core could be fully hydrated in the acidic tumor microenvironment (TME), resulting in GSH depletion and reducing CDT-induced reactive oxygen species (ROS) clearance, thereby ablating tumors. The acid-responsive degradability of CuS resulted in the intratumoral enrichment of BC, demonstrating remarkable CT imaging efficacy in vivo. Together, these pH-/NIR-/GSH-responsive biodegradable BC composites could realize the integrated PTT/CDT/CT theranostics against breast carcinoma.

Nanotechnology-based approaches for targeted drug delivery for the treatment of respiratory tract infections

Background: Nanotechnology has emerged as a promising field for the diagnosis, monitoring, and treatment of respiratory tract infections (RTIs). By leveraging the unique properties of nanoscale delivery systems, nanotechnology can significantly enhance the selectivity and efficacy of antimicrobials, thereby reducing off-target effects. Objective: This review explores the development and application of targeted nanosystems in combating viral, bacterial, and fungal RTIs. Nanotechnology-based systems, including biological and non-biological nanoparticles, offer innovative solutions for overcoming antimicrobial resistance, improving drug bioavailability, and minimizing systemic side effects. RTIs are a leading cause of morbidity and mortality globally, particularly affecting vulnerable populations such as children, the elderly, and immunocompromised individuals. Traditional drug delivery methods face numerous challenges, such as rapid clearance, poor tissue penetration, and drug degradation. Nanoparticle-based delivery systems address these issues by enhancing tissue penetration, providing sustained drug release, and enabling targeted delivery to infection sites. These systems include liposomal delivery, polymeric nanoparticles, dendrimers, and metal-based nanoparticles, each offering unique advantages in treating RTIs. Nanotechnology also plays a crucial role in vaccine development by offering new strategies to enhance immune responses and improve antigen delivery. Furthermore, the review discusses the clinical translation and regulatory considerations for nanotechnology-based drug delivery, emphasizing the need for rigorous testing and quality control to ensure safety and efficacy. Conclusion: Nanotechnology offers promising advancements in the treatment, and prevention of RTIs by enhancing drug delivery and efficacy. By addressing challenges such as antimicrobial resistance and poor tissue penetration, nanotechnology-based systems have the potential to significantly improve patient outcomes.

Targeting Tumor Hypoxia with Nanoparticle-Based Therapies: Challenges, Opportunities, and Clinical Implications.

Hypoxia is a crucial factor in tumor biology, affecting various solid tumors to different extents. Its influence spans both early and advanced stages of cancer, altering cellular functions and promoting resistance to therapy. Hypoxia reduces the effectiveness of radiotherapy, chemotherapy, and immunotherapy, making it a target for improving therapeutic outcomes. Despite extensive research, gaps persist, necessitating the exploration of new chemical and pharmacological interventions to modulate hypoxia-related pathways. This review discusses the complex pathways involved in hypoxia and the associated pharmacotherapies, highlighting the limitations of current treatments. It emphasizes the potential of nanoparticle-based platforms for delivering anti-hypoxic agents, particularly oxygen (O2), to the tumor microenvironment. Combining anti-hypoxic drugs with conventional cancer therapies shows promise in enhancing remission rates. The intricate relationship between hypoxia and tumor progression necessitates novel therapeutic strategies. Nanoparticle-based delivery systems can significantly improve cancer treatment efficacy by targeting hypoxia-associated pathways. The synergistic effects of combined therapies underscore the importance of multimodal approaches in overcoming hypoxia-mediated resistance. Continued research and innovation in this area hold great potential for advancing cancer therapy and improving patient outcomes.

PLGA-PEG Nanoparticles Loaded with Cdc42 Inhibitor for Colorectal Cancer Targeted Therapy.

Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV-vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025-0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation.

Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system

BackgroundEnterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and...

