Blood–Brain Barrier- and Blood–Brain Tumor Barrier-Penetrating Peptide-Derived Targeted Therapeutics for Glioma and Malignant Tumor Brain Metastases

Glioma is the most common malignant tumor of the central nervous system (CNS). Therapeutic efficacy of glioma treatment is greatly limited by the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB), which restrict the passage of most drugs into the brain and tumors. Developing drug delivery systems that cross the BBB and BBTB will aid in the treatment of glioma and malignant brain metastases. One emerging solution is to identify peptide vectors that penetrate the BBB/BBTB. Herein, a novel BBB/BBTB-penetrating peptide was identified from the phage-displayed peptide library. Peptide–drug conjugates (PDCs) were derived and applied to treat glioma and breast cancer brain metastases. Antitumor 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 and other CNS diseases.