Journal of Drug Targeting最新文献

Prostate cancer is one of the most common malignancies globally, with chemotherapy remaining a cornerstone treatment for advanced and metastatic cases. However, traditional chemotherapy is limited by poor targeting, low bioavailability, and systemic toxicity, necessitating the development of precise chemotherapy strategies. Nanotechnology has emerged as a promising platform to address these limitations by enabling targeted drug delivery. This review systematically synthesises advancements in nanotechnology-based drug delivery systems and their targeting strategies, emphasising their application in prostate cancer therapy. Active targeting approaches leverage cell membrane receptors, such as prostate-specific membrane antigen (PSMA), folate receptor, transferrin receptor, and CD44, as biomarkers. Corresponding ligands, including PSMA ligands, folate derivatives, transferrin, hyaluronic acid, chondroitin sulphate, and DUP-1, are used to modify nanocarriers, conferring precise targeting capabilities to loaded chemotherapeutics. Additionally, bioinspired strategies employing cell membrane encapsulation and magnetic field-guided delivery are discussed. Meanwhile, the review comprehensively summarises the research advancements of nanodelivery systems in combination therapy involving chemotherapy and radiotherapy, photodynamic therapy, immunotherapy, and other modalities. Through a categorised analysis of the developments and challenges of these nanotechnologies, this review intends to furnish references and new orientations for the research and application of precise chemotherapy in prostate cancer.

Background: Knee osteoarthritis (KOA) is a prevalent chronic inflammatory joint disorder in clinical practice, characterized by pathological dysfunction of the "gut-joint axis". Although platelet-rich plasma (PRP) has demonstrated therapeutic efficacy in improving KOA symptoms, its precise underlying mechanisms remain to be fully elucidated.

Method: In this study, 16S rRNA sequencing was initially employed to analyze fecal samples from conventionally raised rats and pseudo-germ-free (pGF) rats established by our research group, enabling the identification of significantly altered microbial taxa, which were selected as target microbiota for subsequent investigations. A KOA rat model was induced via intra-articular injection of monosodium iodoacetate (MIA). Following model establishment, the target microbiota were administered orally via gavage, while PRP was delivered through intra-articular injection as a combined intervention. Therapeutic outcomes were assessed using gait analysis, joint swelling measurements, and micro-CT scanning. Joint pathological changes were evaluated through hematoxylin-eosin (HE) staining, safranin O-fast green staining, and standardized scoring systems for osteoarthritis and synovitis. Immunohistochemical staining was performed to detect the expression levels of α-smooth muscle actin (α-SMA) and type II collagen (Collagen II) in articular cartilage. Additionally, fecal samples from nine clinical patients with KOA were collected to examine gut microbiota composition and monitor its dynamic changes before and after PRP treatment.

Result: Ligilactobacillus murinus (L. murinus) was identified as the predominant differentially abundant microorganism following PRP intervention in pGF rats. In the KOA rat model, both individual supplementation with L. murinus and PRP treatment significantly improved gait performance and bone-related parameters, alleviated pathological damage to articular cartilage, reduced proteoglycan loss in the cartilage matrix, decreased osteoarthritis and synovitis scores, and upregulated the expression of α-SMA and Collagen II in articular cartilage. Notably, the combination of L. murinus and PRP exerted a more pronounced therapeutic effect. In clinical patients, PRP intervention improved knee function, but L. murinus was not a dominant species and its abundance further declined post-treatment, suggesting that PRP efficacy in humans may involve distinct or functionally redundant microbial taxa.

Conclusion: The combination of L. murinus and PRP may exert enhanced therapeutic effects in ameliorating KOA through modulation of the gut microbiota, with their co-administration showing greater efficacy than either treatment alone.

