Advanced Therapeutics最新文献

Plasmonic gold nanorattles (AuNRTs), with their distinctive core@void@shell structure, have emerged as a next-generation platform for cancer nanotheranostics. Their hollow and porous morphology not only red-shifts localized surface plasmon resonance into the biologically transparent near infrared-I (NIR-I) and near infrared-II (NIR-II) windows, but also enhances photothermal conversion efficiency, electromagnetic hot-spot generation, and drug-loading capacity. These multifunctional features allow AuNRTs to integrate high-contrast bioimaging modalities with plasmonic photothermal therapy and synergistic chemo-photothermal treatment within a single nanostructure. Recent advances highlight diverse shape- and composition-controlled designs as well as multimetallic yolk–shell hybrids (Pd, Pt, Cu_2−xS), which demonstrate good performance in in vitro and in vivo tumor models. Despite these advances, challenges including antibody conjugation efficiency, toxicity from surfactant, limited penetration depth of NIR irradiation, and scalability barriers continue to impede clinical translation. Emerging solutions such as synthesis strategies with biocompatible polymers, site-specific bioconjugation, and simplified “one-for-all” multifunctional platforms hold promise for overcoming these limitations. This review critically summarizes progress in design, properties, and applications of plasmonic Au-NRTs for cancer theranostics, while outlining translational challenges and future opportunities. By bridging diagnostics and therapeutics into a single tunable platform, AuNRTs represent a powerful step toward precision therapy and image-guided cancer management.

Skin cancer remains a significant global health challenge, with chemotherapy often limited by suboptimal therapeutic outcomes. One of the major barriers to effective treatment is the limited penetration of chemotherapeutic agents into the tumor microenvironment, which restricts drug availability at the target site. Staphylococcus aureus infections contribute to tumor-promoting microenvironments, chemoresistance, clustering, and invasion of melanoma cells, highlighting the need for therapeutic approaches targeting both bacterial infections and cancer. This study introduces a dual-action nanosystem, gold-coated algosomes (ALG/Au), synthesized from Spirulina-derived lipids, rich in polyunsaturated fatty acids, for combined photodynamic (PDT) and photothermal therapy (PTT) against bacteria and cancer cells. ALG/Au achieved a temperature rise up to 50°C under laser irradiation, facilitating reactive oxygen species (ROS) generation and bacterial elimination via lipid peroxidation-mediated cell membrane damage. The system exhibited >95% inhibition of S. aureus biofilm formation, strong anti-hemolytic activity, and excellent hemocompatibility with minimal cytotoxicity in L929 and NIH3T3 fibroblast cell lines. Additionally, ALG/Au demonstrated significant melanoma cell death in the B16 3D spheroid and S. aureus in vitro co-culture model, underscoring its potential for targeting cancer and tumor-residing bacteria. These findings highlight the effectiveness of ALG/Au nanoparticles in simultaneously targeting bacterial infections and cancer cells through synergistic PDT and PTT mechanisms.

MicroRNAs (miRNAs), are essential mediators of gene expression, playing a complex dual role in the regulation of carcinogenesis and the progression of malignancies. Notably, the differential expression of miR-145 between normal and malignant contexts, observed in both cell line models and clinical samples, highlights its potential role as a tumor-suppressor. Nevertheless, challenges in the clinical translation of miR-145 cancer therapy, including exogenous miR-145 delivery, endogenous miR-145 expression, and its off-target effects, remain inadequately addressed. This review aims to provide a comprehensive synthesis of the functional roles of miR-145 in breast cancer progression, with particular emphasis on its regulatory effects on cell proliferation, invasion, angiogenesis, chemoresistance, and epithelial–mesenchymal transition (EMT). We further explore its upstream modulators and downstream targets, and highlight the mechanistic diversity underlying its context-specific functions. Finally, we discuss the current advances and limitations of miR-145 delivery platforms, focusing on preclinical strategies for improving specificity and therapeutic efficacy. By consolidating the dualistic roles and therapeutic implications of miR-145, this review provides insights to guide future translational efforts and precision miRNA-based therapy development.

