Targeted Drug Delivery Systems Research Articles

NANOTECHNOLOGY IN U.S. MEDICAL DIAGNOSTICS: A COMPREHENSIVE REVIEW

This comprehensive review evaluates the advancements, potential, and ethical implications of nanotechnology in medical diagnostics within the U.S. healthcare system. The primary objective was to assess how nano-tools are revolutionizing early disease detection and management. The methodology involved a systematic review of peer-reviewed literature, focusing on studies published between 2000 and 2023. Data sources included academic databases such as PubMed, Scopus, and Web of Science, supplemented by secondary sources like journals and conference proceedings. The study emphasized the historical development of nanotechnology in diagnostics, current innovations, and future prospects in the field. Key findings reveal significant advancements in nano-diagnostic tools, highlighting their increased sensitivity and specificity in early disease detection. Innovations such as nano-enabled imaging and targeted drug delivery systems have shown potential in personalizing patient care. However, the study also identified challenges, including ethical concerns related to patient privacy, data security, and the need for comprehensive regulatory frameworks. The review concludes that while nanotechnology in diagnostics offers transformative potential, it also presents unique challenges. Recommendations for industry leaders and policymakers include fostering innovation within ethical and safety boundaries, investing in research, and establishing clear regulatory guidelines. Future research directions emphasize long-term efficacy and safety studies, cost-effective manufacturing processes, and exploring new applications in disease management. This study underscores the pivotal role of nanotechnology in shaping the future of healthcare diagnostics.

Internet of Bio Nano Things-based FRET nanocommunications for eHealth.

The integration of the Internet of Bio Nano Things (IoBNT) with artificial intelligence (AI) and molecular communications technology is now required to achieve eHealth, specifically in the targeted drug delivery system (TDDS). In this work, we investigate an analytical framework for IoBNT with Forster resonance energy transfer (FRET) nanocommunication to enable intelligent bio nano thing (BNT) machine to accurately deliver therapeutic drug to the diseased cells. The FRET nanocommunication is accomplished by using the well-known pair of fluorescent proteins, EYFP and ECFP. Furthermore, the proposed IoBNT monitors drug transmission by using the quenching process in order to reduce side effects in healthy cells. We investigate the IoBNT framework by driving diffusional rate models in the presence of a quenching process. We evaluate the performance of the proposed framework in terms of the energy transfer efficiency, diffusion-controlled rate and drug loss rate. According to the simulation results, the proposed IoBNT with the intelligent bio nano thing for monitoring the quenching process can significantly achieve high energy transfer efficiency and low drug delivery loss rate, i.e., accurately delivering the desired therapeutic drugs to the diseased cell.

Probe the nanoparticle-nucleus interaction via coarse-grained molecular model.

The present study reports on a computational model that systematically evaluates the effect of physical factors, including size, surface modification, and rigidity, on the nuclear uptake of nanoparticles (NPs). The NP-nucleus interaction is a crucial factor in biomedical applications such as drug delivery and cellular imaging. While experimental studies have provided evidence for the influence of size, shape, and surface modification on nuclear uptake, theoretical investigations on how these physical factors affect the entrance of NPs through the nuclear pore are lacking. Our results demonstrate that larger NPs require a higher amount of energy to enter the nucleus compared to smaller NPs. This highlights the importance of size as a critical factor in NP design for nuclear uptake. Additionally, surface modification of NPs can impact the nuclear uptake pathway, indicating the potential for tailored NP design for specific applications. Notably, our findings also reveal that the rigidity of NPs has a significant effect on the transport process. The interplay between physicochemical properties and nuclear pore is found to determine nuclear uptake efficiency. Taken together, our study provides new insights into the design of NPs for precise and controllable NP-nucleus interaction, with potential implications for the development of efficient and targeted drug delivery systems and imaging agents.

Evaluating methods to create protein functionalized catanionic vesicles.