Cancer therapy-induced cardiotoxicity represents a serious clinical complication driven by oxidative injury, topoisomerase IIβ-mediated DNA damage, endoplasmic reticulum (ER) stress, mitochondrial dysfunction and sustained inflammatory signalling. These pathogenic processes can lead to a range of adverse outcomes, including myocarditis, vascular and valvular alterations, myocardial fibrosis, electrophysiological remodelling and related cardiac abnormalities. A growing body of experimental evidence indicates that nanocarriers can markedly reduce unintended cardiac exposure to cytotoxic agents. These systems exploit the enhanced permeability and retention (EPR) effect in the tumour microenvironment while lowering free drug concentrations in the myocardium. Progress in targeting strategies, spanning surface-functionalised ligands and antibodies to stimuli-responsive nanoparticles, further constrains off-target distribution and enables spatially controlled drug release at the tumour site. In parallel, nanoparticles co-loaded with cardioprotective agents, including antioxidants, Top2β inhibitors, small molecules and selected natural products, demonstrate additive benefits by intercepting central mediators of cardiomyocyte injury. Such dual co-delivery platforms may also augment antitumour efficacy. Nanocarriers incorporating these cardioprotective agents may similarly attenuate radiotherapy-induced cardiotoxicity. This review critically evaluates these multifaceted nanomedicine strategies and outlines a comprehensive roadmap for harnessing nanoparticle technologies to prevent and mitigate cardiotoxicity associated with cancer therapy.

Isoxsuprine (ISX) is a blood flow-improving beta-adrenergic agonist that provides cardiotoxicity protection. However, the limited effectiveness of ISX can be attributed to a short half-life and low bioavailability. The focus of this study was to create ISX-loaded transbilosomes (ILT), improving sustainability, permeability, bioavailability, safety, and ISX therapeutic efficacy as a safe option for managing cardiotoxicity. Different ILT formulations were developed using design expert software. Additionally, a rat model of cardiotoxicity was used to conduct an in vivo study to assess its bioavailability, safety, and efficacy. An optimized ILT formulation was identified, consisting of 275 mg phospholipid, 20 mg cholesterol, 25 mg Span 60, and 20 mg sodium deoxycholate. This formulation achieved a release rate of 29.22%, a permeation rate of 95.66%, and resulted in a 3.55-fold increase in bioavailability. Compared to the disease group, the optimized ILT significantly reduced mortality and levels of troponin-1, LDH, CK-MB, and MDA by 23.89%, 99.03%, 94.77%, 96.77%, and 96.57%, respectively. Furthermore, it enhanced the GSH, SOD, and CAT by 3.69-fold, 3.54-fold, and 3.57-fold, respectively. These findings suggest that nasal ILT could be an innovative avenue to consider for treating cardiotoxicity.

Doxorubicin (DOX), an anthracycline antibiotic, stands as one of the most potent and clinically ubiquitous chemotherapeutic agents for cancer treatment. Despite advances in clinical supportive care, strategies to prevent DOX-induced toxicity remain inadequate-with cardiotoxicity being a particularly devastating complication that can progress to heart failure. To address this unmet need, we engineered a novel core-shell biomimetic nanoparticle (NP) camouflaged with erythrocyte membranes, tailored for the targeted delivery of DOX to treat liver cancer while mitigating DOX-induced cardiotoxicity. This erythrocyte membrane-camouflaged biomimetic NP system exhibits an average diameter of 262.4 nm-an optimal size for prolonged systemic circulation-and possesses exceptional biocompatibility, coupled with enhanced responsiveness to the acidic tumor microenvironment. These synergistic features collectively augment the anti-tumor efficacy of DOX against hepatocellular carcinoma (HCC). Our findings highlight that the erythrocyte membrane-camouflaged NP serves as a promising biomimetic nanocarrier: it enables efficient delivery of chemotherapeutics to tumor sites while attenuating their off-target side effects (e.g., DOX-induced cardiotoxicity). This work thus provides a valuable strategy for improving the therapeutic index of anthracycline-based cancer treatments.

Immunometabolism is central to chronic inflammatory diseases, with metabolic reprogramming including dysregulated glycolysis, mitochondrial dysfunction, and excessive ROS production driving pathology in conditions like IBD, rheumatoid arthritis, and psoriasis. Although metabolic regulators hold therapeutic promise, their efficacy is limited by poor site-specific delivery and bioavailability. Nanotechnology-based platforms (e.g., liposomes, polymeric nanoparticles, nanoemulsions, metal nanoparticles) address these barriers by enhancing bioavailability and forming a protein corona that modulates nanoparticle uptake by macrophages and T cells, directly influencing metabolic fate. Advanced organelle-targeting strategies such as mitochondria-directed liposomes and lysosome-responsive polymers enable precise metabolic rescue by restoring mitochondrial respiration or modulating nutrient-sensing pathways. By targeting key metabolic nodes including HIF-1α, mTOR, and AMPK, nanocarriers actively shift immune cells from pro-inflammatory glycolysis toward anti-inflammatory oxidative phosphorylation, minimizing toxicity and restoring immune homeostasis. Thus, nanocarriers function not as passive delivery vehicles but as sophisticated immunometabolism modulators. Despite progress, a comprehensive review bridging nanomaterial design and metabolic intervention remains lacking. This review addresses that gap by highlighting nanoscale phenomena such as stimulus-responsive release, membrane perturbation, and organelle-specific targeting.

