Brain-Targeted Delivery Systems for Treatment of Brain Diseases

    Brain diseases such as glioblastoma and Alzheimer's disease remain difficult to treat mainly due to the fact that most drugs are not able to penetrate the blood-brain barrier (BBB). The development of BBB-permeable nanovehicles to realize brain-targeted delivery of small molecule drugs, protein and peptide drugs, and nucleic acids might lead to breakthrough in the treatments of brain diseases including glioblastoma and Alzheimer's disease. We found that Angiopep-2 and ApoE peptide-functionalized smart polymersomes could efficiently load and deliver oncoprotein inhibitor Rigosertib, protein, siRNA and adjuvants to glioblastoma, resulting in effective treatment of orthotopic glioblastoma. We plan to further investigate the treatment efficacy of Angiopep-2 and ApoE peptide-functionalized smart polymersomes toward glioblastoma PDX models and Alzheimer's disease.


  

  

Representative Papers

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 smart 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.