Journal of Drug Targeting最新文献

The combination therapy strategy exerts a significant anti-tumour effect by synergistically eliminating tumour cells through the use of two or more treatments. Nanomedicine delivery systems are widely employed in cancer therapy owing to their ability to effectively improve drug solubility and enhance drug targeting. To this end, we have designed and developed a nano-targeted drug delivery platform PAE-PEG-ss-Ce6/DOX nanoparticles (PPCD NPs), for the co-delivery of the photosensitiser chlorin e6 (Ce6) and the chemotherapeutic agent doxorubicin (DOX). The nanoparticles exhibit a mean particle size of 128.74 ± 0.80 nm, demonstrating excellent serum stability and pH/glutathione (GSH)-responsive release characteristics in vitro. Compared to monotherapy, PPCD NPs exhibited enhanced cytotoxicity and cellular uptake, effectively inhibiting cell proliferation by inducing reactive oxygen species (ROS) production. The results of the immunogenic cell death (ICD) experiments demonstrated that PPCD NPs induced a robust ICD effect through the synergistic action of DOX and Ce6, thereby activating anti-tumour immunity and achieving combination therapy. In vivo experiments and histopathological analysis demonstrated that PPCD NPs exhibit excellent tumour targeting, high anti-tumour efficacy and low biotoxicity. These findings demonstrated the superiority of the phototherapy-chemotherapy-immunotherapy synergistic treatment strategy and indicate that PPCD NPs hold promise as a safe and effective anti-tumour nanoscale targeted drug delivery system.

Gastrointestinal tumours pose a significant threat to human health. Small extracellular vesicles (sEVs) have emerged as a promising approach for drug delivery in the treatment of gastrointestinal tumours. sEVs exhibit intrinsic advantages over synthetic nanoparticles, including native targeting ligands, the ability to cross biological barriers via membrane fusion, and reduced immune clearance mediated by surface CD47, thereby overcoming limitations of conventional nanocarriers such as rapid opsonisation and hepatic sequestration. These minute vesicles are surrounded by a stable phospholipid bilayer and can be engineered with specific targeting ligands or loaded with diverse therapeutic cargoes, thereby overcoming the limitations of conventional drug delivery systems (DDSs) and improving tumour-specific accumulation while minimising off-target effects. In this review, we explore the recent advancements in sEV-based DDSs, with a focus on design approaches for engineered sEVs, immunotherapy-related engineered sEVs technologies and the utilisation of engineered sEVs in gastrointestinal tumours. Additionally, we discuss the current challenges and future prospects of sEV-based DDSs in clinical practice, underscore the innovative role of engineered sEVs in cancer therapy, and provide promising avenues for enhancing the treatment of gastrointestinal tumours and improving patient outcomes.

Background: Prognostic therapy for treating cutaneous wounds requires information about antioxidants and clotting factors in the tissue-remodeling phases.

Purpose: To find the differential expression of potential biomarkers in diabetic rat wounds post-healing after confirming the stability of Mentha piperita-silver nanoparticles (MPAgNPs).

Methods: MPAgNPs were characterized, and their bioactive compounds were identified by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) is used to find differential protein expression in diabetic healed rat skin, followed by Quantitative Reverse transcriptase polymerase chain reaction (qRT-PCR) for their confirmation.

Results: Scanning and transmission electron microscopy revealed spherical core metallic sizes of 50 nm. Dynamic light scattering determines the MPAgNPs' hydrodynamic size of 127 nm. The zeta potential value of -15.4 mV confirmed the NP's stability. Medioresinol, rosmarinic acid, caffeic acid, salvianolic acid, and methyl syringate were the bioactive compounds identified in M. piperita by LC-MS/MS. SDS-PAGE shows differential expression of anti-inflammatory, anti-apoptotic, antioxidant, and defense proteins. Antioxidant assays show increased levels of superoxide dismutase and glutathione peroxidase with decreased malondialdehyde. qRT-PCR confirmed enhanced expression of transforming growth factor, Thrombin, and Glutathione S-transferase P. At the same time, Tumor necrosis factor alpha, and Interleukin show reduced expression 16-D after MPAgNPs treatment.

