免疫刺激性DNA水凝胶递送药物联合治疗脑胶质瘤

Malignant gliomas are highly infiltrative, so it extremely recurrence after surgery. TMZ is an alkylating agent for the treatment of malignant glioma, the synergic therapy of TMZ and Lgb can effectively improve the killing rate for the tumor through the prevention of drug resistance. The traditional drug delivery is difficult to realize the slow-release of drug and multiple administration are needed for killing cancer cells completely. Therefore, this research constructs an immunostimulatory CpG DNA hydrogels based on the CpG nucleotide for loading TMZ and Lgb to treat of malignant gliomas after surgery. The CpG DNA hydrogels drug delivery system has the following advantages: (1) It has good biocompatibility and loading efficiency for drug; (2) It possesses good bioresponsiveness and sustained release capability; (3) the hydrogels itself possesses immunostimulation and is capable of achieving immunotherapy to malignant gliomas. This project will study the efficiency and mechanism of CpG DNA hydrogels treatment for malignant glioma in vitro and in vivo, which contributes to solve the problem of glioma recurrent after surgery, and provides the theoretical and experimental basis for the development of new techniques and methods in treatment of glioma.

恶性胶质瘤呈浸润性生长，术后极易复发。替莫唑胺（Temozolomide, TMZ）是术后临床常用化疗药物，通过联合罗米鲁曲（Lomeguatrib, Lgb）用药可有效防止耐药提高肿瘤杀伤率。传统的药物递送方式难以做到药物缓释，故而需要多次给药才能彻底杀伤癌细胞。为此，本项目基于含有免疫刺激序列的CpG核苷酸构建具有免疫刺激性的CpG DNA水凝胶来荷载TMZ和Lgb，通过化疗与免疫治疗实现术后脑胶质瘤。该水凝胶载药系统具有以下优点：（1）具有优异的生物相容性和荷载药物效率；（2）具有良好的生物刺激性响应性和缓释性；（3）水凝胶本身具有免疫刺激性，可实现免疫治疗。本项目将从体内外深入研究CpG DNA水凝胶对恶性胶质瘤的治疗效率及机理，这有助于解决脑胶质瘤术后治疗易于复发的难题，同时为开发新的治疗脑胶质瘤的技术和方法提供理论依据和实验基础。

恶性胶质瘤占颅脑肿瘤的40-50%，是最常见的颅内恶性肿瘤，呈浸润性生长，术后极易复发。替莫唑胺（Temozolomide, TMZ）是术后临床常用化疗药物，对胶质瘤显示出了良好的治疗作用。传统的药物递送方式难以做到药物缓释，故而需要多次给药才能彻底杀伤癌细胞。为此，本项目基于含有免疫刺激序列的CpG核苷酸构建具有免疫刺激性的CpG DNA水凝胶来荷载TMZ，通过化疗与免疫治疗实现术后脑胶质瘤。该水凝胶载药系统具有以下优点：（1）具有优异的生物相容性和荷载药物效率；（2）具有良好的生物刺激性响应性和缓释性；（3）水凝胶本身具有免疫刺激性，可实现免疫治疗。本项目从体内外深入研究了CpG DNA水凝胶荷载TMZ（CpG-TMZ）后对恶性胶质瘤的治疗效率及机理，发现CpG-TMZ在体外能够有效杀伤脑胶质瘤细胞株，并且能够显著抑制脑胶质瘤细胞株的侵袭与迁移，同时还能明显抑制脑胶质瘤细胞株的克隆形成能力。体内研究结果表明CpG-TMZ能够有效抑制脑胶质瘤小鼠的肿瘤生长。本项目有助于解决脑胶质瘤术后治疗易于复发的难题，同时为开发新的治疗脑胶质瘤的技术和方法提供理论依据和实验基础。