Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin.

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic-organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.

An overview of phospholipid enriched-edge activator-based vesicle nanocarriers: New paradigms to treat skin cancer.

Skin cancer poses a significant global health concern necessitating innovative treatment approaches. This review explores the potential of vesicle nanoformulation incorporating EA (edge activators) to overcome barriers in skin cancer management. The skin's inherent protective mechanisms, specifically the outermost layer called the stratum corneum and the network of blood arteries, impede the permeation of drugs. Phospholipid-enriched EA based nanoformulation offer a promising solution by enhancing drug penetration through skin barriers. EAs like Span 80, Span 20, Tween 20, and sodium cholate etc., enhance vesicles deformability, influencing drug permeation. This review discusses topical application of drugs treat skin cancer, highlighting challenges connected with the conventional liposome and the significance of using EA-based nanoformulation in overcoming these challenges. Furthermore, it provides insights into various EA characteristics, critical insights, clinical trials, and patents. The review also offers a concise overview of composition, preparation techniques, and the application of EA-based nanoformulation such as transfersomes, transliposomes, transethosomes, and transniosomes for delivering drugs to treat skin cancer. Overall, this review intends to accelerate the development of formulations that incorporate EA, which would further improve topical drug delivery and enhance therapeutic outcomes in skin cancer treatment.

Enhanced Tumor-Targeted Delivery of Arginine-Rich Peptides via a Positive Feedback Loop Orchestrated by Piezo1/integrin ß1 Signaling Axis.

Peptide-based drugs hold great potential for cancer treatment, and their effectiveness is driven by mechanisms on how peptides target cancer cells and escape from potential lysosomal entrapment post-endocytosis. Yet, the mechanisms remain elusive, which hinder the design of peptide-based drugs. Here hendeca-arginine peptides (R11) are synthesized for targeted delivery in bladder carcinoma (BC), investigated the targeting efficiency and elucidated the mechanism of peptide-based delivery, with the aim of refining the design and efficacy of peptide-based therapeutics. It is demonstrated that the over-activated Piezo1/integrin ß1 (ITGB1) signaling axis significantly facilitates tumor-targeted delivery of R11 peptides via macropinocytosis. Furthermore, R11 peptides formed hydrogen bonds with integrin ß1, facilitating targeting and penetration into tumor cells. Additionally, R11 peptides protected integrin ß1 from lysosome degradation, promoting its recycling from cytoplasm to membrane. Moreover, this findings establish a positive feedback loop wherein R11 peptides activate Piezo1 by increasing membrane fusion, promoting Ca2+ releasing and resulting in enhanced integrin ß1-mediated endocytosis in both orthotopic models and clinical tissues, demonstrating effective tumor-targeted delivery. Eventually, the Piezo1/integrin ß1 signaling axis promoted cellular uptake and transport of peptides, establishing a positive feedback loop, promoting mechanical delivery to cancer and offering possibilities for drug modification in cancer therapy.

Recent advances in mesoporous silica nanoparticles formulations and drug delivery for wound healing.

Wound healing is a natural process that can be disrupted by disease. Nanotechnology is a promising platform for the development of new therapeutic agents to accelerate acute and chronic wound healing. Drug delivery by means of nanoparticles as well as wound dressings have emerged as suitable options to improving the healing process. The characteristics of mesoporous silica nanoparticles (MSNs) make them efficient carriers of pharmaceutical agents alone or in combination with dressings. In order to maximize the effect of a drug and minimize its adverse consequences, it may be possible to include targeted and intelligent release of the drug into the design of MSNs. Its use to facilitate closure of adjacent sides of a cut as a tissue adhesive, local wound healing, controlled drug release and induction of blood coagulation are possible applications of MSNs. This review summarizes research on MSN applications for wound healing. It includes a general overview, wound healing phases, MSN formulation, therapeutic possibilities of MSNs and MSN-based drug delivery systems for wound healing.

Microencapsule delivery systems of functional substances for precision nutrition.

