Targeted Drug Delivery Systems Research Articles

Development of Targeted Drug Delivery System for the Treatment of SARS-CoV-2 Using Aptamer-Conjugated Gold Nanoparticles

Background: The SARS-CoV-2 pandemic has highlighted niclosamide (NIC) as a promising treatment for COVID-19. However, its clinical application is limited due to its poor water solubility, resulting in low bioavailability. Methods: To address this issue, we developed a AuNP-HA-NIC system, which combines gold nanoparticles with hyaluronic acid to enhance drug delivery. Our comprehensive characterization of the system revealed that hyaluronic acid with specific molecular weights, particularly those exposed to electron-beam irradiation between 2 and 20 kGy, produced the most stable nanoparticles for efficient drug loading and delivery. Results: Additionally, the AuNP-HA-NIC system exhibits a significant sensitivity to pH changes, which is a critical feature for targeted drug release. Under acidic conditions mimicking the stomach and small intestine, minimal drug release was observed, indicating the effective prevention of premature drug release in the gastrointestinal tract. Furthermore, the integration of a targeting aptamer established specific binding abilities towards the SARS-CoV-2 spike protein, distinguishing it from other coronaviruses. Conclusions: As research progresses, and with further in vivo testing and optimization, the AuNP-HA-NIC–aptamer system holds great promise as a game-changer in the field of antiviral therapeutics, particularly in the battle against COVID-19.

Dual-Responsive Alginate/PNIPAM Microspheres Fabricated by Microemulsion-Based Electrospray.

Smart materials for drug delivery are designed to offer a precise and controlled release of therapeutic agents. By responding to specific physiological stimuli, such as changes in temperature and pH, these materials improve treatment efficacy and minimize side effects, paving the way for personalized therapeutic solutions. In this study, we present the fabrication of dual-responsive alginate/poly(N-isopropylacrylamide) (PNIPAM) microspheres, having the ability to respond to both pH and temperature variations and embedding the lipophilic bioactive compound Ozoile. Ozoile® Stable Ozonides is obtained from extra virgin olive oil and acts as an inducer, interacting with major biological pathways by means of modulating the systemic redox balance. The dual-responsive microspheres are prepared by electrospray technique without the use of organic solvents. PNIPAM is synthesized by radical polymerization using the APS/TEMED redox initiators. The microspheres are further optimized with a chitosan coating to enhance their stability and modulate the degradation kinetics of the gel matrix. A comprehensive morphological analysis, Fourier transform infrared (FTIR) spectroscopy, and degradation assays are conducted to confirm the structural stability and pH-responsive behavior of the hydrogel microspheres. A study of the volume phase transition temperature (VPTT) by differential scanning calorimetry (DSC) is used to assess the microsphere thermal response. This research introduces a promising methodology for the development of targeted drug delivery systems, which are particularly useful in the context of oxidative stress modulation and inflammation management.

Anticancer Activities of Synthesized Niosome Nanoparticles Using Artemisia Annua Extract: Caspase3 and Caspase9 Apoptosis Gene Expression Analysis in Breast Cancer Cell Line (MCF-7)

Introduction: Pharmaceutical formulation of nanoparticles is widely used due to achieving targeted and stable drug release, improving drug solubility and reducing side drug reactions. One of the ways to improve the survival of cancer patients is the treatment using nanocarriers for anticancer drugs. The aim of this study was to synthesize encapsulated nisomes containing the extract of the Artemisia annua and investigate the anticancer and apoptotic effects against breast cancer cell lines. Methods: In this study, a Niosomes nanocarrier was made and then the extract of Gondwash herb was loaded into it. Its physical and chemical properties were confirmed using SEM, dynamic light scattering (DLS) and zeta potential. Likewise, the encapsulation percentage and release pattern of the extract were investigated. Finally, its anticancer effects against the breast cancer cell line (MCF_7) were investigated and the expression level of apoptotic genes Caspase3 and Caspase9 was studied using Real Time PCR method. At the end, statistical analysis was done by GraphPad Prism software, and cytotoxicity and gene expression data were analyzed by one-way analysis of variance. Results: The findings showed that the synthesized nanocarrier newsom containing the extract had a spherical structure and its size was 208.1 nanometers, the encapsulation percentage was 62.35% and the surface charge was 22.5. Similarly, newsome nanocarrier containing the extract had significant anticancer effects compared to the free extract and increased the expression of caspase 3 and caspase 9 genes by 1.184 ± 0.34 (P<0.05) and 1.68 ± 0.81, respectively. (P<0.05). Conclusion: The results showed that the nisome containing the extract of the Gondwash herb increases the anti-cancer and apoptotic effects significantly, and therefore, with further studies in the future, nisome can be used as a targeted drug delivery system for anti-cancer purposes.

