脑靶向递送系统与重大脑疾病治疗

    脑相关疾病包括脑神经痛、脑胶质瘤和阿尔兹海默症等依然是难治之症,迄今尚无好的治疗方法,其中的一个重要原因是绝大多数药物难以穿过血脑屏障(BBB)。研制可穿透BBB的载体系统,实现小分子药物、蛋白药物、多肽药物和核酸药物等的脑靶向递送,可望在脑神经痛、脑胶质瘤和阿尔兹海默症等重大脑疾病的治疗上取得突破。我们发现Angiopep-2ApoE等多肽修饰的智能聚合物囊泡可高效装载小分子抑制剂Rigosertib、蛋白药物、siRNA、免疫佐剂等,穿透BBB并靶向递送到脑胶质瘤,实现原位脑胶质瘤的高效治疗,延长荷瘤鼠的存活期。我们将通过脑胶质瘤PDX模型、脑神经痛模型和阿尔兹海默症模型等进一步研究不同脑靶向药物的治疗效果


代表性论文

1)    H.Z. Qin, Y. Jiang, J. Zhang, C. Deng*, and Z.Y. Zhong*, Oncoprotein Inhibitor Rigosertib Loaded in ApoE-Targeted Smart Polymersomes Reveals a High Safety and Potency against Human Glioblastoma in Mice, Mol. Pharmaceutics 2019, 16, 3711-3719.

2)    Y.Q. Zhu, Y. Jiang, F.H. Meng, C. Deng, R. Cheng, J. Zhang*, J. Feijen*, and Z.Y. Zhong*, Highly efficacious and specific anti-glioma chemotherapy by **art tandem nanomicelles co-functionalized with brain tumor-targeting and cell-penetrating peptides, J. Control. Release 2018, 278, 1-8.

3)    Y. Jiang, W.J. Yang, J. Zhang*, F.H. Meng, and Z.Y. Zhong*, Protein Toxin Chaperoned by LRP-1 Targeted Virus-Mimicking Vesicles Induces High-Efficiency Glioblastoma Therapy In Vivo, Adv. Mater. 2018, 30, 1800316.

4)    Y. Jiang, J. Zhang*, F.H. Meng, and Z.Y. Zhong*, Apolipoprotein E Peptide-Directed Chimeric Polymersomes Mediate an Ultrahigh-Efficiency Targeted Protein Therapy for Glioblastoma, ACS Nano 2018, 12, 11070-11079.

5)    Y.Q. Zhu, J. Zhang, F.H. Meng, C. Deng, R. Cheng, J. Feijen*, and Z.Y. Zhong*, cRGD/TAT dual-ligand reversibly crosslinked micelles loaded with docetaxel penetrate deeply into tumor tissue and show high antitumor efficacy in vivo, ACS Appl. Mater. Interfaces 2017, 9, 35651-35663.