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A dual-targeted hyaluronic acid-gold nanorod platform with triple-stimuli responsiveness for photodynamic/photothermal therapy of breast cancer
摘要： Multi-stimuli-responsive theranostic nanoplatform integrating functions of both imaging and multimodal therapeutics holds great promise for improving diagnosis and therapeutic efficacy. In this study, we reported a pH, glutathione (GSH) and hyaluronidase (HAase) triple-responsive nanoplatform for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT dual-therapy against HER2-overexpressed breast cancer. The nanoplatform was fabricated by functionalizing gold nanorods (GNRs) with hyaluronic acid (HA) bearing pendant hydrazide and thiol groups via Au-S bonds, and subsequently chemically conjugating 5-aminolevulinic acid (ALA), Cy7.5 and anti-HER2 antibody onto HA moiety for PDT, fluorescence imaging and active targeting, respectively. The resulting versatile nanoplatform GNR-HA-ALA/Cy7.5-HER2 had uniform sizes, favorable dispersibility, as well as pH, GSH and HAase triple-responsive drug release manner. In vitro studies demonstrated that HER2 and CD44 receptor-mediated dual-targeting strategy could significantly enhance the cellular uptake of GNR-HA-ALA/Cy7.5-HER2. Under near-infrared (NIR) irradiation, MCF-7 cells could efficiently generate reactive oxygen species (ROS) and heat, and be more efficiently killed by a combination of PDT and PTT as compared with individual therapy. Pharmacokinetic and biodistribution studies showed that the nanoplatform possessed a circulation half-life of 1.9 h and could be specifically delivered to tumor tissues with an accumulation ratio of 12.8%. Upon the fluorescence imaging-guided PDT/PTT treatments, the tumors were completely eliminated without obvious side effects. The results suggest that the GNR-HA-ALA/Cy7.5-HER2 hold great potential for breast cancer therapy.
关键词： Triple-responsive drug release,Hyaluronic acid,Gold nanorod,Photodynamic and photothermal dual-therapy,Targeted delivery
更新于2025-09-10 09:29:36
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Nanoparticulate photosensitizer decorated with hyaluronic acid for photodynamic/photothermal cancer targeting therapy
摘要： Aim: A photomedicine consisting of a core for photothermal therapy, a photosensitizer for photodynamic therapy, and a cancer-targeting moiety was fabricated to improve photosensitizer selectivity and antitumor efficiency. Materials & methods: Hyaluronic acid-decorated polydopamine nanoparticles with conjugated chlorin e6 (HA–PDA–Ce6) were synthesized and characterized. Cell uptake, phototoxicity, penetration, distribution and therapeutic effects were evaluated. Results: HA–PDA–Ce6 had high photoactivities for photodynamic therapy/photothermal therapy and was readily internalized via CD44-mediated endocytosis. Enhanced accumulation and deeper penetration into tumors were achieved by the diffusion molecular retention tumor targeting effect following peritumoral injection. In the combination therapy, HA–PDA–Ce6 displayed the highest tumor growth inhibition in HCT-116 tumor-bearing mice. Conclusion: HA–PDA–Ce6 is promising for targeted colorectal cancer therapy.
关键词： peritumoral injection,polydopamine nanoparticles,photothermal therapy,photodynamic therapy,hyaluronic acid,chlorin e6
更新于2025-09-09 09:28:46
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The impact of a hyaluronic acid-grafted layer on the surface properties of model silicone hydrogel contact lenses
摘要： The introduction of high oxygen transmissibility silicone hydrogel lenses ameliorated hypoxia-related complications, making them the most prescribed type of contact lens. Despite the progress made over the last two decades to improve their clinical performance, symptoms of ocular dryness and discomfort and a variety of adverse clinical events are still reported. Consequently, the rate of contact lens wear discontinuation has not been appreciably diminished by their introduction. Aiming to improve the interfacial interactions of silicone hydrogel contact lenses with the ocular surface, a biomimetic layer of the hydrophilic glycosaminoglycan hyaluronic acid (HA) (100 kDa), was covalently attached to the surface of model poly(2-hydroxyethyl methacrylate-co-3-methacryloxypropyl-tris-(trimethylsiloxy)silane) (pHEMA-co-TRIS) silicone hydrogel materials via UV-induced thiol-ene “click” chemistry. The surface structural changes after each modification step were studied by FTIR-ATR and XPS. Successful grafting of a homogenous HA layer to the surface of the model silicone hydrogels was confirmed by the consistent appearance of N (1s) and the significant decrease of the Si (2p) peaks, as determined by the low-resolution angle-resolved XPS. The HA-grafted surfaces demonstrated reduced contact angles, dehydration rate and nonspecific deposition of lysozyme and albumin, while maintaining their optical transparency (>90%). In vitro studies demonstrated that the HA-grafted pHEMA-co-TRIS materials did not show any toxicity to human corneal epithelial cells. These results suggest that surface immobilization of HA via thiol-ene “click” chemistry can be used as a promising surface treatment for silicone hydrogel contact lenses.
关键词： surface modification,dehydration,contact lenses,hyaluronic acid,MTT assay,thiol-ene chemistry,protein deposition,Silicone hydrogel
更新于2025-09-04 15:30:14