Catanionic surfactant vesicles (SVs) composed of sodium dodecylbenzenesulfonate (SDBS) and cetyltrimethylammonium tosylate (CTAT) have potential applications as targeted drug delivery systems, vaccine platforms, and diagnostic tools. To facilitate these applications, we evaluated various methods to attach proteins to the surface of SDBS/CTAT vesicles. Acid phosphatase from wheat germ was used as a model protein. Acid phosphatase was successfully conjugated to vesicles enriched with a Triton-X 100 derivative containing an unsaturated ester. Enzymatic activity of acid phosphatase attached to vesicles was assessed using an acid phosphatase assay. Results from the acid phosphatase assay indicated that 15 ± 3% of the attached protein remained functional but the presence of vesicles interferes with the assay. DLS and zeta potential results correlated with the protein functionalization studies. Acid phosphatase functionalized vesicles had an average diameter of 175 ± 85 nm and an average zeta potential of -61 ± 5 mV in PBS. As a control, vesicles enriched with Triton-X 100 were prepared and analyzed by DLS and zeta potential measurements. Triton X-100 enriched vesicles had an average diameter of 140 ± 67 nm and an average zeta potential of -49 ± 2 mV in PBS. Functionalizing the surface of SVs with proteins may be a key step in developing vesicle-based technologies. For drug delivery, antibodies could be used as targeting molecules; for vaccine formulation, functionalizing the surface with spike proteins may produce novel vaccine platforms.

Advances of Niosomes as a Targeted Drug Delivery Syste

Due to a lack of effective treatment factor or drug delivery systems many diseases go untreated especially when side effects and toxicities are the main cause of concern. Consequently we chose novel drug delivery system. The structure of niosomes is made up of three moieties hydrophilic amphiphilic and lipophilic which can accommodate several drug molecules with a wide range of solubilities. Niosomes are preferred over liposomes because of the non-ionic surfactants higher stability lower cost and ease of storage compared to phospholipids. Surfactants do not require any particular handling or storage conditions. Niosomes act as a controlled and targeted drug delivery system that reduces toxicity and increases drug penetration into target tissues. The review article focused on several ideas including advantages and disadvantages of niosomal preparations niosome characteristics and its application.

Encapsulins: Structure, Properties, and Biotechnological Applications.

In 1994 a new class of prokaryotic compartments was discovered, collectively called "encapsulins" or "nanocompartments". Encapsulin shell protomer proteins self-assemble to form icosahedral structures of various diameters (24-42 nm). Inside of nanocompartments shells, one or several cargo proteins, diverse in their functions, can be encapsulated. In addition, non-native cargo proteins can be loaded into nanocompartments, and shell surfaces can be modified via various compounds, which makes it possible to create targeted drug delivery systems, labels for optical and MRI imaging, and to use encapsulins as bioreactors. This review describes a number of strategies of encapsulins application in various fields of science, including biomedicine and nanobiotechnologies.

The design strategy for pillararene based active targeted drug delivery systems.

Pillararenes have columnar architectures with electron-rich cavities to endow themselves with unique host-guest complexation capability. Easy structural modifiability facilitates them to be used in many applications. Currently, pillararene based drug delivery systems (DDSs) have been developed as a powerful tool for precise diagnosis and treatment of cancer. Various functional guest molecules could be integrated with pillararenes to construct nanomaterials for cancer chemotherapy, phototherapy and chemodynamic therapy. In order to improve cancer therapy efficacy, active targeted DDSs have become particularly important. Benefiting from the good host-guest properties and structural variability of pillararenes, tumor targeting groups could be easily introduced into pillararene based DDSs to realize precise drug delivery at tumor sites. In this feature article, we provide a comprehensive summary of the present design strategy for pillararene based active targeted DDSs, which can be classified into three types namely host-guest complexation, charge reversal and targeted group modified pillararenes. Some important examples are selected to for a detailed discussion on their respective strengths and weaknesses.

