具有纳米结构卷须的柔软可挤压树突状颗粒用于膀胱癌的局部粘附和药物释放。

IF 27.4 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jin Gyun Lee, Joseph Petraccione, Katherine A Trese, Alex C Hughes, Taylor R Ausec, Maren Salzmann-Sullivan, Lih-Jen Su, Matthew T Kim, Sangchul Roh, Andrew P Goodwin, Frances Xiuyan Feng, Thomas W Flaig, C Wyatt Shields
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引用次数: 0

摘要

膀胱癌是癌症相关死亡的主要原因,但目前膀胱内给药方法往往存在膀胱滞留时间短的问题。像壁虎脚一样的纳米材料提供了克服这一挑战的潜力,然而,传统的制造用于药物输送的高表面积纳米材料的方法涉及复杂和昂贵的制造过程。在这项工作中,报告了一种简单的流体流动模板方法,用于制造由聚乳酸-羟基乙酸(PLGA)和壳聚糖涂层组成的软树突状颗粒(sdp),通过范德华相互作用增强与上皮组织的粘附。可生物降解的sdp包封化疗药物,并使用海藻酸盐水凝胶给药,通过挤压实现精确沉积,以实现持续的药物释放。结果表明,sdp在小鼠和人类癌细胞上粘附数天。sdp有效封装并释放吉西他滨、多西他赛和甲氨蝶呤等几种临床使用的化疗药物,在体外表现出卓越的癌细胞杀伤能力。在小鼠模型中,将吉西他滨负载的sdp灌注到荷瘤膀胱中,引起了比对照组更强的CD45+免疫细胞反应,同时保持了最小的毒性。本研究提出了一种简单的仿生给药平台,具有延长药物保留时间和控制药物释放,为加强上皮性癌症模型的治疗递送提供了一种通用的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Soft Extrudable Dendritic Particles with Nanostructured Tendrils for Local Adhesion and Drug Release to Bladder Cancers.

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.

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来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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