Liposomal encapsulated curcumin attenuates lung cancer proliferation, migration, and induces apoptosis

Lung cancer is one of the most diagnosed types of cancer worldwide, accounting to one fifth of cancer-related deaths. The high prevalence of lung cancer (LC) is due to various factors such as environmental pollution or lifestyle factors such as cigarette smoking. Non-small cell lung cancer (NSCLC) is the most diagnosed type of lung cancer. Despite the availability of several lines of treatment for NSCLC, including surgery, chemotherapy, radiotherapy, immunotherapy, and combinations of these, this disease still has very low survival rate, highlighting the urgent need to develop novel therapeutics. Phytoceuticals, or plant-derived bioactives are a promising source of biologically active compounds. Among these, curcumin is particularly relevant due to its wide range of anticancer, antioxidant, and anti-inflammatory activity. However, its poor solubility causes low bioavailability, severely limiting its clinical application. Encapsulation of curcumin in nanoparticle-based delivery systems such as liposomes holds promise to overcome this limitation. In the present study, we demonstrate promising in vitro anticancer affect or curcumin-loaded liposomes (PlexoZome®) on A549 human lung adenocarcinoma cells. The study reveals how liposomal curcumin functionally supresses the proliferation, migration, and colony formation of these cells whilst also drastically reducing the expression of multiple cancer marker proteins. This work provides foundational data for the development of a curcumin-based nano formulation to be used as therapy for NSCLC.

Bioflavonoid Daidzein: Therapeutic Insights, Formulation Advances, and Future Directions.

Bioflavonoids, are a diverse group of phytonutrients that are widely distributed in fruits, vegetables, grains, teas, and certain medicinal herbs. They are characterized by their antioxidant properties and play essential roles in plant biology, such as providing color to fruits and flowers, protecting plants from environmental stresses. Daidzein, a bioflavonoid classified under natural products, is sourced from plants like soybeans and legumes. It exists in forms such as glycosides and aglycones, with equol and trihydroxy isoflavone being key metabolites formed by gut bacteria. Known for its wide-ranging therapeutic potential, daidzein has shown effects on cardiovascular health, cancer, diabetes, skin conditions, osteoporosis, and neurodegenerative disorders. Its mechanisms include interaction with estrogen receptors, antioxidative and anti-inflammatory properties, and modulation of apoptosis and cell cycles. Recent advances in formulation technologies aimed at enhancing daidzein's bioavailability and efficacy are critically evaluated, including nanoparticle-based delivery systems and encapsulation strategies. Researchers have developed advanced formulations like nanoparticles and liposomes to enhance daidzein's solubility, stability, bioavailability, and targeted delivery. Considered a promising nutraceutical, daidzein warrants further exploration into its molecular actions and safety profile to fully realize its clinical potential. This review offers a succinct overview encompassing therapeutic benefits, chemical characteristics, historical uses, toxicology insights, recent advancements in delivery systems, and future directions for daidzein research.

Strategies for developing self-assembled nanoparticle vaccines against SARS-CoV-2 infection.

In the recent history of the SARS-CoV-2 outbreak, vaccines have been a crucial public health tool, playing a significant role in effectively preventing infections. However, improving the efficacy while minimizing side effects remains a major challenge. In recent years, there has been growing interest in nanoparticle-based delivery systems aimed at improving antigen delivery efficiency and immunogenicity. Among these, self-assembled nanoparticles with varying sizes, shapes, and surface properties have garnered considerable attention. This paper reviews the latest advancements in the design and development of SARS-CoV-2 vaccines utilizing self-assembled materials, highlighting their advantages in delivering viral immunogens. In addition, we briefly discuss strategies for designing a broad-spectrum universal vaccine, which provides insights and ideas for dealing with possible future infectious sarbecoviruses.

Metal-Organic Frameworks for Overcoming the Blood-Brain Barrier in the Treatment of Brain Diseases: A Review.

The blood-brain barrier (BBB) plays a vital role in safeguarding the central nervous system by selectively controlling the movement of substances between the bloodstream and the brain, presenting a substantial obstacle for the administration of therapeutic agents to the brain. Recent breakthroughs in nanoparticle-based delivery systems, particularly metal-organic frameworks (MOFs), provide promising solutions for addressing the BBB. MOFs have become valuable tools in delivering medications to the brain with their ability to efficiently load drugs, release them over time, and modify their surface properties. This review focuses on the recent advancements in molecular-based approaches for treating brain disorders, such as glioblastoma multiforme, stroke, Parkinson's disease, and Alzheimer's disease. This paper highlights the significant impact of MOFs in overcoming the shortcomings of conventional brain drug delivery techniques and provides valuable insights for future research in the field of neurotherapeutics.