Research on wound-healing agents is a growing area in modern biomedical sciences, and oxidative stress plays a significant role in the challenges of chronic wound healing. These challenges include dry dressings that lack functionality and cause increased pain by adhering to wounds. Hydrogels are widely utilised for wound healing because they mimic the native extracellular matrix (ECM) and help maintain a moist environment. In silico docking studies revealed that lutein forms strong and stable interactions with proteins involved in ECM degradation, inflammation and oxidative stress. The optimised hydrogel formulations demonstrated excellent physicochemical stability and improved topical delivery of the drug. In vitro and ex vivo studies confirmed superior skin permeation and sustained release of lutein from the fermented hydrogel compared with controls. In vivo experiments using F2 formulation (0.5% lutein) on diabetic rat models demonstrated rapid wound contraction, achieving 92.1% closure by day 9 and complete healing by day 11, with minimal scarring and enhanced tissue regeneration. Histopathological analysis supported these results, revealing dense granulation tissue, minimal inflammatory infiltration and notable dermal remodelling in the treatment group. These findings suggest that lutein-loaded hydrogels are promising biotherapeutic options for the effective management of diabetic wounds.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for nearly 75-85% of total cases. As per recent global cancer estimates, over 900,000 new cases and more than 800,000 deaths occur annually, reflecting its high incidence and poor survival outcome. Despite advancements in surgical, systemic, and immunotherapeutic approaches, treatment efficacy for advanced HCC remains limited due to tumour hypoxia, recurrence, drug resistance, and off-target toxicities. Sonodynamic therapy (SDT), a non-invasive, ultrasound-activated therapeutic modality, has emerged as a promising strategy owing to its deep tissue penetration, minimal invasiveness, and controllable ROS-mediated cytotoxicity. Nanotechnology-enabled SDT significantly enhances sonosensitizer stability, tumour-specific delivery, and multifunctional therapeutic effects. Recent innovations include the development of organic, inorganic, and hybrid nano-sonosensitizers, along with synergistic combinations such as gene therapy, immunotherapy, chemotherapy, ferroptosis, pyroptosis, cuproptosis, and disulfidptosis induction. Moreover, image-guided SDT using ultrasound, MRI, and fluorescence platforms allows precise localisation and real-time therapeutic monitoring. Despite these promising advancements, clinical translation faces challenges involving biosafety, biodegradability, targeting specificity, and lack of standardised SDT protocols. This review comprehensively highlights SDT mechanisms, nanoplatform classifications, recent therapeutic strategies, safety concerns, and future research directions to facilitate effective and translational SDT-based liver cancer therapy.

Chemoresistance, often associated with multidrug resistance (MDR), is a significant challenge in cancer treatment. P-glycoprotein (P-gp) is overexpressed in various MDR cancers and is a drug efflux transporter of chemotherapeutics. Astragaloside II (AST-II) and astragaloside IV (AST-IV) are bioactive compounds extracted from the plant species Astragalus membranaceus. This study investigated the MDR reverse ability in cancer and the underlying mechanisms of AST-II and AST-IV. Results demonstrated that both compounds inhibited P-gp efflux function by suppressing ATPase activity and non-competitively interacting with P-gp substrates rhodamine123 and doxorubicin. The MDR reversal effects of AST-II and AST-IV were observed in MDR KB-vin cells by suppressing ABCB1 mRNA expression, inducing G2/M cell-cycle arrest as well as enhancing apoptosis. Both compounds exhibited synergistic effects with paclitaxel in inhibiting tumour growth in vivo. These findings suggested that AST- II and AST-IV are potential candidates for development as synergistic agents in MDR cancer treatments.