The mechanisms driving hepatocellular carcinoma (HCC) progression are governed by a complex interplay among epithelial-mesenchymal transition (EMT), inflammation, angiogenesis, and impaired immune response. This study explored the efficacy of a pH-sensitive silibinin-loaded nanogel (NSB) combined with low-dose radiation (LDR) in modulating these mechanisms. Male Wistar rats (180–220 g) are divided into seven groups (n = 6): control, LDR (0.25 Gy/week), NSB (25 mg/kg), HCC, HCC+LDR, HCC+NSB, and HCC+LDR+NSB. Combined treatment with LDR and NSB significantly upregulated CDH1 expression while decreasing the transcription levels of TWIST1, ROCK1, TNF-α, RELA, HIF1A, CXCL12, CXCR4, VEGF, and CD274, compared to the untreated HCC group and the corresponding monotherapy groups (P < 0.05). Additionally, immunological analyses revealed a notable decline in serum interleukin (IL)-6 levels and a concurrent increase in IL-12, accompanied by enhanced CD8 expression relative to the untreated HCC group and monotherapy groups (P < 0.05). Moreover, LDR+NSB regimen effectively enhanced hepatic function indices, mitigated oxidative damage driven by diethylnitrosamine (DEN), and augmented endogenous antioxidant activities, compared to the untreated HCC and single-treatment groups (P < 0.05). In conclusion, these results suggest that the synergistic integration of NSB with LDR represents a promising multi-targeted approach for attenuating key drivers of HCC progression while augmenting adaptive anti-tumor immune responses.

USP49 regulates various cellular processes as a deubiquitinase during the development of cancer. However, the roles of USP49 in ovarian cancer (OC) remain obscure. Here, it is shown that USP49 is amplified in OC, which is associated with elevated mRNA expression. Although USP49 inhibition has no significant influence on the proliferation of OC cells, USP49 overexpression promotes drug resistance to cisplatin treatment in Tp53-WT OC cells. Mechanistically, USP49 decreases ubiquitination of γH2AX and enhances DNA damage repair, impairing cell apoptosis of OC cells in response to cisplatin treatment. In addition, co-expression of USP49 and ATAD5 is identified in OC, and inhibition of USP49 and ATAD5 increases drug sensitivity to cisplatin in Tp53-WT OC cells. In conclusion, these findings demonstrate the role of USP49 on cisplatin resistance and suggest that repressing USP49 and ATAD5 can be a potential therapeutic strategy for cisplatin-resistant ovarian cancer.

Treatment of Candida albicans infections is becoming increasingly challenging due to rising antifungal resistance. Fungi-responsive drug delivery systems have the potential to effectively treat these infections while reducing toxicity and resistance. Here, a hydrogel platform is developed that is responsive to C. albicans secreted aspartic proteases (Saps) released during different stages of infection. Peptides derived from host antimicrobial peptides, hypothesized to be cleaved by multiple Sap isoenzymes, are incorporated into the poly(ethylene glycol)-based hydrogels as crosslinkers using thiol-maleimide chemistry. Only hydrogels containing Saps-cleavable peptides degrade in the presence of C. albicans. The C. albicans-responsive hydrogels exhibit degradation-dependent release of a model nanoparticle cargo. Incubation in C. albicans Saps knockouts demonstrates an important influence of several Saps in enabling hydrogel degradation, dominated by Sap1-3. In an ex vivo porcine burn infection model, amphotericin B-containing liposomes are encapsulated in the hydrogels to assess antifungal efficacy. The responsive hydrogels undergo complete degradation on the infected burn wound in two days, and enable a 7-log reduction in fungal burden, while non-responsive hydrogels behave similar to untreated controls. Hydrogel degradation products also maintain fibroblast viability. This C. albicans-responsive hydrogel drug delivery system is a promising approach for future treatment of localized C. albicans infections.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation, joint destruction, and oxidative stress. Despite advances in treatments, RA remains incurable, with current therapies often linked to adverse effects. This study investigated the anti-arthritic potential of diosmetin encapsulated within solid lipid nanoparticles (D-SL-NPs), designed to enhance its bioavailability and therapeutic efficacy. D-SL-NPs, prepared via a modified hot plate encapsulation method, achieved 92.5% entrapment efficiency, a particle size of 7 nm, and a zeta potential of −16 mV. Significant in vitro anti-inflammatory effects are observed with the D-SL-NPs-III, including membrane stabilization (81%), protein denaturation inhibition (92%), and enhanced in vivo activities of SOD (52 U/mg), CAT (53 U/mg), and GSH (6.4 µg/mg). Moreover, D-SL-NPs-III modulated cytokine expression by suppressing TNF-α (0.17), IL-1β (0.18), MMP-13 (0.25), COX-1 (0.28), and COX-2 (0.19), while upregulating IL-10 (0.7) and IL-4 (0.93). Histopathological analysis confirmed restored joint integrity, while pharmacokinetic studies revealed a prolonged half-life (T½ = 24 h) and improved bioavailability. These findings suggest that D-SL-NPs offer a safe and effective therapeutic strategy for autoimmune arthritis. This is the first study to demonstrate their efficacy in an autoimmune model, highlighting translational potential and the need for further clinical investigation.