Teaming up to overcome challenges toward translation of new therapeutics for osteoarthritis.

As a leading global cause of musculoskeletal-related disability, osteoarthritis (OA) represents a public health urgency. Understanding of disease pathogenesis has advanced substantially in the past decade, yet no disease-modifying therapeutics have advanced to the clinic. To address this challenge, the CARE-AP (Cartilage Repair strategies to alleviate Arthritis Pain) collaborative research team was convened to bring together relevant multidisciplinary expertise and perspectives from across the VA research community nationwide. The first CARE-AP Annual Research Symposium took place (virtually) in February 2022 with roughly 90 participants. A number of innovative and therapeutic strategies were discussed, including siRNA approaches coupled with novel nanoparticle-based delivery systems, cellular engineering approaches to develop reparative cells that can probe the joint environment and respond to disease-specific cues, and novel biofabrication techniques to improve tissue engineering and effect "biological joint replacement." In addition, challenges and advances in rehabilitation approaches, imaging outcomes, and clinical studies were presented, which were integrated into a framework of recommendations for running "preclinical trials" to improve successful clinical translation.

Extracellular vesicle surface display enhances the therapeutic efficacy and safety profile of cancer immunotherapy

Immunotherapy has emerged as a mainstay in cancer therapy, yet its efficacy is constrained by the risk of immune-related adverse events. In this study, we present a nanoparticle-based delivery system that enhances the therapeutic efficacy of immunomodulatory ligands while concurrently limiting systemic toxicity. We demonstrate that extracellular vesicles (EVs), lipid bilayer enclosed particles released by cells, can be efficiently engineered via iEDDA-mediated conjugation to display multiple immunomodulatory ligands on their surface. Display of immunomodulatory ligands on the EV surface conferred substantial enhancements in signaling efficacy, particularly for tumor necrosis factor receptor superfamily (TNFRSF) agonists, where EV surface display served as an alternative FcγR-independent approach to induce ligand multimerization and efficient receptor crosslinking. EVs displaying a complementary combination of immunotherapeutic ligands were able to shift the tumor immune milieu towards an anti-tumorigenic phenotype and significantly suppress tumor burden and increase survival in multiple models of metastatic cancer to a greater extent than an equivalent dose of free ligands. In summary, we present an EV-based delivery platform for cancer immunotherapeutic ligands that facilitates superior anti-tumor responses at significantly lower doses with less side-effects than is possible with conventional delivery approaches.

Advancements in Nanoparticle-Based Gene Delivery Systems for Therapeutic Applications: A Comprehensive Review

Advancements in Nanoparticle-Based Gene Delivery Systems for Therapeutic Applications: A Comprehensive Review

Nanocarriers: Exploring the Potential of Oligonucleotide Delivery.

Nanoparticle-based delivery systems have emerged as promising tools in oligonucleotide therapeutics, facilitating precise and targeted delivery to address several disease conditions. The multifaceted landscape of nanoparticle-based oligonucleotide delivery encompasses the fundamental aspects of nanotechnology in delivery systems, various classes of oligonucleotides, and the growing field of ON-based therapeutics. These ON-based therapeutics are utilized to target specific genetic sequences within cells, offering promising avenues for treating various diseases by regulating gene expression or interfering with specific cellular processes. The integration of nanotechnology in delivery systems offers several advantages, given their intricate systems. Being a diverse class of agents, oligonucleotides provide a wide range of potential owed to each class of agents that support therapeutic interventions. Oligonucleotide-based platforms have demonstrated their versatility in molecular targeting and intervention strategies. Moreover, the complexities and delivery challenges in oligonucleotide therapeutics are expected to be overcome by the application of nanotechnology-based platforms.Because nanoparticles can overcome biological barriers and improve bioavailability, stability, and specificity, their role in developing oligonucleotide delivery systems is greatly valued. The innovative solutions facilitated by nanoparticles are efficient strategies to address the arduous barriers. These strategies beat obstacles like enzymatic degradation, cellular uptake, and immune response, which in turn paves the way for enhanced therapeutic efficacy. This review paper intends to explore the various applications of nanoparticle-mediated oligonucleotide delivery in a variety of diseases. It outlines the promising growth of therapies enabled by these systems, extending from cancer to genetic disorders, neurodegenerative diseases, etc. We have underscored the pivotal role of nanoparticle-based delivery systems in uncovering the full potential of oligonucleotide therapeutics, thereby fostering advancements in precision medicine and targeted therapies.