ROS-responsive nanomicelles encapsulating celastrol ameliorate pressure overload-induced cardiac hypertrophy by regulating the NF-κB signaling pathway

Celastrol (CEL) belongs to the group of non-steroidal immunosuppressants with the potential to improve cardiac hypertrophy (CH). However, the poor biocompatibility and low bioavailability of CEL limit its in vivo application. This study was aimed to develop a targeted drug delivery system that can efficiently and safely deliver CEL to target tissues, providing a research basis for the application of CEL in CH therapy. A novel ROS-sensitive drug-loaded nanomicelle, dodecanoic acid (DA)-phenylboronic acid pinacol ester-dextran polymer encapsulating CEL (DBD@CEL), was synthesized using chemical synthesis. Then, the morphology, particle size, drug-loaded content, and ROS-responsive release behavior of DBD@CEL were studied. Pharmacokinetics and biocompatibility were evaluated using healthy mice. Finally, the ability and mechanism of DBD@CEL in improving CH in vivo were investigated using a mouse CH model. DBD@CEL was successfully prepared with a drug loading of 18.9%. It exhibited excellent stability with an average particle size of 110.0 ± 1.7 nm. Within 48 h, DBD@CEL released only 19.4% in the absence of H2O2, while in the presence of 1 mM H2O2, the release rate increased to 71.5%. Biocompatibility studies indicated that DBD@CEL did not cause blood cell hemolysis, had no impact on normal organs, and did not result in abnormal blood biochemical indicators, demonstrating excellent biocompatibility. In vivo studies revealed that DBD@CEL regulated the activation of NF-κB signaling, inhibits pyroptosis and oxidative stress, and thereby ameliorates CH. The ROS-responsive DBD@CEL nanodrug delivery system enhances the therapeutic activity of CEL for CH, providing a promising drug delivery system for the clinical treatment of CH.

Novel Carbohydrate Polymer-Based Systems for Precise Drug Delivery in Colon Cancer: Improving Treatment Effectiveness With Intelligent Biodegradable Materials.

Due to their biocompatibility, biodegradability, and controlled release, carbohydrates polymers are crucial to targeted drug delivery systems, notably for colon cancer treatment. This article examines how carbohydrate polymers like chitosan, pectin, guar gum, alginate, hyaluronic acid, dextran, and chondroitin sulfate are used in improved drug delivery. Modifying these polymers improves drug loading, stability, and release patterns, enhancing chemotherapeutic drugs' therapeutic index. Chitosan nanoparticles are pH-responsive, making them perfect for cancer treatment. Pectin's resistance to gastric enzymes and colonic bacteria makes it a promising colon-specific medication delivery agent. The combination of these polymers with nanotechnology, 3D printing, and AI allows the creation of stimuli-responsive systems that release drugs precisely in response to environmental signals like pH, redox potential, or colon enzymatic activity. The review highlights intelligent delivery system design advances that reduce systemic toxicity, improve treatment efficacy, and improve patient adherence. Carbohydrate polymers will revolutionize colon cancer treatment with personalized and accurate alternatives.

Targeted Drug Delivery Systems In Nanomedicine: Enhancing Therapeutic Efficacy In Oncology And Beyond

Targeted Drug Delivery Systems In Nanomedicine: Enhancing Therapeutic Efficacy In Oncology And Beyond

Twenty years of in vitro nanotoxicology: how AI could make the difference.

More than two decades ago, the advent of Nanotechnology has marked the onset of a new and critical field in science and technology, highlighting the importance of multidisciplinary approaches to assess and model the potential human hazard of newly developed advanced materials in the nanoscale, the nanomaterials (NMs). Nanotechnology is, by definition, a multidisciplinary field, that integrates knowledge and techniques from physics, chemistry, biology, materials science, and engineering to manipulate matter at the nanoscale, defined as anything comprised between 1 and 100nm. The emergence of nanotechnology has undoubtedly led to significant innovations in many fields, from medical diagnostics and targeted drug delivery systems to advanced materials and energy solutions. However, the unique properties of nanomaterials, such as the increased surface to volume ratio, which provides increased reactivity and hence the ability to penetrate biological barriers, have been also considered as potential risk factors for unforeseen toxicological effects, stimulating the scientific community to investigate to which extent this new field of applications could pose a risk to human health and the environment.