Macrophage-targeted nanoparticles mediate synergistic photodynamic therapy and immunotherapy of tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that poses a serious global public health threat. Due to the high incidence of adverse reactions associated with conventional treatment regimens, there is an urgent need for better alternative therapies. CpG oligodeoxynucleotides (CpG ODNs) are synthetic oligodeoxyribonucleotide sequences. They can induce a Th1-type immune response by stimulating Toll-like receptors (TLRs) in mammalian immune cells, thus killing Mtb. However, due to the negative charge and easy degradation of CpG ODNs, it is necessary to deliver them into cells using nanomaterials. PCN-224 (hereinafter referred to as PCN), as a metal-organic framework based on zirconium ions and porphyrin ligands, not only has the advantage of high drug loading capacity, but also the porphyrin molecule in it is a type of photosensitizer, which allows these nanocomposites to play a role in photodynamic therapy (PDT) while delivering CpG ODNs. In addition, since Mtb mainly exists in macrophages, targeting anti-TB agents to macrophages is helpful to improve the anti-TB effect. Phosphatidylserine (PS) is a biological membrane phospholipid that is normally found on the inner side of cell membranes in, for example, plant and mammalian cells. When apoptosis occurs, PS can flip from the inner side of the cell membrane to the surface of the cell membrane, displaying a specific "eat-me" signal that can be recognized by specific receptors on macrophages. Therefore, we can use this macrophage-targeting property of PS to construct bio-inspired targeted drug delivery systems. In this study, we constructed PCN-CpG@PS nanocomposites. PCN-CpG@PS, combining PDT and immunotherapy, is designed to target macrophages at the site of a lesion and kill latent Mtb. We physically characterized the nanocomposites and validated their bactericidal ability in vitro and their ability to stimulate the immune system in vivo. The results demonstrated that the targeted nanocomposites have certain in vitro antituberculosis efficacy with good safety.

Efficacy of pentamidine-loaded chitosan nanoparticles as a novel drug delivery system for Leishmania tropica.

The present study compares the in vitro effects of nanoparticles loaded pentamidine drug and conventional pentamidine on Leishmania tropica. Herein, pentamidine-loaded chitosan nanoparticles (PTN-CNPs) have been synthesized through an ionic gelation method with sodium tripolyphosphate (TPP). Next, the physical characteristics of PTN-CNPs were determined through the surface texture, zeta potential, in vitro drug release, drug loading content (DLC), and encapsulation efficacy (EE) and compared its efficacy with free pentamidine (PTN) drug against promastigotes and axenic amastigotes forms of L. tropica in vitro. The PTN-CNPs displayed a spherical shape having a size of 88 nm, an almost negative surface charge (-3.09 mV), EE for PTN entrapment of 86%, and in vitro drug release of 92% after 36 h. In vitro antileishmanial activity of PTN-CNPs and free PTN was performed against Leishmania tropica KWH23 promastigote and axenic amastigote using 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyletetrazolium bromide (MTT) assay. It was observed that the effect of PTN-CNPs and free PTN on both forms of the parasite was dose and time dependent. Free PTN presented low efficacy even at higher dose (40 µg/ml) with 25.6 ± 1.3 and 26.5 ±1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 hrs incubation. While PTN-CNPs showed strong antileishmanial effects on both forms of parasite with 16 ± 0.4 and 19 ± 0.7 mean viability rate at the same higher concentration (40 µg/ml) after 72 hrs incubation. Half maximal inhibitory concentration (IC50) values of PTN-CNPs toward promastigotes and amastigotes were obtained as 0.1375 µg/ml and 0.1910 µg/ml, respectively. In conclusion, PTN-CNPs effectively inhibited both forms of the L. tropica; however, its effect was more salient on promastigotes. This data indicates that the PTN-CNPs act as a target drug delivery system. However, further research is needed to support its efficacy in animal and human CL.