Engineering nanoparticles-enabled tumor-associated macrophages repolarization and phagocytosis restoration for enhanced cancer immunotherapy

Tumor-associated macrophages (TAMs) are pivotal within the immunosuppressive tumor microenvironment (TME), and recently, have attracted intensive attention for cancer treatment. However, concurrently to promote TAMs repolarization and phagocytosis of cancer cells remains challenging. Here, a TAMs-targeted albumin nanoparticles-based delivery system (M@SINPs) was constructed for the co-delivery of photosensitizer IR820 and SHP2 inhibitor SHP099 to potentiate macrophage-mediated cancer immunotherapy. M@SINPs under laser irradiation can generate the intracellular reactive oxygen species (ROS) and facilitate M2-TAMs to an M1 phenotype. Meanwhile, inhibition of SHP2 could block the CD47-SIRPa pathway to restore M1 macrophage phagocytic activity. M@SINPs-mediated TAMs remodeling resulted in the immunostimulatory TME by repolarizing TAMs to an M1 phenotype, restoring its phagocytic function and facilitating intratumoral CTLs infiltration, which significantly inhibited tumor growth. Furthermore, M@SINPs in combination with anti-PD−1 antibody could also improve the treatment outcomes of PD−1 blockade and exert the synergistic anticancer effects. Thus, the macrophage repolarization/phagocytosis restoration combination through M@SINPs holds promise as a strategy to concurrently remodel TAMs in TME for improving the antitumor efficiency of immune checkpoint block and conventional therapy.

Functionalized chitosan-G-poly caprolactone vaccine delivery system fabricated to display antigen–antibody immune complexes of Mycobacterium tuberculosis elicits immune response in Ex-vivo model

BackgroundVaccine development against tuberculosis remains a global health imperative, necessitating robust immunogenicity and safety profiles. Nanoparticle-based delivery systems offer promising avenues to enhance vaccine efficacy while ensuring tolerability. This study explores the utilization of chitosan micelles as a delivery platform for immune complex vaccination against tuberculosis. Leveraging two key antigens of Mycobacterium tuberculosis, namely HspX and Mpt51, known for their relevance in latent tuberculosis and its co-infection with the human immunodeficiency virus, immune complexes were synthesized in vitro using antibodies raised against these antigens. The immune complexes were then conjugated onto chitosan micelles, characterized for their physicochemical properties, and evaluated for their biocompatibility and immunogenicity.ResultsChitosan nanoparticles conjugated with either antigen or its immune complexes were synthesized as micelles and physicochemical characterizations confirm the formation of micelles without altering the polymer composition. These immune complex-conjugated chitosan micelles were found to be safe, exhibiting no significant hemolytic and cytotoxic activity even at a higher concentration of 400 µg/ml. Peripheral blood mononuclear cells upon stimulation with immune complex-conjugated chitosan micelles showed enhanced cellular uptake and one to two-fold increased expression of key immune markers—interferon gamma and CD-86.ConclusionsThese findings underscore the potential of chitosan nanoparticles as a versatile delivery platform for immune complex vaccination against tuberculosis. While limitations exist, such as including only two markers of immune modulation, this study lays a foundation for future investigations into immune complex vaccine potential in animal models. In conclusion, chitosan micelles carrying immune complexes of HspX and Mpt51 tuberculosis antigens exhibit promising immunogenicity, highlighting their potential as a platform for multi-antigenic vaccine components warranting further in vivo studies.

