电场响应药物输运复合功能材料及抗肿瘤靶向治疗研究

Effective and safe targeted delivery and controlled-release carrier is one of the key factors in tumor therapy. It has attracted extensive critical attention to smart controlled-release and targeted drug delivery system to improve chemotherapy outcome with tumor precision therapy. Smart controlled-release and targeted drug delivery functional materials are important biomedical functional materials. Electric field is a safe signal source that can be applied without contact in vitro. The project will study and create new electric-field-responsive drug delivery functional materials to load antitumor drug by using electric field as signal source and inorganic mesoporous materials as carriers, targeted delivery and electric-field-controlled release antitumor drug to tumor cells by synergistic action of functional molecules. (1) Multifunctional hollow mesoporous silica delivery system will be designed and assembled to meet the aim of targeting therapy tumor by electric-field-responsive drug delivery functional materials. (2) Electric-field-responsive materials will be designed and synthesized, and their electric-field-responsive mechanism will be researched to solve the problem of localization, timing and quantitative release of chemotherapy drugs. (3) Biological safety evaluation model for electric-field-responsive drug delivery system will be established to elucidate the mode and rule of chemotherapy drugs targeting and electric-field controlled release. Finally, get applicable electric-field-responsive drug delivery functional materials, providing the scientific foundation for the clinical application of the precise treatment of tumor.

高效和安全的靶向输运控释载体是肿瘤治疗的关键因素之一，针对化疗的毒副作用以及肿瘤细胞的多重耐药性问题，智能控释靶向药物输运功能载体实现精准治疗肿瘤，是生物医用功能材料领域的一个重要课题。电场是一种可体外无接触施加的安全信号源，本项目拟以电场为信号源，以无机介孔材料为载体，设计合成电场响应药物输运功能材料，通过靶向分子与载体材料协同作用，实现药物的靶向输运和电场控释。（1）针对电场响应药物输运功能材料靶向治疗肿瘤的目标，进行多功能介孔二氧化硅输运体系的功能化设计、组装和运行机制研究（2）研究电场响应性物质的设计、合成、响应机制，解决药物输运的定位、定时、定量释放问题。（3）建立电场响应药物靶向输运体系生物安全性评价模型，阐明药物靶向和电场控释方式和规律，建立电场响应药物输运体系靶向治疗肿瘤的方法。获得满足体内应用要求的电场响应药物输运复合功能材料，对精准治疗肿瘤的临床实际应用奠定科学基础。

高效和安全的靶向输运控释载体是肿瘤治疗的关键因素之一，针对化疗的毒副作用以及肿瘤细胞的多重耐药性问题，智能控释靶向药物输运功能载体实现精准治疗肿瘤，是生物医用功能材料领域的一个重要课题。电场是一种可体外无接触施加的安全信号源，本项目以电场为信号源，以无机和有机介孔材料为载体，设计合成电场响应药物输运功能材料，通过靶向分子与载体材料协同作用，实现药物的靶向输运和电场控释。（1）研究并制备介孔二氧化硅/聚硝基苯基甲基丙烯酰胺‐叶酸靶向药物输运体系,在介孔材料中接枝功能分子能够有效地将药物包埋在电场响应型靶向给药纳米系统中，并通过电场响应来控制药物的释放，并降低药物的非特异性泄漏，增强了肿瘤抑制作用。（2）研究了中空介孔有机硅/高铁酸盐‐原卟啉‐月桂酸纳米输运体系，该体系中氧气产生、谷胱甘肽的原位耗尽和活性氧的释放三种功能协同作用，抑制肿瘤生长。（3）研究并制备中空介孔二氧化硅/过氧化钙‐四氧化三铁‐葡萄糖氧化酶/壳聚糖‐羧甲基纤维素输运体系，电场刺激使负载的客体更加快速的发生反应，从而产生更多的自由基，而当客体被完全释放后载体恢复到中空介孔结构，对其外加超声作用，载体因介孔和中空结构发生超声空化作用，可以进一步生成自由基，达到更强的杀伤肿瘤细胞的作用。在经过电场和超声刺激后，可以对肿瘤组织有很强的抑制作用和杀伤作用。此外，还进行了系列电场控释多重响应纳米药物的肿瘤治疗及其机制研究，拓展了电场响应输运材料的临床应用范围。