Microencapsulation, a typical core-shell structure technology, encapsulates functional active ingredients for protection, controlled release, and targeted delivery. In precise nutrition, the focus is on utilizing microcapsule delivery systems for personalized dietary supplements and disease intervention. This chapter outlines the morphological structure of microcapsules, common wall materials, and preparation techniques. It discusses the characteristics of different hydrophilic and lipophilic functional factors and their function as dietary supplements. The role of microencapsulation on the controlled release, odor masking, and enhanced bioavailability of functional factors is explored. Additionally, the application of microcapsule delivery systems in nutritional interventions for diseases like inflammatory bowel disease, alcoholic/fatty liver disease, diabetes, and cancer is introduced in detail. Lastly, the chapter proposes the future developments of anticipation in responsive wall materials for precise nutrition interventions, including both challenges and opportunities.

Advancements in increasing efficiency of hydrogen sulfide in therapeutics: Strategies for targeted delivery as prodrugs.

Hydrogen sulfide (H2S) has emerged as a potent therapeutic agent with diverse physiological functions, including vasodilation, anti-inflammation, and cytoprotection. However, its clinical application is limited due to its volatility and potential toxicity at high concentrations. To address these challenges, researchers have developed various H2S prodrugs that release H2S in a controlled and targeted manner. The review underscores the importance of targeting and delivery strategies in maximizing the therapeutic potential of H2S, a gasotransmitter with diverse physiological functions and therapeutic effects. By summarizing recent advancements, the review provides valuable insights for researchers and clinicians interested in harnessing the therapeutic benefits of H2S while minimizing off-target effects and toxicity. The integration of novel targeting and delivery approaches not only enhances the efficacy of H2S-based therapeutics but also expands the scope of potential applications, offering promising avenues for the development of new treatments for a variety of diseases and disorders.

Vincristine in Cancer Therapy: Mechanisms, Efficacy, and Future Perspectives.

Cancer remains one of the predominant causes of mortality globally, accounting for over 10 million deaths each year. Despite advancements in medical treatments, the challenge of resistance and treatment failure persists, necessitating innovative approaches. Traditional cancer treatments include surgery, chemotherapy, radiation therapy, and pharmaceutical therapy. In recent years, significant attention has been directed towards plant-derived compounds as potential chemotherapeutic agents and preventive measures against cancer. Vincristine, a distinguished alkaloid derived from plant secondary metabolites, has shown considerable efficacy in cancer treatment. As a member of the antimitotic class of compounds, vincristine disrupts the cell cycle by causing aberrations in microtubule function, thereby inhibiting cell division and proliferation. This mechanism of action positions vincristine as a potent agent against various malignancies. Its role in combination therapy is crucial, as it is often administered in low doses alongside other chemotherapeutic agents to enhance its efficacy and reduce the risk of resistance. In the realm of medicinal chemistry, understanding vincristine's molecular mechanism is paramount. Detailed investigations into its interaction with cellular components can provide insights into its antineoplastic properties. This review aimed to elucidate vincristine's mechanism of action and structure-activity relationship, and summarize current in vitro and in vivo studies evaluating its efficacy. Moreover, it discusses innovative strategies, including nanotechnology-based delivery systems, designed to optimize vincristine formulations. These advanced delivery systems aim to improve bioavailability, target specificity, and minimize systemic toxicity. This comprehensive analysis underscores the critical role of vincristine in contemporary cancer treatment and highlights future directions for research and development in this field.

Nanocarrier-Based Delivery Approaches of Mangiferin: An Updated Review on Leveraging Biopharmaceutical Characteristics of the Bioactive.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

Micelle-encapsulated IR783 for enhanced photothermal therapy in mouse breast cancer.

