中文摘要
设计并构建具有靶向、多重响应的功能化纳米凝胶给药系统,通过靶向肿瘤组织、近红外响应、肿瘤酸性环境响应、抑制肿瘤细胞与新生血管内皮细胞的粘附、抑制新生血管生成及直接杀死肿瘤细胞等多重作用,达到抗肿瘤转移及抗肿瘤效果。选择阿霉素(DOX)为模型药物,氧化锌纳米粒(ZnO)为酸敏感纳米粒,低分子肝素(LMHP)为凝胶材料,寡聚脯氨酸片段(OP)为交联剂,LMHP-DOX-ZnO为可响应近红外光释放ROS,进而断裂OP键而解散凝胶系统的物质,制备包载LMHP-DOX-ZnO、经OP交联LMHP的靶向、多重响应的功能化纳米凝胶给药系统(LMHP-DOX-ZnO@LMHP-OP)。该给药系统可解决抗肿瘤药物在血液循环系统中泄漏的问题、LMHP单独使用具有导致出血毒副作用的问题、多重响应触发释药解决单一触发释药可控性不强的问题。该给药系统为抗肿瘤及抗肿瘤转移的研究提供了新思路,具有非常重要的科学价值。
英文摘要
A targeting and muli-stimuli responsive nanogel drug delivery system is designed to both inhibit tumor metastasis by preventing the adhesion of tumor cells to new vascular endothelial cells and restraining the formation of new blood vessels, and killing tumors directly. The nanogels would reach tumor tissues by targeting effect, response to near-infrared light (NIR) to get separated, and get dissolved in the acidic microenvironment of tumors. DOX is selected as a model drug, ZnO is an pH sensitive nanoparticle to response the low pH environment in tumors, low molecular weight heparin (LMHP) is served as a gel material and the oligomeric proline fragment (OP) is used as a linker to cross-link the nanogels to entrap LMHP-DOX-ZnO, which has the photodynamic properties to generate ROS after excited by NIR. The ROS produced by LMHP-DOX-ZnO would induce the break of OP to disrupt the nanogels. The drug delivery system we built could solve the leakage problem of anti-tumor drugs in blood circulation system, and the side effect of bleeding when LMHP is used as an anti-tumor agent. The nanogels are triggered to release drugs by multiple stimuli, which has a better control of drugs compared with single stimulus responsive delivery systems. This program also offers a new thought for researches of antineoplastic and anti-metastasis, and has a significant value for application.