Formulation and evaluation of 5-fluorouracil controlled release chronotherapeutic drug delivery system (CTDDS) for colorectal cancer

Objective: As most of the drugs disintegrate and dissolve in stomach before reaching the target site and to substitute intravenous (IV) route based chrono modulated chemotherapy, oral colon target drug delivery system was formed. The aim of this study was to design, develop, and evaluate a colon targeted tablet containing 5-Fluorouracil (5-FU) to give a controlled release effect of drug for colonic cancer with a goal to increase the bioavailability and improve the patient compliance. Methods: Varied concentration of different polymers such as Xanthan gum and Eudragit were used to get an optimized formulation of 5-FU tablet. The prepared formulation was evaluated for pre compression and post compression parameters such as hardness, weight, friability and drug content uniformity. The optimized formulation was further evaluated by Fourier Transformed Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), in-vitro dissolution studies, dissolution kinetic modeling and stability analysis. Results: All pre-formulation tests were within range of USP standards. Friability of all tablets was satisfied. The interference of the polymers was ruled out by FTIR. In-vitro release studies of 5-FU tablets in phosphate buffer of pH 7.0 were performed using a modified diffusion cell that resulted sustained release (90.99% to 92.69% after 12h) and kinetic models depicted the combined diffusion and dissolution mechanism of release. The optimized tablets were found having only physical interactions based on DSC. The product was found stable when evaluated using accelerated stability studies. Conclusion: It was concluded from the studies that the colon target tablet of 5-FU prepared by different concentration of polymers were optimized and can be efficiently used to control the rate of drug release to the colon in the belief of improved therapeutic efficacy and tolerability. Therefore, it is a better alternative for intravenous route based chrono modulated chemotherapy.

Microfluidic synthesis of zoledronic acid loaded chitosan nanoparticles used for osteogenic differentiation of mesenchymal cells

Zoledronic acid (ZA) is known as a potent bisphosphonate in osteogenic differentiation, but at high doses, it possesses toxic effects and causes decreased proliferation and differentiation of osteoblasts. Therefore, encapsulation of ZA into nanoparticles and control of its release is expected to promote differentiation of stem cells into osteoblasts. The present work aimed to develop a simple method for synthesis of monodisperse ZA-loaded chitosan (CS) nanoparticles. In this regard, we proposed a microfluidic synthesis of nanoparticles through the ionic cross-linking of CS in the presence of ZA without a crosslinker. The main advantages of these microfluidic generated nanoparticles were narrow size distribution and fine spherical shape. Conversely, the nanoparticles that were synthesized using a bulk mixing method had an irregular shape with a broad size distribution. Real-time PCR assay as well as alizarin red staining were used to evaluate the in-vitro osteogenic potential of the nanoparticles. The results indicated that the controlled release of ZA from the microfluidic system generated uniform nanoparticles, improving the osteogenic differentiation of mesenchymal stem cells. Additionally, this microfluidic device provided the well-controlled synthesis of novel nanoparticles with a modified CS macromolecular polymer for targeted drug delivery systems.

Synthesis and characterization of silica nanoparticles from rice ashes coated with chitosan/cancer cell membrane for hepatocellular cancer treatment

Dual pH-sensitive smart nanocarriers based on silica nanoparticles (SNPs) extracted from rice husk ashes (RHAs) to effectively inhibit liver cancer cell proliferation were investigated. The SNPs were coated with chitosan (CH) and loaded with doxorubicin (DOX), then functionalized with cell membrane (CM) for homologous targeting ability. The FTIR spectra showed an absorption wave number at 1083 cm−1 which confirmed the existence of the SiOSi group, ratifying that the nanocarriers belong to silica species. The Korsmeyer-Peppas kinetic model reported R2 values of 0.996 and 0.931 for pH = 5.4 and pH = 7.4, respectively, demonstrating pH-responsive behavior of the nanocarriers. The cytotoxicity test confirmed that the HepG2 cell line treated with different SNP–CH–CM concentrations had no detectable significant cell toxicity, however, SNP–CH–DOX–CM induced greater cell death. In vivo tests revealed that SNP–CH–DOX–CM suppressed liver cancer growth in nude mice, demonstrating high pharmaceutical capability. Histological examination of vital organs showed that the targeted drug delivery system (DDS) had minor in vivo toxicity. In the light of its high treatment efficacy and minimal side effects, the investigated DDS is promising for the therapy of liver cancer.