BACKGROUND: Photothermal therapy, an emerging cancer treatment, selectively eliminates lesions using photothermal compounds that convert light into heat. IR783, a near-infrared fluorescent heptamethine cyanine dye, has been used to achieve selective hyperthermic effects in target tissues via near-infrared irradiation. To implement IR783 as a photothermal agent, IR783 biodistribution must be calibrated to achieve a constant and uniform concentration in target cells. Accordingly, we developed micelle-encapsulated IR783 (IR783 micelles) and evaluated their effectiveness as photothermal drugs. METHODS: In vitro, the photothermic effects of free IR783 and IR783 micelle solutions induced by near-infrared light irradiation were analyzed. Additionally, we investigated the mechanism of cell death mediated by photothermal therapy using free IR783 and IR783 micelles in mouse breast cancer (EMT6) cells. In vivo, the efficacy of photothermal therapy with both free IR783 and IR783 micelles was examined in EMT6-bearing mice. RESULTS: In vitro, the temperature of free and micelle-encapsulated IR783 solutions increased after near-infrared irradiation. Near-infrared irradiation with free IR783 and IR783 micelles induced cytotoxicity in cancer cells by generating heat. In vivo, IR783 micelles elicited more preferential tumor tissue uptake and enhanced the antitumor effects of photothermal therapy at a lower light dose relative to free IR783. CONCLUSIONS: Overall, these results suggest that IR783 micelles could accumulate in mouse breast cancer tissues and exhibit enhanced antitumor effects when used as a photothermal therapy, with superior effects obtained at 2.1 W/cm2 (252 J/cm2) compared with that of free IR783.

Adeno-associated virus therapies: Pioneering solutions for human genetic diseases.

Adeno-associated virus (AAV) has emerged as a fundamental component in the gene therapy landscape, widely acknowledged for its effectiveness in therapeutic gene delivery. The success of AAV-based therapies, such as Luxturna and Zolgensma, underscores their potential as a leading vector in gene therapy. This article provides an in-depth review of the development and mechanisms of AAV vector-based therapies, offering a comprehensive analysis of the latest clinical trial outcomes in central nervous system (CNS) diseases, ocular conditions, and hemophilia, where AAV therapies have shown promising results. Additionally, we discusse the selection of administration methods and serotypes tailored to specific diseases. Our objective is to showcase the innovative applications and future potential of AAV-based gene therapy, laying the groundwork for continued clinical advancements.

Advances in targeted delivery of mRNA into immune cells for enhanced cancer therapy.

Messenger RNA (mRNA) therapy has been applied to the treatment of various human diseases including malignant tumors. Increasing evidences have shown that mRNA can enhance the efficacy of cancer immunotherapy by modulating the functions of immune cells and stimulating their activity. However, mRNA is a type of negatively charged biomacromolecules that are susceptible to serum nucleases and cannot readily cross the cell membrane. In the past few decades, various nanoparticles (NPs)-based delivery systems have been rationally designed and developed to facilitate the intracellular uptake and cytosolic delivery of mRNA. More importantly, by means of the specific recognition between the targeting ligands decorated on NP surface and receptors specifically expressed on immune cells, these mRNA delivery systems could be functionalized to target immune cells to further enhance the mRNA-based cancer immunotherapy. In this review, we briefly introduced the advancements of mRNA in cancer therapy, discussed the challenges faced by mRNA delivery, and systematically summarized the recent development in NPs-based mRNA delivery systems targeting various types of immune cells for cancer immunotherapy. The future development of NPs-mediated targeted mRNA delivery and their challenges in clinical translation are also discussed.

Responding to Hitch in Fighting Mycobacterium Tuberculosis Through Arginine Multi Functionalized Mucoadhesive SNEDDS of Rifampicin.

