Xu Long, Zhao Mingying, Yang Yidi, Liang Yan, Sun Changzhen, Gao Wenxia, Li Sai, He Bin, Pu Yuji
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
J Mater Chem B. 2017 Dec 14;5(46):9157-9164. doi: 10.1039/c7tb02359f. Epub 2017 Nov 16.
Low molecular weight gels (LMWGs) have significant advantages in drug delivery such as high drug loading capacity, in situ delivery of drug to the lesion site, sustaining drug release with excellent bioavailability, and minimized side effects. Here, we synthesized a reactive oxygen species (ROS)-responsive gelator to prepare an injectable gel. An anticancer drug, doxorubicin hydrochloride (DOX), and a photosensitizer, Zn(ii) phthalocyanine tetrasulfonic acid (ZnPCS), were loaded into the gel for combined chemo-photodynamic therapy. The ROS-responsive gelator was characterized by proton nuclear magnetic resonance (H NMR) and the morphology of gels was investigated by scanning electron microscopy (SEM). The rheological properties and destruction-recovery capability of both blank and drug-loaded gels were studied. The cytotoxicity of LMWGs against 3T3 fibroblasts and 4T1 breast cancer cells was tested. The in vitro drug release of both drugs was studied and the in vivo anticancer activities of DOX-ZnPCS-coloaded LMWGs were investigated in tumor-bearing mice. The results revealed that the injectable ROS-responsive DOX-ZnPCS-coloaded LMWGs exhibited excellent anti-tumor efficacy by a synergistic therapy.
低分子量凝胶(LMWGs)在药物递送方面具有显著优势,如高载药量、药物原位递送至病变部位、持续释药且生物利用度优异以及副作用最小化。在此,我们合成了一种活性氧(ROS)响应性凝胶因子以制备可注射凝胶。将一种抗癌药物盐酸多柔比星(DOX)和一种光敏剂四磺酸锌酞菁(ZnPCS)负载到凝胶中用于联合化学-光动力疗法。通过质子核磁共振(H NMR)对ROS响应性凝胶因子进行了表征,并通过扫描电子显微镜(SEM)研究了凝胶的形态。研究了空白凝胶和载药凝胶的流变学性质及破坏-恢复能力。测试了LMWGs对3T3成纤维细胞和4T1乳腺癌细胞的细胞毒性。研究了两种药物的体外释药情况,并在荷瘤小鼠中研究了共负载DOX-ZnPCS的LMWGs的体内抗癌活性。结果表明,可注射的ROS响应性共负载DOX-ZnPCS的LMWGs通过协同疗法表现出优异的抗肿瘤疗效。