雷公藤甲素功能化纳米递药系统用于抗肿瘤的研究进展

Research progress on triptolide functionalized nanoparticulate drug delivery systems for tumor treatment

目前中医药用于抗肿瘤的优势日益凸显,雷公藤甲素呈现出广谱、高效的抗肿瘤活性,基于纳米载体的雷公藤甲素给药体系更是具有提高药物水溶性、改善药动学行为等优点,但容易对机体产生不可忽视的毒副作用。由于肿瘤血管异质性和聚乙二醇化困境,纳米递药系统从给药到发挥作用需克服多重生理及病理屏障。传统的雷公藤甲素纳米递药系统仅依靠实体瘤高渗透长滞留效应,难以实现纳米药物在肿瘤组织的主动蓄积、靶部位的特异性药物释放等,限制其抗肿瘤应用和临床转化。新型功能化纳米递药系统在传统纳米制剂的基础上,进一步提高纳米药物在肿瘤部位的富集、穿透和药物控释等性能,在增强药效、降低毒副作用、提高生物利用度等方面具有重要的意义。该文对近年来雷公藤甲素的新型功能化纳米递药系统,包括肿瘤主动靶向、肿瘤微环境响应、聚合物-药物偶联、多药共载联合4个方面用于抗肿瘤的研究进展进行了总结和分析,以期为雷公藤甲素等中药有效成分抗肿瘤的深入研究和临床应用提供思路。

Nowadays,the advantages of traditional Chinese medicine(TCM)for treatment of tumors are increasingly prominent.Triptolide shows wide-spectrum and highly effective anti-tumor activity.Moreover,nano-carrier-based triptolide drug delivery system is more powerful in improving water solubility and pharmacokinetic behavior of the drug,but it is easy to cause toxic and side effects that should not be neglected on human body.Because of tumor vascular heterogeneity and PEGylation dilemma,nanoparticulate drug delivery systems need to overcome multiple physiological and pathological barriers from drug administration to functioning.It is difficult for traditional triptolide nanoparticulate drug delivery systems to achieve active accumulation of nano-drug in tumor tissues and specific drug release in tumor target site solely relying on enhanced permeability and retention effect of solid tumor,limiting their application and clinical transformation in treatment of tumors.Based on the traditional nano-preparation system,the new functionalized nano-drug delivery system further enhances the nano-drug enrichment,penetration and controlled release at the tumor sites,which is of great significance in improving bioavailability,anti-tumor efficacy and reducing the side effects of drugs.In this paper,we summarized and analyzed the researches on new triptolide functionalized nano-drug delivery system from four perspectives,including tumor active targeting,tumor microenvironment response,polymer-drug conjugates,and multidrug co-delivery for tumor treatment,expecting to provide ideas for in-depth research and clinical application of triptolide and some other active anti-tumor TCM ingredients.