Advances in lysosomal escape mechanisms for gynecological cancer nano-therapeutics.

Journal of pharmaceutical analysis Pub Date : 2024-12-01 Epub Date: 2024-10-15 DOI:10.1016/j.jpha.2024.101119
Heng Wei, Yingying Hao, Jin Zhang, Yue Qi, Chong Feng, Chen Zhang
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Abstract

Gynecological cancers present significant treatment challenges due to drug resistance and adverse side effects. This review explores advancements in lysosomal escape mechanisms, essential for enhancing nano-therapeutic efficacy. Strategies such as pH-sensitive linkers and membrane fusion are examined, showcasing their potential to improve therapeutic outcomes in ovarian, cervical, and uterine cancers. We delve into novel materials and strategies developed to bypass the lysosomal barrier, including pH-sensitive linkers, fusogenic lipids, and nanoparticles (NPs) engineered for endosomal disruption. Mechanisms such as the proton sponge effect, where NPs induce osmotic swelling and rupture of the lysosomal membrane, and membrane fusion, which facilitates the release of therapeutic agents directly into the cytoplasm, are explored in detail. These innovations not only promise to improve therapeutic outcomes but also minimize side effects, marking a significant step forward in the treatment of ovarian, cervical, and uterine cancers. By providing a comprehensive analysis of current advancements and their implications for clinical applications, this review sheds light on the potential of lysosomal escape strategies to revolutionize gynecological cancer treatment, setting the stage for future research and development in this vital area.

妇科肿瘤纳米治疗中溶酶体逃逸机制的研究进展。
由于耐药和不良副作用,妇科癌症的治疗面临重大挑战。本文综述了对提高纳米治疗效果至关重要的溶酶体逃逸机制的研究进展。研究了诸如ph敏感连接子和膜融合等策略,展示了它们改善卵巢癌、宫颈癌和子宫癌治疗结果的潜力。我们深入研究了绕过溶酶体屏障的新材料和策略,包括ph敏感连接物、促聚变脂质和用于内体破坏的纳米颗粒(NPs)。详细探讨了诸如质子海绵效应(NPs诱导溶酶体膜渗透肿胀和破裂)和膜融合(促进治疗剂直接释放到细胞质中)等机制。这些创新不仅有望改善治疗效果,而且还将副作用降至最低,标志着卵巢癌、宫颈癌和子宫癌治疗向前迈出了重要一步。通过全面分析目前的进展及其对临床应用的影响,本综述揭示了溶酶体逃逸策略在妇科癌症治疗中的潜力,为这一重要领域的未来研究和发展奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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