Advancement of Niosomal Transdermal Targeting Drug Delivery System

Traditional methods for applying medications to the skin include a variety of methods. Transdermal has been a popular method of drug delivery in recent years for a variety of medications that are challenging to administer in other ways. Transdermal drug delivery has a number of benefits, chief among them the prevention of first-pass metabolism and the stomach environment, which would render the drug inactive. In addition to discussing in depth the various formulation techniques and permeability enhancement for improved therapeutic efficacy, this review covers the fundamental anatomy of the skin that is pertinent to the transdermal route as a drug delivery method. The evaluation sums up the technologies that are now available on the market and discusses the path they are headed in. A transdermal patch offers a controlled release of medicine into the patient, typically through either membrane pores casing a reserve of medication or over body heat melting thin layers of medication entrenched in the adhesive. This is a bonus of transdermal drug transport over different drug transport styles, including like oral, topical, I. V., I. M., etc. The skin is a very real barrier; in this way, drug molecules are modest enough to permeate the skin and can be administered in this way. Typically, the basic disadvantage of transdermal administration systems. Transdermal patches for a wide run of solutions are now readily available. With properties like improved penetration of drug, a sustained sedate discharge by local depot, and modulating systemic absorption of drugs through the skin by a membrane which limits rate, niosomes are vesicular nanocarriers that are getting to be more and more well known as a potential transdermal drug delivery framework. Niosomes are non-ionic surfactant-based vesicles that are more stable, biodegradable, and generally harmless. Niosomes are ideal to liposomes since surfactants are more chemically stable than lipids. The concept of niosome, its benefits and disadvantages, composition, method of preparation, variables influencing niosomes, definition and characterization, and use of niosome are the main topics of this review study. Niosomes can be used to treat a variety of illnesses, including psoriasis, leishmaniasis, cancer, migraines, Parkinson’s disease, etc. Niosomes can help in diagnosis. Niosomal administration can be done intramuscularly, intravenously, orally, or it can be used topically.

Acute Toxicity Study of Intravenously Administered Capecitabine Resealed Erythrocytes in Mice

Introduction:- Capecitabine resealed erythrocytes were prepared as a potential targeted drug delivery system for the treatment of hepatocellular carcinoma. This system has been developed to increase the therapeutic efficacy of drug and to reduce its adverse effects. This paper demonstrated the acute toxicity study of the formulation in Swiss albino mice. Methodology:- Dose of Capecitabine was 2000 mg/kg orally with zero toxicity as per the previous studies. The doses of formulation selected were 1/5th, 1/10th, 1/20th of the oral dose calculated on the basis of the % encapsulation efficiency of drug in formulation. The doses were given intravenously in single dose in mice tail vein. All the animals were observed for 14 days period for mortality, behavioral symptoms and locomotor activity. Results:- After sacrification of animals, serum was collected to analyze hematological and biochemical parameters. The isolated liver was observed for histopathological changes in mice. Here, we found that all the three to be selected would be safe for further in- vivo screening of Hepatocellular carcinoma. Conclusion:- So, we concluded that, all the three doses of formulation low (0.90mg/kg), medium (1.79mg/kg) and high (3.58mg/kg) with no signs of mortality, behavioural changes and no necrosis in liver histopathology. This revealed that, all the three selected doses were safe for further in vivo studies.