A Review on the Progress of QbD Approach in Nanosystems Optimization: Current Updates and Strategic Applications

: Nanotechnology has made great strides in developing targeted drug delivery systems over the past few decades. These systems have garnered attention for their unique biological properties and ability to deliver drugs in a stable and sustainable manner. Despite these advances, there are still concerns about quality, efficacy, and safety. Many fabrication techniques still need to be refined to address the complex structures and non-standard manufacturing processes that can impact the quality of drug delivery systems. Recently, optimization techniques such as Quality by Design (QbD) have gained popularity in the pharmaceutical industry. QbD is a structured approach that addresses many technological and trait-related issues by providing a deep understanding of the product and its operations. This review examines the current state of QbD in the design of various nano-drug delivery systems, including lipid nanoparticles, lipid carriers, nano micelles, beaded drug delivery systems, nanospheres, cubosomes, and novel cosmeceuticals. Various mathematical models and statistical tests have been used to identify the parameters that influence the physical characteristics of these nanosystems. Critical process attributes such as particle size, yield, and drug entrapment have been studied to assess risk factors during development. However, critical process parameters are often identified through trial and error. This review highlights common material attributes and process parameters that affect the quality of nano-drug delivery systems. Hence, this survey has disclosed the various material attributes and process parameters, quality variables of different nano-drug systems. QbD designs such as Central drug composite, Design of experiment, D-optimal Design, Box-Benkhen Design, and Face center Design in optimizing the nanosystems have also been added. Conclusively, QbD optimization in nano drug delivery systems is expected to be a time-honored strategy in the forthcoming years.

Nanotechnology in Malaria Treatment: Targeted Drug Delivery Systems and Future Applications

Malaria continued to be a major global health challenge, particularly in regions with high disease burden, despite advancements in treatment options such as Artemisinin-based Combination Therapies (ACTs). The emergence of nanotechnology offered a transformative approach to malaria treatment, with its potential to improve drug delivery, bioavailability, and therapeutic outcomes. This review examined the current applications and advancements in nanotechnology for malaria treatment, focusing on the use of nanocarriers like liposomes, polymeric nanoparticles, and solid lipid nanoparticles. These systems enhanced the efficacy of antimalarial drugs by enabling targeted delivery to malaria-infected cells, overcoming drug resistance, and offering controlled release mechanisms. The review also explored emerging strategies such as combination therapies, personalized nanomedicine, responsive nanoparticles, and vaccine delivery systems. While nanotechnology holds great promise, challenges including safety, scalability, regulatory hurdles, and cost were addressed. Future directions suggest innovations such as smart nanocarriers, personalized treatments, and enhanced diagnostic integration. Methodologically, this review synthesized data from recent preclinical and clinical research to provide a comprehensive analysis of nanotechnology’s role in advancing malaria treatment. Global collaboration and interdisciplinary research will be pivotal in realizing the full potential of nanotechnology in combating malaria. Keywords: Nanotechnology, malaria treatment, drug delivery systems, liposomes, nanoparticles, targeted therapy, drug resistance

Polypeptides-Based Nanocarriers in Tumor Therapy.

Cancer remains a worldwide problem, and new treatment strategies are being actively developed. Peptides have the characteristics of good biocompatibility, strong targeting, functional diversity, modifiability, membrane permeable ability, and low immunogenicity, and they have been widely used to construct targeted drug delivery systems (DDSs). In addition, peptides, as endogenous substances, have a high affinity, which can not only regulate immune cells but also work synergistically with drugs to kill tumor cells, demonstrating significant potential for application. In this review, the latest progress of polypeptides-based nanocarriers in tumor therapy has been outlined, focusing on their applications in killing tumor cells and regulating immune cells. Additionally, peptides as carriers were found to primarily provide a transport function, which was also a subject of interest to us. At the end of the paper, the shortcomings in the construction of peptide nano-delivery system have been summarized, and possible solutions are proposed therein. The application of peptides provides a promising outlook for cancer treatment, and we hope this article can provide in-depth insights into possible future avenues of exploration.

An Overview of Nanotechnology in Dental Medicine

The dentistry industry has been modernized by nanotechnology, as this emerging field has opened up new doors for dental treatment, restoration, and tissue regeneration. The potential applications of nanomaterials in dentistry are reviewed in this paper, ranging from advanced restorative materials to targeted drug delivery systems. Due to their unique characteristics (e.g., high surface area-to-volume ratios and tunable physicochemical properties), nanomaterials allow for the precise control of material behavior at the nanoscale. The ability of nanostructured materials to promote tissue regeneration offers the prospect of developing new approaches in bone and periodontal regeneration. Therefore, this review thoroughly analyzes nanomaterials’ characteristics and biomedical applications, highlighting how they can aid in overcoming challenges in dental care and create possibilities for more individualized and less-invasive dental treatments.