Topical administration provides direct way for nanoparticles (NPs) to reach the tumour surface, inducing a more localised and direct therapeutic effect than what intravenous therapy can do and meanwhile guaranteeing higher biosafety. By leveraging the unique surface structure of tumours, these particles undergo intracavity diffusion and afterwards targeted transport into the tumour tissue, which is termed as the enhanced surface permeability and retention (ESPR) effect. Importantly, the ESPR effect of intracavity nanoparticles via topical administration does not rely on tumour-targeted ligand-receptor interactions. In this review, the current clinical status of topical administration-based therapy is updated, the mechanism of the ESPR effect is elucidated and how to modulate the ESPR effect is summarised.

Viral diseases damage the host's cells and weaken the host's immunity, leading to multiple relapses or lasting a long time. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a prevalent infection that can cause immunostimulation, serious medical complications or even promote the risk of side effects and fatality, especially among older adults. Due to the replication process of the viral genome, it is significant to design and develop new pharmaceuticals to alleviate the illness and global death rates attributed to infection. Chitosan, a versatile biopolymer derived from natural sources, possesses cationic properties and has been employed to produce nanoparticles (NPs). These NPs exhibit biocompatibility, biodegradability, antimicrobial and anticancer properties, non-toxicity, ready availability, and the ability to function as drug delivery systems (DDSs). The physicochemical attributes of chitosan and its NPs in the transfer of bioactive agents are detected in nanotechnology, which can enhance anti-viral efficacy. This review highlights progressions in nanoscience for chitosan-based drug delivery in treating viral diseases. New research is expected to suggest new strategies in the field of DDS for the therapeutics of infectious diseases.

Arthritis, ormalizedn by chronic joint inflammation, is increasingly prevalent due to global ageing, placing significant pressure on healthcare systems. Recent studies have identified Sirtuin 6 (Sirt6) as a promising therapeutic target for alleviating arthritis symptoms. This study investigates the therapeutic potential of Sirt6-loaded cationic liposomes in a collagen-induced arthritis (CIA) rat model. Sirt6-loaded cationic liposomes were prepared and ormalizedn using transmission electron microscopy, particle size distribution, polydispersity index (PDI), zeta potential, encapsulation efficiency, in vitro release, and stability studies. The optimal Sirt6 plasmid-to-liposome ratio was established at 1:1000. Characterisation confirmed a spherical morphology, with a particle size of 177.65 ± 2.09 nm, a PDI of 0.216 ± 0.013, and zeta potential of 21.78 ± 1.76 Mv. The liposomes exhibited superior release profiles and storage stability, thus maintaining their integrity for up to 30 days and achieving 90.77 ± 3.35% release efficiency within 24 h. In vitro, the endocytosis of Sirt6-loaded liposomes significantly increased Sirt6 protein expression in chondrocytes (p < 0.01). In vivo, treatment reduced inflammation in liver and spleen tissues and lowered pro-inflammatory cytokines associated with CIA (p < 0.01). These findings support Sirt6-loaded liposomes as a potential novel therapeutic strategy for treatment of arthritis.

Osteoporosis is a common systemic skeletal disease characterised by altered bone metabolism, decreased bone mass, deteriorated microstructure, and an increased risk of fractures. Current treatments primarily focus on inhibiting bone resorption to reduce bone loss. However, anti-resorptive agents alone cannot restore the lost bone microstructure. Therefore, developing dual-action drugs that both inhibit bone resorption and promote bone formation is a major research focus. In this study, we integrated network pharmacology and transcriptomics to screen for drugs that can be used to treat osteoporosis, and further identified compounds with potential synergistic effects in both inhibiting bone resorption and promoting osteogenesis. We found that calpeptin exhibited dual-intervention properties. Given its established anti-resorptive effect, we focused on exploring its osteogenesis-promoting mechanism. In vitro experiments demonstrated that calpeptin significantly enhanced osteogenic differentiation of BMSCs by activating the Dlx3-RUNX2 pathway. In an ovariectomy-induced osteoporotic mouse model, calpeptin treatment for 4 weeks alleviated bone loss and significantly promoted osteogenesis. This study reveals the unique mechanism by which calpeptin activates bone formation via the Dlx3-RUNX2 pathway, providing a new multi-target intervention paradigm for the development of breakthrough osteoporosis therapies.

