刺激响应型聚合物前药

Stimuli-Responsive and Polymeric Prodrugs

前药(prodrug)是一类经过生物体内转化后才具有药理作用的化合物。与传统纳米药物输送系统相比具有载药率确定、稳定性高、爆释现象小等优点。但是,前药本身也面临着可控性,特异性释药不足而引起效果不佳等问题。因此,能够靶向病灶部位并能够针对病灶部位进行特异性释药的刺激敏感型前药受到广泛研究。本文以国内外学者及本课题组的研究成果为基础,以肿瘤部位特殊的生理环境为背景,综述了近年来pH敏感、温敏、氧化还原敏感、酶敏感等生物刺激响应型抗肿瘤聚合物前药的研究进展。

Prodrugs represent the compounds that can convert to the bioactive drugs under in vitro or in vivo environment after administration, which have received intensive and extensive attention in the past decades. Among them, several of clinical successes have been achieved, disclosing the promising future of prodrugs. As compared with the conventional nanoscaled drug delivery system, prodrug provides the merits of the high and constant drug efficiency, high stability in blood circulation and low burst release. Nonetheless, critical challenges remain in the development of prodrugs aiming at clinical benefit, mainly including the inability of controlled and targeted drug release. Prodrugs that can selectively release the carried drug specific to microenvironment of lesion site emerges as a powerful strategy to address the above issues. These prodrugs are structurally polymeric and the mechanism of the design is generally based on the physical （pH, temperature） or biological （enzyme, glutathione concentration） stimulus. Herein, we present an overview of the recent work on stimuli-responsive anticancer polymeric prodrugs, including pH-sensitive, redox sensitive and enzyme digestion, based on the domestic and international research progress. In addition, recent advances and future directions in the development of stimuli-responsive and polymeric prodrugs are also included.