A degradable triple temperature-, pH-, and redox-responsive drug system for cancer chemotherapy
A degradable triple temperature-, pH-, and redox-responsive drug system for cancer chemotherapy
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用于癌症化疗的可降解三重温度、pH 和氧化还原响应药物系统
DOI：
10.1002/jbm.a.36515
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发表时间：
2018
影响因子：
4.9
通讯作者：
Cong Hailin
中科院分区：
文献类型：
--
作者：
Yu Bing;Song Na;Hu Hao;Chen Guihuan;Shen Youqing;Cong Hailin
为了实现癌症治疗的精确治疗效果并提高药物的利用率，合成了温度、pH和氧化还原响应的药物递送系统。采用蒸馏-沉淀聚合法，将甲基丙烯酸（MAA）、聚（N-异丙基丙烯酰胺）（PNIPAM）、甲基丙烯酸2-羟乙酯（HEMA）和含二硫键的交联剂N，N′-双（丙烯酰基）胱胺（BACy）进行聚合。阿霉素（DOX）是一种抗癌药物，可以有效地负载到松散的纳米颗粒（NP）中。制备的药物载体在血液循环过程中保持稳定，当载体在肿瘤组织中积累时，MMA的pH响应和PNIPAM的温度响应使载体体积收缩，有利于载体向肿瘤组织中扩散。当药物被肿瘤细胞内吞后，其所含的二硫键可被谷胱甘肽（GSH）切割，导致纳米粒的分解，从而释放出全部药物。在三种触发因素的作用下，三重刺激响应型药物传递载体可以实现肿瘤蓄积、肿瘤穿透和药物控释。因此，制备的多响应NP是开发新型药物递送系统的理想药物载体。© 2018 Wiley Periodicals，Inc. J Biomed Mater Res Part A：106A：3203-3210，2018.
In order to achieve a precise therapeutic effect of cancer treatment and improve the utilization of drugs, a temperature‐, pH‐, and redox‐responsive drug delivery system were synthesized. Methacrylic acid (MAA), poly(N‐isopropylacrylamide) (PNIPAM), 2‐hydroxyethylmethacrylate (HEMA), andN,N′‐bis(acryloyl)cystamine (BACy), a disulfide bond contained cross‐linker, were polymerized by a distillation‐precipitation polymerization. Doxorubicin (DOX), an anti‐cancer drug, can be loaded into the loose nanoparticle (NP) effectively. The prepared drug delivery remains stable during blood circulation and, when the vectors accumulated at tumor tissues, the pH‐response of MMA and temperature‐response of PNIPAM makes volume shrinkage of vectors which benefit the diffusion of vectors into tumor tissues. After being endocytosed into tumor cell, the disulfide bond that contained in the drug delivery can be cleaved by glutathione (GSH), causing the decomposition of NPs, and then release all of the drug. Under the influence of three trigger factors, the triple stimuli‐responsive drug delivery vectors can realize tumor accumulation, tumor penetration and controlled drug release. Thus, the prepared multi‐responsive NP is ideal drug carriers for developing novel drug delivery systems. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3203–3210, 2018.