Tumor targeting in situ aggregation of nanoparticle-to-nanoparticle strategy to simultaneously induce ferroptosis and immunogenic cell death using complementary heparin and protamine molecules

Antibody-drug conjugate (ADC)-based tumor-targeting therapies have demonstrated clinical success in selective drug delivery for cancer treatment. However, the effectiveness of these strategies is hindered by the low amount of loaded payload, lack of sustained efficacy, and insufficient therapeutic performance. In this study, we introduce a novel in situ aggregation-based targeting system using two combinable nanoparticles (NP) that leverage the biocompatible and specific interaction between complementary protamine and heparin molecules. To demonstrate it, we developed protamine-based nanoparticles (PPNC NP) containing cytotoxic negatively charged curcumin (NCur), and heparin-based nanoparticles (HDFe NP) encapsulating doxorubicin and Fe3+. The NP-NP treatment successfully formed aggregates at targeted tumor sites. Our findings demonstrate that the initial administration of PPNC NP effectively targets the tumor and the subsequent administration of complementary HDFe NPs results in their significant accumulation in the tumor tissue, directed by the ‘guidance effect’ of PPNC NPs. This sequence of events promotes the formation of in situ aggregates within the tumor tissue, leading to prolonged nanoparticle accumulation, ferroptosis and immunogenic cell death (ICD). In conclusion, our study demonstrates the effectiveness of a biocompatible and in situ aggregating nanoparticle-nanoparticle system as a solution for overcoming the limitations of current nanoparticle-based delivery systems.

Plant-derived Exosomes: Pioneering Breakthroughs in Therapeutics, Targeted Drug Delivery, and Regenerative Medicine.

Small extracellular vesicles called exosomes, which cells release, have drawn a lot of attention recently because of their ability to serve as therapeutic delivery systems for drugs and regenerative medicine applications. The investigation of plant-based exosomes as a cutting-edge platform for drug administration has emerged as an enticing research topic. A summary of the pharmaceutical feasibility of exosomes generated from plants and their uses in drug delivery along with regenerative medicine are the goals of this review study. Plant exosomes can be combined into nanoparticlebased medication delivery systems to increase their stability, targeting, and cargo delivery capabilities. By loading plant exosomes with therapeutic compounds and encapsulating them within nanoparticles, controlled release and targeted distribution to specific cells or tissues may be achieved. In gene therapy, plant exosomes can be modified to carry nucleic acids like plasmid DNA, siRNA, or miRNA. Effective gene delivery and therapeutic gene expression regulation can be accomplished by encasing nucleic acids in exosomes or surface-modifying exosomes to improve their interaction with target cells. In this review, we through the history and features of plant exosomes, examine how they differ from mammalian exosomes, and consider how they may be used for gene therapy, tissue regeneration, and targeted medication delivery. The difficulties and prospects for creating exosomebased plant medicines are also explored.

The Polarization of Tumor-Associated Macrophages as an Effective Therapeutic Strategy: A Comprehensive Analysis

The complex interplay between tumors and their microenvironment presents challenges in cancer therapy, sparking interest in novel immunotherapeutic strategies. Current therapeutic approaches lack consistency and pose significant risks to patients. Tumor-associated macrophages (TAMs) play a pivotal role in tumor progression or inhibition, depending on their polarization state. This comprehensive analysis explores the potential of selectively repolarizing TAMs towards an anti-tumor phenotype as an effective therapeutic strategy. Nanoparticle-based delivery systems, such as polymeric, lipid-based, and inorganic nanoparticles, offer promising TAM targeting and repolarization avenues. These strategies demonstrate the ability to shift TAMs from a pro-tumoral M2 phenotype to an anti-tumoral M1 phenotype, resulting in significant anti-tumor effects. These processes have been both in vivo and in vitro, depending on the progress of the process. Nanoparticles, for example, have primarily been in vitro, but some have reached the in vivo stage. Despite the complexity of tumor immunology, the repolarization of TAMs emerges as a promising and versatile immunotherapeutic approach with reduced adverse effects compared to traditional treatments. This study underscores the importance of continued research and development in TAM repolarization, paving the way for future advancements and improved cancer therapies.