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.
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.
作者
高晶
王伟奇
于海军
Jing Gao;Wei-qi Wang;Hai-jun Yu(State Key Laboratory of Drug Research&Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203;School of Pharmacy,Nantong University,Nantong 226001)
出处
《高分子学报》
SCIE
CAS
CSCD
北大核心
2019年第11期1158-1168,共11页
Acta Polymerica Sinica
基金
国家自然科学基金(基金号31671024,31622025,51873228)资助项目
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
Nanosized drug delivery system
Tumor acidic microenvironment
Polymeric nanoparticles
Physiological barriers
作者简介
通讯联系人:于海军,E-mail:hjyu@simm.ac.cn。