The study aimed to develop thiolated pluronic-based self-emulsifying drug delivery system (SNEDDS) targeted delivery of Rifampicin coated by arginine for enhanced drug loading, mucoadhesion, muco penetration, site-specific delivery, stabilized delivery against intracellular mycobacterium tuberculosis (M. tb), decreased bacterial burden and production by intracellular targeting. Oleic oil, PEG 200 and Tween 80 are selected as oil, co-surfactant and surfactant based on solubilizing capacity and pseudo ternary diagram region. Coating of thiolated polymer on SNEDDS with ligand arginine (Arg-Th-F407 SNEDDDS) decreased bacterial burden and production by intracellular targeting in macrophages. Formulation are evaluated through scanning electron microscope (SEM), EDAX analysis, diffraction laser scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and thermal analysis (DSC & TGA). Hydrodynamic diameter of thiolated polymeric SNEDDS (Th-F407 SNEDDS) and Arg-Th-F407 SNEDDS is observed to be 148.4 and 188.5 nm with low PDI of 0.4 and 0.3, respectively. Invitro drug release study from Arg-Th-F407 SNEDDS indicates 80% sustained release in 72 h under controlled conditions. Arg-Th-F407 SNEDDDS shows excellent capability of killing M.tb strains in macrophages even at low dose as compared to traditional rifampicin (RIF) and is found biocompatible, non-cytotoxic, and hemocompatible. Therefore, Arg-Th-F407 SNEDDDS of RIF proved ideal for targeting and treating M.tb strains within macrophages.

Application of galactosylated albumin for targeted delivery of triptolide to suppress hepatocellular carcinoma progression through inhibiting de novo lipogenesis.

Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-associated death globally with a lack of efficient therapy. The pathogenesis of HCC is a complex and multistep process, highly reliant on de novo lipogenesis, from which tumor cells can incorporate fatty acids to satisfy the necessary energy demands of rapid proliferation and provide survival advantages. Triptolide (TP) is a bioactive ingredient exhibiting potent abilities of anti-proliferation and lipid metabolism regulation, but its clinical application is constrained because of its toxicity and non-specific distribution. The present study has developed galactosylated bovine serum albumin nanoparticles loaded with TP (Gal-BSA-TP NPs) to alleviate systemic toxicity and increase tumor-targeting and antitumor efficacy. Furthermore, Gal-BSA-TP NPs could inhibit de novo lipogenesis via the p53-SREBP1C-FASN pathway to deprive the fuel supply of HCC, offering a specific strategy for HCC treatment. In general, this study provided a biocompatible delivery platform for targeted therapy for HCC from the perspective of de novo lipogenesis.

Design of nanosystems for melanoma treatment.

Melanoma is a prevalent and concerning form of skin cancer affecting millions of individuals worldwide. Unfortunately, traditional treatments can be invasive and painful, prompting the need for alternative therapies with improved efficacy and patient outcomes. Nanosystems offer a promising solution to these obstacles through the rational design of nanoparticles (NPs) which are structured into nanocomposite forms, offering efficient approaches to cancer treatment procedures. A range of NPs consisting of polymeric, metallic and metal oxide, carbon-based, and virus-like NPs have been studied for their potential in treating skin cancer. This review summarizes the latest developments in functional nanosystems aimed at enhancing melanoma treatment. The fundamentals of these nanosystems, including NPs and the creation of various functional nanosystem types, facilitating melanoma treatment are introduced. Then, the advances in the applications of functional nanosystems for melanoma treatment are summarized, outlining both their benefits and the challenges encountered in implementing nanosystem therapies.

Chitosan-chondroitin sulfate-daidzein nanoconjugate ameliorates glucocorticoid induced osteoporosis in vivo.

