Tian Kun, Jia Xu, Zhao Xubo, Liu Peng
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
Mol Pharm. 2017 Mar 6;14(3):799-807. doi: 10.1021/acs.molpharmaceut.6b01051. Epub 2017 Feb 23.
Novel strategy has been developed for fabricating the biocompatible reduction and pH dual-responsive core cross-linked (CCL) micelles as drug delivery system (DDS) for the controlled anticancer drug delivery, via the atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBA) with N,N'-bis(acryloyl)cystamine (BACy) as cross-linker and a multifunctional amphiphilic linear-hyperbranched copolymer as macroinitiator, which was synthesized via the self-condensing vinyl copolymerization (SCVCP) of tBA and p-chloromethylstyrene (CMS) with a poly(ethylene glycol) (PEG) based initiator (mPEG-Br). The hydrolyzed core cross-linked (HCCL) micelles were obtained as DDS for doxorubicin (DOX) by hydrolysis the tBA units into acrylic acid (AA) ones. The in vitro release performance showed that higher GSH concentration and/or lower pH value would lead to a faster and more efficient DOX release, meaning their reduction and pH dual-responsiveness. Therefore, the proposed HCCL micelles are expected to be potential anticancer drug-carriers for tumor microenvironment responsive controlled delivery.
已经开发出一种新策略，用于制备生物相容性还原和pH双响应的核交联（CCL）胶束作为药物递送系统（DDS），用于控制抗癌药物递送。该策略通过丙烯酸叔丁酯（tBA）与N，N'-双（丙烯酰基）胱胺（BACy）作为交联剂进行原子转移自由基聚合（ATRP），并以多功能两亲性线性-超支化共聚物作为大分子引发剂，该大分子引发剂是通过tBA和对氯甲基苯乙烯（CMS）与基于聚乙二醇（PEG）的引发剂（mPEG-Br）的自缩合乙烯基共聚合（SCVCP）合成的。通过将tBA单元水解成丙烯酸（AA）单元，获得了用于阿霉素（DOX）的水解核交联（HCCL）胶束作为DDS。体外释放性能表明，较高的谷胱甘肽浓度和/或较低的pH值会导致更快、更有效的DOX释放，这意味着它们具有还原和pH双响应性。因此，所提出的HCCL胶束有望成为用于肿瘤微环境响应性控制递送的潜在抗癌药物载体。
