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用于癌症治疗的金属纳米颗粒:DNA损伤的精准靶向

Metal nanoparticles for cancer therapy: Precision targeting of DNA damage.

作者信息

Chen Qian, Fang Chunyan, Xia Fan, Wang Qiyue, Li Fangyuan, Ling Daishun

机构信息

Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

Acta Pharm Sin B. 2024 Mar;14(3):1132-1149. doi: 10.1016/j.apsb.2023.08.031. Epub 2023 Sep 3.

Abstract

Cancer, a complex and heterogeneous disease, arises from genomic instability. Currently, DNA damage-based cancer treatments, including radiotherapy and chemotherapy, are employed in clinical practice. However, the efficacy and safety of these therapies are constrained by various factors, limiting their ability to meet current clinical demands. Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy. Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms. In this review, we delve into the design principles and optimization strategies of metal nanoparticles. We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles. These encompass targeted drug delivery, inhibition of DNA repair mechanisms, induction of cell death, and the cascading immune response. Moreover, we explore the pivotal role of physicochemical factors such as nanoparticle size, stimuli-responsiveness, and surface modification in shaping metal nanoparticle platforms. Finally, we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy, paving the way for novel treatment paradigms.

摘要

癌症是一种复杂的异质性疾病,由基因组不稳定引发。目前,基于DNA损伤的癌症治疗方法,包括放疗和化疗,已应用于临床实践。然而,这些疗法的疗效和安全性受到多种因素的限制,使其难以满足当前的临床需求。金属纳米颗粒为增强基于DNA损伤的癌症治疗的各个关键方面提供了有前景的途径。其可定制的物理化学性质能够开发出靶向性和个性化的治疗平台。在这篇综述中,我们深入探讨了金属纳米颗粒的设计原则和优化策略。我们揭示了基于DNA损伤疗法的局限性,同时强调了金属纳米颗粒带来的多种可能策略。这些策略包括靶向药物递送、抑制DNA修复机制、诱导细胞死亡以及级联免疫反应。此外,我们探讨了诸如纳米颗粒大小、刺激响应性和表面修饰等物理化学因素在塑造金属纳米颗粒平台中的关键作用。最后,我们阐述了金属纳米颗粒在推进基于DNA损伤的癌症治疗方面面临的挑战和未来方向,为新的治疗模式铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e814/10934341/be2e122ede0a/ga1.jpg

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