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Acid-activatable Polymeric Drug Delivery Systems for Cancer Therapy
- Acta Polymerica Sinica Vol. 50, Issue 11, Pages: 1156-1166(2019)
- 作者机构：
1.中国科学院上海药物研究所 新药研究国家重点实验室 药物制剂研究中心 上海 201203
2.南通大学药学院 南通 226001
- 作者简介：
- 基金信息：
DOI：10.11777/j.issn1000-3304.2019.19133
CLC：Published：2019-11，
Published Online：16 September 2019，
Received：12 July 2019，
Revised：9 August 2019，
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Jing Gao, Wei-qi Wang, Hai-jun Yu. Acid-activatable Polymeric Drug Delivery Systems for Cancer Therapy. [J]. Acta Polymerica Sinica 50(11):1156-1166(2019)
Jing Gao, Wei-qi Wang, Hai-jun Yu. Acid-activatable Polymeric Drug Delivery Systems for Cancer Therapy. [J]. Acta Polymerica Sinica 50(11):1156-1166(2019) DOI： 10.11777/j.issn1000-3304.2019.19133.
摘要
纳米递药系统有望实现药物靶向递送增加其生物利用度、降低其毒副作用，在肿瘤治疗方面受到了广泛关注. 但是，抗肿瘤药物的体内递送是一个多步骤的复杂过程，如何有效克服肿瘤组织(肿瘤部位的特异性富集滞留、深部渗透、高效细胞摄取)及细胞内(胞内可控药物释放)的多重物理屏障是抗肿瘤纳米递药系统面临的重大挑战. 利用肿瘤组织及细胞内的微酸环境，在药物载体材料中引入酸响应化学键或功能基团，构建酸响应性纳米递药系统是实现肿瘤特异性药物递送、提高药物递送效率的有效途径. 本文系统回顾了本课题组近年来在运用酸敏感高分子载体材料设计构建智能纳米递药系统，克服药物递送的关键物理屏障，改善肿瘤治疗效果方面的研究进展，并对其转化前景进行了展望.
Abstract
The polymeric drug delivery systems (DDS) have showed promising potential for improving cancer therapy
which can lengthen the blood circulation and minimize the adverse effect of chemotherapeutics. Despite promising
the therapeutic performance of polymeric-based DDS is affected by a series of physiological barriers
including limited tumor accumulation
restricted tumor penetration
insufficient cellular uptake
and slow drug release inside the tumor cells. It has been well-investigated that there is an acidic microenvironment inside the solid tumors due to the abnormal glucose metabolism of tumor cells. Moreover
the subcellular organelles including endosome and lysosome display much lower acidic pH than that of cytosol. The extracellular and intracellular acidic microenvironments have thus been exploited as both a trigger and target for tumor-targeted drug delivery. In this review article
we summarized our recent advances in developing acid-responsive polymeric DDS by taking the advantage of the acidic microenvironment of tumor tissue and tumor cells. We particularly highlighted the acid-responsive chemical bonds and components employed for constructing the acid-activatable DDS. These acid-activatable nanovectors have been exploited for combating the physiological barriers by surface charge conversion
nanostructure dissociation
and ligand presentation. We also provided a perspective regarding of the challenges and opportunities about clinical translation of the stimuli-activatable DDS.
关键词
纳米递药系统高分子载体材料肿瘤微酸环境肿瘤物理屏障
Keywords
Nanosized drug delivery systemTumor acidic microenvironmentPolymeric nanoparticlesPhysiological barriers
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