Development of Dual-Targeted Mixed Micelles Loaded with Celastrol and Evaluation on Triple-Negative Breast Cancer Therapy.

Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC.

Hyaluronic acid-coated polypeptide nanogel enhances specific distribution and therapy of tacrolimus in rheumatoid arthritis

Rheumatoid arthritis (RA) involves chronic inflammation, oxidative stress, and complex immune cell interactions, leading to joint destruction. Traditional treatments are often limited by off-target effects and systemic toxicity. This study introduces a novel therapeutic approach using hyaluronic acid (HA)-conjugated, redox-responsive polyamino acid nanogels (HA-NG) to deliver tacrolimus (TAC) specifically to inflamed joints. The nanogels’ disulfide bonds enable controlled TAC release in response to high intracellular glutathione (GSH) levels in activated macrophages, prevalent in RA-affected tissues. In vitro results demonstrated that HA-NG/TAC significantly reduced TAC toxicity to normal macrophages and showed high biocompatibility. In vivo, HA-NG/TAC accumulated more in inflamed joints compared to non-targeted NG/TAC, enhancing therapeutic efficacy and minimizing side effects. Therapeutic evaluation in collagen-induced arthritis (CIA) mice revealed HA-NG/TAC substantially reduced paw swelling, arthritis scores, synovial inflammation, and bone erosion while suppressing pro-inflammatory cytokine levels. These findings suggest that HA-NG/TAC represents a promising targeted drug delivery system for RA, offering potential for more effective and safer clinical applications.

Stem Cell-Nanodiamond Synergy: Efficacy in Breast Cancer

In the intricate and evolving landscape of oncological research and therapeutic modalities, the imperative for sophisticated, precise, and holistic strategies becomes paramount, especially within the intricate realm of breast cancer management. This analytical discourse undertakes a comprehensive examination of the synergistic interplay between stem cells and nanodiamonds, unveiling their collective potential to pioneer transformative therapeutic paradigms. Within the confines of this discussion, stem cells are acknowledged for their intrinsic adaptability and potent regenerative properties, whereas nanodiamonds are recognized for their versatile functions in targeted drug delivery systems and their inherent biocompatibility. Individually, they embody diverse therapeutic prospects; however, it is their collaborative interaction that is positioned at the vanguard of this evaluative discourse. The elaborate biophysical and biochemical exchanges incited by the amalgamation of stem cells’ regenerative prowess and nanodiamonds’ precision in drug conveyance are meticulously analyzed. This analysis transcends conventional scrutiny, delving into the profound molecular mechanisms, cellular kinetics, and resultant clinical ramifications, thereby delineating a comprehensive blueprint for an integrated therapeutic strategy.

Reactive oxygen species (ROS)-responsive biomaterials for treating myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a critical issue that arises when restoring blood flow after an ischemic event in the heart. Excessive reactive oxygen species (ROS) production during this process exacerbates cellular damage and impairs cardiac function. Recent therapeutic strategies have focused on leveraging the ROS microenvironment to design targeted drug delivery systems. ROS-responsive biomaterials have emerged as promising candidates, offering enhanced therapeutic efficacy with reduced systemic adverse effects. This review examines the mechanisms of ROS overproduction during myocardial ischemia-reperfusion and summarizes significant advancements in ROS-responsive biomaterials for MIRI treatment. We discuss various chemical strategies to impart ROS sensitivity to these materials, emphasizing ROS-induced solubility switches and degradation mechanisms. Additionally, we highlight various ROS-responsive therapeutic platforms, such as nanoparticles and hydrogels, and their unique advantages in drug delivery for MIRI. Preclinical studies demonstrating the efficacy of these materials in mitigating MIRI in animal models are reviewed, alongside their mechanisms of action and potential clinical implications. We also address the challenges and future prospects of translating these state of the art biomaterial-based therapeutics into clinical practice to improve MIRI management and cardiac outcomes. This review will provide valuable insights for researchers and clinicians working on novel therapeutic strategies for MIRI intervention.