The use of nanotechnology and polymer-based carriers in osteoporosis treatment offers promising avenues for targeted drug delivery and enhanced therapeutic efficacy. In this study, we developed a novel nanoconjugate composed of Chitosan (CH), Chondroitin Sulfate (CS), and Daidzein (DZ) to treat glucocorticoid-induced osteoporosis in an in vivo zebrafish model. The CH-CS-DZ nanoconjugate were synthesized using the ionic gelation method, with a CH: CS ratio of 1:1 and a 3 % DZ concentration was identified as optimal for further analysis. The resulting nanoparticles exhibited a particle size of 401.2 ± 0.87 nm. The polydispersity index (PDI) and zeta potential of nanoconjugate were of 0.147 ± 0.04 and 43.55 ± 0.68 mV respectively. Drug release studies demonstrated that 79.66 ± 4.04 % of DZ was released under physiological conditions (pH 7.5) after 96 h, indicating a sustained release profile beneficial for prolonged therapeutic effects. In vivo, studies using zebrafish larvae revealed a significant reduction in oxidative stress and apoptosis in the CH-CS-DZ treated group compared to the glucorticoid dexamethasone (Dex) treated group. Specifically, reactive oxygen species (ROS) levels were reduced, and lipid peroxidation was markedly decreased (p < 0.001) in the CH-CS-DZ treated group. Additionally, the survival and hatching rates of CH-CS-DZ-treated larvae were 94 % and 95 %, respectively, significantly higher than those in the Dex-treated group. The CH-CS-DZ nanoconjugate also restored bone mineralization, as evidenced by a significant increase in calcium deposition (p < 0.001) and alkaline phosphatase (ALP) activity (122 ± 0.4 U/L), compared to the Dex group (84 ± 0.7 U/L). Gene expression analysis showed upregulation of OPG and ALP and downregulation of RANKL and RUNX2b, further indicating the anti-osteoporotic potential of the CH-CS-DZ nanoconjugates. These findings suggest that polymer-based nanoconjugates like CH-CS-DZ can effectively mitigate osteoporosis through targeted delivery and sustained release, offering a potent strategy for bone health restoration.

Membrane-coated nanoparticles as a biomimetic targeted delivery system for tumour therapy.

Drug therapy towards tumours often causes adverse effects because of their non-specific nature. Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery. By camouflaging the nanoparticles with natural derived or artificially modified cell membranes, the nano-payloads are bestowed with properties from cell membranes such as longer circulation, tumour or inflammation-targeting, immune stimulation, augmenting the performance of traditional therapeutics. In this review, we review the development of membrane coating technology, and summarise the technical details, physicochemical properties, and research status of membrane-coated nanoparticles from different sources in tumour treatment. Finally, we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use. Taken together, membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.

Nanofiber-Based Drug Delivery Systems: A Review on Its Applications, Challenges, and Envisioning Future Perspectives.

Nanomaterials, especially nanofibers, hold considerable promise as drug delivery systems (DDS) by providing targeted administration of drugs due to their unique properties, such as large surface area, high porosity, and mechanical robustness. Nanofibers can be fabricated using various techniques like electrospinning, self-assembly, phase separation, and template synthesis, offering properties such as adjustable size, shape, high precision, and biodegradability. Additionally, features such as multiple target functionalization, controlled release of the drug, and prolonged circulation of the drug make nanofibers particularly suitable for biomedical applications, including drug delivery, tissue regeneration, and biosensing. This comprehensive review explores the characteristics, types, fabrication methods, and applications of nanofibers. Diverse types of polymer nanofibers are used in drug delivery, such as blended nanofibers, core-shell nanofibers, and layer-by-layer assembly, each demonstrating their own advantages in controlled drug release and targeted therapy. Electrospun nanofibers are extensively utilized in biomedical applications due to their superior mechanical performance and high porosity and advancements in coaxial electrospinning enabling the fabrication of core-shell nanofibers, offering controlled drug release kinetics and protection of loaded molecules. These nanofibers demonstrate enhanced bioactivity and biocompatibility and can find application in tissue engineering. Furthermore, this review addresses the challenges associated with nanofiber production, including reproducibility and scalability. Nanofibers exhibit the potential to revolutionize medical treatment across diverse therapeutic areas. Future research directions and challenges in nanofiber-based drug delivery discussed in this review offer guidance for further advancements in this rapidly evolving field.

Dihydroxyphenylalanine-conjugated high molecular weight polyethylenimine for targeted delivery of Plasmid.