Exosomes derived from lung cancer cells: Isolation, characterization, and stability studies

Recent advances in nanomedicine have paved the way for developing targeted drug delivery systems. Nanoscale exosomes are present in almost every body fluid and represent a novel mechanism of intercellular communication. Because of their membrane origin, they easily fuse with cells, acting as a natural delivery system and maintaining the bioactivity and immunotolerance of cells. To develop a reconstitutable exosome-based drug candidate for clinical applications, quality assurance by preserving its physical and biological properties during storage is necessary. Therefore, this study aimed to determine the best storage conditions for exosomes derived from lung cancer cells (A549). This study established that the phosphate-buffered saline buffer enriched with 25 mM trehalose is an optimal cryoprotectant for A549-derived exosomes stored at −80°C. Under these conditions, the concentration, size distribution, zeta potential, and total cargo protein levels of the preserved exosomes remained constant.

Probing the interaction of zinc oxide nanorods with human serum albumin: A spectroscopic approach

Bio-functionalized metal oxide nanoparticles (NPs) have been taken great importance in biomedical fields. The use of nanoparticles as delivery agents of therapeutic molecules led the researchers to emphasize the potential impact of these NPs on bio-macromolecules as protein–nanoparticle complexes, which also extended their importance as vehicles in targeted drug delivery systems due to increased ease of administration, firmness, reduced toxic side effects, and half-life of drugs. Since human serum albumin is the blood protein responsible for transporting materials in the blood system, the interaction of these particles with HSA is essential to be understood before considering the nanoparticles for any individual biomedical application. In the present study, we synthesized zinc-oxide nanorods (ZONRs) using a microwave-assisted synthesis technique, and characterized them by XRD, FTIR, Raman, SEM-EDX, UV-Vis spectroscopy, and photoluminescence (PL) spectroscopy methods. The interaction studies were carried out using fluorescence spectroscopy, and the change in secondary structure was analyzed using CD spectroscopy. The results of MTT cell viability assay demonstrated that the ZONRs has potential cytotoxic properties.

Niosomes-loaded selenium nanoparticles as a new approach for enhanced antibacterial, anti-biofilm, and anticancer activities

Targeted drug delivery and increasing the biological activity of drugs is one of the recent challenges of pharmaceutical researchers. Niosomes are one of the new targeted drug delivery systems that enhances the biological properties of drugs. In this study, for the first time, the green synthesis of selenium nanoparticles (SeNPs), and its loading into niosome was carried out to increase the anti-bacterial and anti-cancer activity of SeNPs. Different formulations of noisome-loaded SeNPs were prepared, and the physical and chemical characteristics of the prepared niosomes were investigated. The antibacterial and anti-biofilm effects of synthesized niosomes loaded SeNPs and free SeNPs against standard pathogenic bacterial strains were studied, and also its anticancer activity was investigated against breast cancer cell lines. The expression level of apoptotic genes in breast cancer cell lines treated with niosome-loaded SeNPs and free SeNPs was measured. Also, to evaluate the biocompatibility of the synthesized niosomes, their cytotoxicity effects against the human foreskin fibroblasts normal cell line (HFF) were studied using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results illustrated that the optimal formulation had an average size of 177.9 nm, a spherical shape, and an encapsulation efficiency of 37.58%. Also, the results revealed that the release rate of SeNPs from niosome-loaded SeNPs and free SeNPs was 61.26% and 100%, respectively, in 72 h. Also, our findings demonstrated that the niosome-loaded SeNPs have significant antibacterial, anti-biofilm, and anticancer effects compared to the free SeNPs. In addition, niosome-loaded SeNPs can upregulate the expression level of Bax, cas3, and cas9 apoptosis genes while the expression of the Bcl2 gene is down-regulated in all studied cell lines, significantly. Also, the results of the MTT test indicated that the free niosome has no significant cytotoxic effects against the HFF cell line which represents the biocompatibility of the synthesized niosomes. In general, based on the results of this study, it can be concluded that niosomes-loaded SeNPs have significant anti-microbial, anti-biofilm, and anti-cancer effects, which can be used as a suitable drug delivery system.

Facile Fabrication of Methyl Gallate Encapsulated Folate ZIF-L Nanoframeworks as a pH Responsive Drug Delivery System for Anti-Biofilm and Anticancer Therapy.

