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A blood-brain barrier and blood-brain tumor barrier penetrating peptide derived targeted therapeutics for glioma and malignant tumor brain metastases.

Research paper by Long L Chen, Dan D Zeng, Nuo N Xu, Chengpeng C Li, Wenyuan W Zhang, Xin-Jie XJ Zhu, Yan Y Gao, Peng R PR Chen, Jian J Lin

Indexed on: 18 Oct '19Published on: 17 Oct '19Published in: ACS Applied Materials & Interfaces



Abstract

Glioma is the most common malignant tumor of central nervous system (CNS). Therapeutic efficacy of glioma treatments is greatly limited by the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which restrict the passage of most drugs into brain and tumors. Developing drug delivery systems that cross the BBB and BBTB will aid in treatment of glioma and malignant brain metastases. One emerging solution is to identify peptide vectors that penetrate BBB/BBTB. Herein, a novel BBB/BBTB-penetrating peptide was identified from phage-displayed peptide library. Peptide-drug conjugates (PDCs) were derived and applied to treat glioma and breast cancer brain metastases. Anti-tumor activity was achieved in both tumor models with synergistic effects when combined with the currently used chemotherapy drug temozolomide. The peptide reported herein can serve as a universal vector for shuttling compounds across the BBB; therefore, it may have wide applications for treating brain tumors as well as other CNS diseases.