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妇科癌症纳米治疗的溶酶体逃逸机制研究进展

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

作者信息

Wei Heng, Hao Yingying, Zhang Jin, Qi Yue, Feng Chong, Zhang Chen

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 117004, China.

出版信息

J Pharm Anal. 2024 Dec;14(12):101119. doi: 10.1016/j.jpha.2024.101119. Epub 2024 Oct 15.

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.

摘要

由于耐药性和不良副作用,妇科癌症带来了重大的治疗挑战。本综述探讨了溶酶体逃逸机制的进展,这对于提高纳米治疗效果至关重要。研究了诸如pH敏感连接子和膜融合等策略,展示了它们在改善卵巢癌、宫颈癌和子宫癌治疗结果方面的潜力。我们深入研究了为绕过溶酶体屏障而开发的新型材料和策略,包括pH敏感连接子、促融合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(其中NPs诱导溶酶体膜的渗透肿胀和破裂)和膜融合(其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结果,还能将副作用降至最低,标志着卵巢癌、宫颈癌和子宫癌治疗向前迈出了重要一步。通过对当前进展及其对临床应用的影响进行全面分析,本综述揭示了溶酶体逃逸策略在彻底改变妇科癌症治疗方面的潜力,为这一重要领域的未来研究和开发奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa2/11732538/c027ad123ea3/ga1.jpg

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