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

Oct 17, 2019ACS applied materials & interfaces

Targeted Treatments Using Peptides That Cross Brain and Tumor Barriers for Glioma and Brain Cancer Spread

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Abstract

A novel peptide capable of penetrating the blood-brain barrier may enhance treatment for glioma and breast cancer brain metastases.

Glioma is the most common malignant tumor of the central nervous system.
The blood-brain barrier and blood-brain tumor barrier limit drug delivery to brain tumors.
Peptide-drug conjugates were developed from a newly identified peptide that can cross these barriers.
Antitumor activity was observed in glioma and breast cancer brain metastases models.
Combining the peptide-drug conjugates with temozolomide resulted in synergistic effects.

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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.

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

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