Lee Jin Gyun, Petraccione Joseph, Trese Katherine A, Hughes Alex C, Ausec Taylor R, Salzmann-Sullivan Maren, Su Lih-Jen, Kim Matthew T, Roh Sangchul, Goodwin Andrew P, Feng Frances Xiuyan, Flaig Thomas W, Shields C Wyatt
Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Ave, Boulder, CO, 80303, USA.
Division of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue 8122, Aurora, CO, 80045, USA.
Adv Mater. 2025 Jul 4:e2505231. doi: 10.1002/adma.202505231.
Bladder cancer is a leading cause of cancer-related mortality, yet current intravesical drug delivery methods often suffer from poor retention times in the bladder. Gecko feet-like nanomaterials offer the potential to overcome this challenge, however, conventional methods to fabricate high surface area nanomaterials for drug delivery involve complex and expensive manufacturing processes. In this work, a simple fluid flow templating method is reported for manufacturing soft dendritic particles (SDPs) composed of poly(lactic-co-glycolic acid) (PLGA) with a chitosan coating for enhanced adhesion to epithelial tissues via van der Waals interactions. The biodegradable SDPs encapsulate chemotherapeutic agents and are administered using an alginate hydrogel, enabling precise deposition by extrusion for sustained drug release. The results demonstrate that SDPs adhere to mouse and human cancer cells for several days. The SDPs effectively encapsulate and release several clinically utilized chemotherapeutic drugs such as gemcitabine, docetaxel, and methotrexate, exhibiting superior cancer cell killing in vitro. In murine models, gemcitabine-loaded SDPs instilled into tumor-bearing bladders elicited stronger CD45+ immune cell responses than control groups while maintaining minimal toxicity. This work presents a simple, biomimetic drug delivery platform with prolonged retention and controlled drug release, offering a versatile approach for enhancing therapeutic delivery in epithelial cancer models.
膀胱癌是癌症相关死亡的主要原因之一，然而目前的膀胱内给药方法在膀胱中的保留时间往往较短。壁虎脚状纳米材料有望克服这一挑战，然而，用于药物递送的高表面积纳米材料的传统制造方法涉及复杂且昂贵的制造工艺。在这项工作中，报道了一种简单的流体流动模板法，用于制造由聚乳酸-乙醇酸共聚物（PLGA）组成的软树枝状颗粒（SDPs），其具有壳聚糖涂层，可通过范德华相互作用增强对上上皮组织的粘附。可生物降解的SDPs包裹化疗药物，并使用藻酸盐水凝胶给药，通过挤压实现精确沉积以实现药物的持续释放。结果表明，SDPs在小鼠和人类癌细胞上粘附了数天。SDPs有效地包裹并释放了几种临床使用的化疗药物，如吉西他滨、多西他赛和甲氨蝶呤，在体外表现出优异的癌细胞杀伤能力。在小鼠模型中，将负载吉西他滨的SDPs注入荷瘤膀胱中，与对照组相比，引发了更强的CD45+免疫细胞反应，同时毒性最小。这项工作提出了一种简单的仿生药物递送平台，具有延长的保留时间和可控的药物释放，为增强上皮癌模型中的治疗递送提供了一种通用方法。