Zeolitic imidazole frameworks are emerging materials and have been considered an efficient platform for biomedical applications. The present study highlights the simple fabrication of methyl gallate encapsulated folate-ZIF-L nanoframeworks (MG@Folate ZIF-L) by a simple synthesis. The nanoframeworks were characterized by different sophisticated instruments. In addition, the drug-releasing mechanism was evidenced by in vitro releasing kinetics at various pH conditions. The anti-biofilm potential confirmed by the biofilm architectural deformations against human infectious pathogens MRSA and N7 clinical strains. Furthermore, anticancer efficacy assessed against A549 lung cancer cells. The result reveals that the MG@Folate ZIF-L exposed a superior cytotoxic effect due to the pH-responsive and receptor-based drug-releasing mechanism. Based on the unique physicochemical and biological characteristics of nanoframeworks, it has overcome the problems of undesired side effects and uncontrolled drug release of existing drug delivery systems. Finally, the in vitro toxicity effect of MG@Folate ZIF-L was tested against the Artemia salina (A. salina) model organism, and the results show enhanced biocompatibility. Overall, the study suggested that the novel MG@Folate ZIF-L nanoframeworks is a suitable material for biomedical applications. It will be very helpful to the future design for targeted drug delivery systems.

Micelle-Based Nanocarriers for Targeted Delivery of Cargo to Pancreas.

Innovations in the field of amphiphilic block copolymers have led to the development of a series of attractive polymer-based drug and gene delivery micellar formulations. The amphiphilic block copolymers' low critical micelle concentration (CMC) results in highly stable nanoscale micelles possessing favorable in vivo safety profiles and biocompatibility, making them an excellent carrier choice for the systemic administration of various poorly soluble drugs. These micelles can also be used as an actively targeted drug delivery system. The targeting is achieved by conjugating specific targeting ligand molecules to the micelle surface. The conjugation takes place at the hydrophilic termini of the copolymers, which forms the shell or surface of the nanomicelles. In our lab, we have developed a targeted Pluronic® F127-based nanoformulation to achieve targeting of specific cell types in the pancreas. To achieve active targeting based on the desired end application, we have conjugated several monoclonal antibodies (~150kDa IgG) reactive to specific cell types in the pancreas by coupling lysine amino groups of the antibody to the p-nitrophenyl carbonate groups generated on the hydrophilic PEO segments of the Pluronic® F127. The resultant targeted nanomicelles demonstrated high binding specificity and targeting efficiency. These nanomicelles can be used to encapsulate and deliver hydrophobic imaging agents and/or water-insoluble therapeutic small molecules to specific pancreatic cell types, enabling the development of diverse tools for use in the diagnosis and/or treatment of pancreas pathologies.

Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer

Multi-modal synergistic therapy, especially the integration of near-infrared laser phototherapies and chemotherapy, is often sought after owing to its minimal invasiveness, low side effects, and improved anticancer therapeutic efficacy. Herein, CuS nanoparticles were first coated with zinc phthalocyanine derivant (Pc)-functionalized mesoporous silica (mSiO2-Pc) to achieve a drug delivery system (CuS@mSiO2-Pc) with photothermal/photodynamic therapy. Chemical drug DOX was subsequently loaded for chemotherapy, and hyaluronic acid (HA) was employed as a covering material with cancer targeting. The as-obtained CuS@mSiO2-Pc(DOX)@HA nanoparticles were nano-sized with good biocompatibility, effective DOX loading, and controllable DOX releasing. Expectedly, this multifunctional nanoplatform exhibits effective generation of reactive oxygen species and hyperthermia upon the near-infrared laser irradiation. Most importantly, the nanoparticles were targeted into 4T1 cells and showed significantly remarkable cytotoxicity under near-infrared laser irradiation, proving their synergistic therapeutic efficacy. Therefore, this targeted drug system based on CuS with synergistic photothermal therapy/photodynamic therapy/chemotherapy has great application prospects in clinical anticancer treatment for triple negative breast cancer.