High molecular weight polyethylenimine (HMW PEI; branched 25 kDa PEI) has been widely investigated for gene delivery due to its high transfection efficiency. However, the toxicity and lack of targeting to specific cells have limited its clinical application. In the present investigation, L-3, 4-dihydroxyphenylalanine (L-DOPA) was conjugated on HMW PEI in order to target L-type amino acid transporter 1 (LAT-1) and modulate positive charge density on the surface of polymer/plasmid complexes (polyplexes). The results of biophysical characterization revealed that the PEI conjugates are able to form nanoparticles ≤ 180 nm with the zeta potential ranging from + 9.5-12.4 mV. These polyplexes could condense plasmid DNA and protect it against nuclease digestion at the carrier to plasmid ratios higher than 4. L-DOPA conjugated PEI derivatives were complexed with a plasmid encoding human interleukin-12 (hIL-12). Targeted polyplexes showed up to 2.5 fold higher transfection efficiency in 4T1 murine mammary cancer cell line, which expresses LAT-1, than 25 kDa PEI polyplexes prepared in the same manner. The cytotoxicity of these polyplexes was also substantially lower than the unmodified parent HMW PEI. These results support the use of L-3, 4-dihydroxyphenylalanine derivatives of PEI in any attempt to develop a LAT-1 targeted gene carrier.

Targeted Nano-Based Systems for the Anti-Obesity Agent's Delivery.

Obesity is a global health concern and a chronic disease that is accompanied by excessive fat storage in adipose and nonadipose tissues. An increase in the body-mass index (BMI) is directly proportional to the 2- to 3.9-fold increase in all-cause mortality in obesity. If left untreated for a longer period, obesity-related metabolic, cardiovascular, inflammatory, and malignant diseases reduce life expectancy. Currently, most of the anti-obesity drugs have failed and fallen into disrepute, either due to their ineffectiveness or adverse effects. In this review, depending on their enhanced pharmacokinetic and biodistribution profiles, whether nanocarriers alter the basic properties and bioactivity of anti-obesity drugs used in clinical practice are debated. First, nanocarriers can improve the safety of still-used anti-obesity drugs by lowering their systemic toxicity through increasing targeting efficacy and preventing drug carrier toxicity. Second, when the micro-ribonucleic acids (miRNAs), which are aberrantly expressed in obesity and obesity-related diseases, are encapsulated into nanoparticles, they are effective in multiple obesity-related metabolic pathways and gene networks. Finally, a synergistic anti-obesity effect with low dose and low toxicity can be obtained with the combinatory therapy applied by encapsulating the anti-obesity drug and gene in the same nanocarrier delivery vehicle.

Synergistic Photothermal Therapy and Chemotherapy Enabled by Tumor Microenvironment-Responsive Targeted SWCNT Delivery.

As a novel therapeutic approach, photothermal therapy (PTT) combined with chemotherapy can synergistically produce antitumor effects. Herein, dithiodipropionic acid (DTDP) was used as a donor of disulfide bonds sensitive to the tumor microenvironment for establishing chemical bonding between the photosensitizer indocyanine green amino (ICG-NH2) and acidified single-walled carbon nanotubes (CNTs). The CNT surface was then coated with conjugates (HD) formed by the targeted modifier hyaluronic acid (HA) and 1,2-tetragacylphosphatidyl ethanolamine (DMPE). After doxorubicin hydrochloride (DOX), used as the model drug, was loaded by CNT carriers, functional nano-delivery systems (HD/CNTs-SS-ICG@DOX) were developed. Nanosystems can effectively induce tumor cell (MCF-7) death in vitro by accelerating cell apoptosis, affecting cell cycle distribution and reactive oxygen species (ROS) production. The in vivo antitumor activity results in tumor-bearing model mice, further verifying that HD/CNTs-SS-ICG@DOX inhibited tumor growth most significantly by mediating a synergistic effect between chemotherapy and PTT, while various functional nanosystems have shown good biological tissue safety. In conclusion, the composite CNT delivery systems developed in this study possess the features of high biocompatibility, targeted delivery, and responsive drug release, and can achieve the efficient coordination of chemotherapy and PTT, with broad application prospects in cancer treatment.