细胞核靶向蛋白质药物纳米递送系统的构建、挑战及优化策略
Construction, Challenges and Optimization Strategies of Nuclear-Targeted Nanodelivery Systems for Protein Drugs
摘要
癌症是全球重大公共卫生问题，传统肿瘤治疗存在靶向性差、毒副作用显著等局限，亚细胞器精准靶向成为肿瘤治疗的重要发展方向。蛋白质药物因作用机制明确、生物相容性好，是替代传统化疗的理想选择，但面临细胞膜穿透难、溶酶体降解、核靶向效率低等递送瓶颈。纳米载体为蛋白递送提供了新思路，但传统载体存在制备条件苛刻、核靶向不足等缺陷，细胞穿透肽、环糊精与无铜点击化学等材料虽各具优势，但其协同构建多功能递送系统仍待探索。本文系统综述细胞核靶向蛋白递送的研究进展、递送瓶颈、纳米载体应用及关键材料优化策略，梳理亚细胞器精准治疗的研究脉络，为开发高效、安全、广谱适配的蛋白质药物细胞核靶向递送系统提供理论依据与创新思路。
Abstract
Cancer is a major global public health concern. Traditional tumor therapies are limited by poor targeting and significant side effects, so precise subcellular targeted therapy has become an important developmental direction for tumor treatment. Protein drugs are ideal alternatives to conventional chemotherapy due to their clear mechanism of action and good biocompatibility, yet they face delivery bottlenecks such as difficulty penetrating cell membranes, lysosomal degradation, and low nuclear-targeting efficiency. Nanocarriers provide new ideas for protein delivery, but conventional nanocarriers suffer from harsh preparation conditions and insufficient nuclear targeting. Although cell-penetrating peptides, cyclodextrins, copper-free click chemistry and other materials have respective advantages, their synergistic use in constructing multifunctional delivery systems remains to be explored. This paper systematically reviews the research progress of nuclear-targeted protein delivery, delivery bottlenecks, application status of nanocarriers, and optimization strategies of key materials. It sorts out the research context of precise subcellular therapy, and provides theoretical basis and innovative ideas for the development of efficient, safe and broadly applicable nuclear-targeted delivery systems for protein drugs.关键词
细胞核靶向/蛋白质药物递送/纳米递送系统/细胞穿透肽/环糊精Key words
Nuclear-targeting/Protein drug delivery/Nanodelivery systems/Cell-penetrating peptides/Cyclodextrin引用本文复制引用
黄森荣,冯旭利.细胞核靶向蛋白质药物纳米递送系统的构建、挑战及优化策略[EB/OL].(2026-04-14)[2026-04-16].http://www.paper.edu.cn/releasepaper/content/202604-120.学科分类
医学研究方法/肿瘤学
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