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基于紫杉烷前药的纳米药物用于癌症治疗。

Taxanes prodrug-based nanomedicines for cancer therapy.

机构信息

Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China; School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China.

出版信息

J Control Release. 2022 Aug;348:672-691. doi: 10.1016/j.jconrel.2022.06.004. Epub 2022 Jun 21.

Abstract

Malignant tumor remains a huge threat to human health and chemotherapy still occupies an important place in clinical tumor treatment. As a kind of potent antimitotic agent, taxanes act as the first-line broad-spectrum cancer drug in clinical use. However, disadvantages such as prominent hydrophobicity, severe off-target toxicity or multidrug resistance lead to unsatisfactory therapeutic effects, which restricts its wider usage. The efficient delivery of taxanes is still quite a challenge despite the rapid developments in biomaterials and nanotechnology. Great progress has been made in prodrug-based nanomedicines (PNS) for cancer therapy due to their outstanding advantages such as high drug loading efficiency, low carrier induced immunogenicity, tumor stimuli-responsive drug release, combinational therapy and so on. Based on the numerous developments in this filed, this review summarized latest updates of taxanes prodrugs-based nanomedicines (TPNS), focusing on polymer-drug conjugate-based nanoformulations, small molecular prodrug-based self-assembled nanoparticles and prodrug-encapsulated nanosystems. In addition, the new trends of tumor stimuli-responsive TPNS were also discussed. Moreover, the future challenges of TPNS for clinical translation were highlighted. We here expect this review will inspire researchers to explore more practical taxanes prodrug-based nano-delivery systems for clinical use.

摘要

恶性肿瘤仍然是对人类健康的巨大威胁,化疗在临床肿瘤治疗中仍然占有重要地位。作为一种有效的抗有丝分裂剂,紫杉烷类药物作为临床应用的一线广谱抗癌药物。然而,其显著的疏水性、严重的脱靶毒性或多药耐药性等缺点导致治疗效果不理想,限制了其更广泛的应用。尽管生物材料和纳米技术发展迅速,但紫杉烷类药物的有效传递仍然是一个相当大的挑战。基于前药的纳米药物(PNS)在癌症治疗方面取得了很大的进展,因为它们具有载药效率高、载体诱导免疫原性低、肿瘤刺激响应性药物释放、联合治疗等突出优点。基于这一领域的众多发展,本综述总结了基于紫杉烷前药的纳米药物(TPNS)的最新进展,重点介绍了聚合物-药物偶联物纳米制剂、小分子前药自组装纳米颗粒和前药包封纳米系统。此外,还讨论了肿瘤刺激响应性 TPNS 的新趋势。此外,还强调了 TPNS 临床转化的未来挑战。我们希望这篇综述能激发研究人员探索更多实用的基于紫杉烷前药的纳米递药系统,用于临床应用。

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