Carbon Nanotubes an Excellent Targeted Drug Delivery System

Carbon nanotubes, or CNTs, are carbon allotropes with a nanostructure that can have a length-to-breadth proportion more prominent than 1,000,000. These round and hollow carbon particles have exceptional properties that make them possibly helpful in an assortment of nanotechnology applications. CNTs might be joined with a scope of natural components, including proteins, drugs, and nucleic acids, to give bio-functionalities. CNTs come in two assortments: multi-walled (MWNTs) and single-walled (SWNTs). Among its captivating properties are its high viewpoint proportion, strength, lightweight weight, high warm conductivity, and electrical attributes that reach from metallic to semiconducting. Carbon nanotubes might be made by various cycles, including warm blend, substance fume statement, laser removal, circular segment release dissipation, plasma-based union, and synthetic fume affidavit increased by plasma. Carbon nanotubes (CNTs) track down use in drug conveyance, blood malignant growth, bosom disease, cerebrum malignant growth, liver malignant growth, cervical malignant growth, quality treatment, resistant therapy, biomedical imaging, biosensors, and tissue designing. The noncovalent functionalization of specific MNTs with folic corrosive (FA) worked on the vehicle of medication to malignant growth cells in the lymph hubs. By utilizing a remotely introduced magnet to guide the medication lattice to the provincial designated lymph hubs, the MNTs can ceaselessly deliver chemotherapeutic medications for a few days while remaining in the depleting designated lymph hubs. Growth cells communicating folate receptors (FRs) in the lymph hubs can be explicitly obliterated since FRs are overexpressed in different human malignancies.

Advancing Ovarian Cancer Therapeutics: The Role of Targeted Drug Delivery Systems.

Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.

Unlocking the Potential of Drug Delivery Systems: A Comprehensive Review of Formulation Strategies and Technologies in the Field of Pharmaceutics

: The creation of innovative drug delivery systems to enhance therapeutic effectiveness, safety, and patient compliance has resulted in considerable developments in pharmaceutics in recent years. The most recent formulation techniques and technologies are reviewed in this article to improve medication distribution and accomplish specific therapeutic goals. : This article thoroughly summarizes the most recent formulation techniques and technologies used to enhance medication delivery and provide specific therapeutic effects. It discusses the variety of medication delivery methods, including nanoparticles, liposomes, micelles, and dendrimers, and explores the application of nanotechnology and biotechnology in drug delivery. Additionally, the paper emphasizes the significance of targeted drug delivery systems and their capacity to cross biological barriers including the blood-brain barrier and tumor microenvironment. : The review also addresses the challenges faced in developing and commercializing drug delivery systems and suggests potential solutions to overcome them. Furthermore, the article emphasizes the role of computational modeling and simulation in designing and optimizing drug delivery systems. : Overall, this review paper offers insightful information for pharmaceutics researchers, scientists, and practitioners that will help in the creation of novel drug delivery systems that improve patient outcomes and quality of life.

Chemo-Enzymatic Functionalization of Bovine Milk Exosomes with an EGFR Nanobody for Target-specific Drug Delivery.

Bovine milk exosomes (BmExo) have been identified as versatile nanovesicles for anti-cancer drugs delivery due to their natural availability and biocompatibility. However, tumor-specific delivery based on BmExo often requires post-isolation modifications of the membrane surface with active-targeting ligands. In this study, we report an alternative approach to functionalize BmExo with nanobody combining facile chemical modification and Sortase A-mediated site-specific ligation, as demonstrated by the development of an epidermal growth factor receptor (EGFR)-targeted drug delivery system. The BmExo membrane was first coated with a diglycine-containing amphiphile molecule, NH2-GG-PEG2000-DSPE, by hydrophobic insertion. The diglycine as nucleophiles displayed on the membrane enabled the subsequent ligation of the EGFR nanobody (7D12) by Sortase A (SrtA)-mediated site-specific transpeptidation. The successful construction of BmExo-7D12 was confirmed by Western blotting analysis, electron microscopy, and dynamic light scattering (DLS). As a demonstration model, BmExo-7D12 loaded with the chemotherapeutic drug doxorubicin (Dox) was shown to be able to deliver Dox to cancer cells in response to the expression of EGFR as manifested by immunocytochemistry and flow cytometry analysis. Finally, the cytotoxicity assay showed that BmExo-7D12-Dox was more effective in killing tumor cells with high EGFR expression while significantly reduced the non-specific toxicity to EGFR negative cells. In conclusion, these results demonstrate that 7D12-functionalized BmExo can serve as a target-specific delivery system for Dox to selectively kill EGFR-expressing tumor cells. This approach should prove to be versatile and efficient for the generation of protein-ligands modified BmExo.

Multi-Sensitive Au NCs/5-FU@Carr-LA Composite Hydrogels for Targeted Multimodal Anti-Tumor Therapy.

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.