Infertility affects millions of women worldwide, with causes ranging from ovarian dysfunction to endometrial disorders. Conventional treatments, such as hormone therapy and assisted reproductive technologies (ART), often have limited success and significant side effects. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising alternative, offering therapeutic potential through their cargo of proteins, nucleic acids, and bioactive molecules that regulate tissue repair and regeneration. This review explores the role of EVs in addressing female infertility by enhancing ovarian follicle development, improving endometrial receptivity, and mitigating inflammation or fibrosis in reproductive tissues. We summarise preclinical and clinical evidence supporting EV-based therapies, discuss key mechanisms of action, and highlight challenges in translation, including standardisation, scalability, and safety. By evaluating current advancements and future prospects, this review highlights the experimental potential of EVs as a novel, cell-free approach under investigation for restoring fertility in women.

Purpose: This study aimed to develop sustainable synthetic routes for novel enaminonitrile pyridine derivatives and evaluate a lead compound's potential as a dual-action theranostic agent for oncology, combining targeted therapy and diagnostic imaging.

Methods: Two green chemistry techniques were utilised: microwave-assisted and solvent-free mechanochemical grinding. The lead compound 7 was assessed for in vitro anticancer activity against MCF-7 cells. It was radiolabeled with iodine-131, optimising parameters like substrate amount and pH. Finally, in vivo biodistribution and tumour targeting were studied in tumour-bearing mice.

Results: The green synthesis was highly efficient. Compound 7 showed superior anticancer activity (IC₅₀ = 3.77 ± 0.43 µM) versus cisplatin. Radiolabeling achieved high radiochemical purity (95.74 ± 1.44%). Biodistribution studies confirmed excellent, selective tumour uptake (9.07% ID/g at 1 h) with sustained retention (7.91% ID/g at 24 h) and high target-to-background ratios.

Conclusions: This work successfully establishes efficient green synthesis routes. Compound 7 is a potent and selective sustainable theranostic agent, effectively merging green chemistry principles with precision oncology applications for both therapy and diagnosis.

Colorectal cancer (CRC) remains a major therapeutic challenge due to systemic toxicity and poor tumour selectivity of conventional treatments. Thymoquinone (TQ), a natural anticancer compound, faces limited clinical utility because of poor solubility and bioavailability. To overcome these challenges, a fucoidan (FC)-coated methoxy poly(ethylene glycol)-poly(lactic acid) (mPEG-PLA) nanoparticle system was developed for targeted TQ delivery. The optimised FC-coated TQ nanoparticles (∼105 nm) exhibited high encapsulation efficiency (82.3 ± 0.77%) and low polydispersity (<0.2), enabling passive tumour targeting via the enhanced permeability and retention (EPR) effect. The formulation showed sustained, pH-responsive release and enhanced cytotoxicity in HCT-116 cells (IC₅₀ = 68.97 ± 1.10 µM) compared to uncoated NPs and free TQ. Confocal microscopy confirmed efficient uptake, while Western blot analysis demonstrated a concentration-dependent increase in cleaved caspase-3 in HCT-116 and HT-29 cells, indicating apoptosis induction. In vivo, FC-coated TQ-NPs induced significant tumour regression (75.26 ± 2.24%) and prolonged median survival (49 days) in C26 tumour-bearing mice versus free TQ (22 days). Biochemical analysis showed normal hepatic (alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and renal (blood urea nitrogen (BUN), creatinine) profiles, and cardiac histology remained intact, confirming biosafety. Thus, FC-coated mPEG-PLA-TQ nanoparticles enhance efficacy and safety, offering a promising nanoplatform for targeted CRC therapy.