Enzyme-Triggered Morphological Transition of Peptide Nanostructures for Tumor-Targeted Drug Delivery and Enhanced Cancer Therapy

The use of smart drug carriers to realize cancer-targeted drug delivery is a promising method to improve the efficiency of chemotherapy and reduce its side effects. A surfactant-like peptide, Nap-FFGPLGLARKRK, was elaborately designed for cancer-targeted drug delivery based on an enzyme-triggered morphological transition of the self-assembled nanostructures. The peptide has three functional motifs: the aromatic motif of Nap-FF- to promote peptide self-assembly, the enzyme-cleavable segment of -GPLGLA- to introduce enzyme sensitivity, and the positively charged -RKRK- segment to balance the molecular amphiphilicity as well as to facilitate interaction with cell membranes. The peptide self-assembles into long fibrils with hydrophobic inner cores, which can encapsulate a high amount of anticancer drug doxorubicin (DOX). By having enzyme responsibility, these fibrils can be degraded into thinner ones by the cancer-overexpressed matrix metalloproteinase-7 (MMP7) at tumor sites and precipitate out to give sustained release of DOX, resulting in cancer targeted drug delivery and selective cancer killing. In vivo antitumor experiments with mice confirm the high efficiency of such enzyme-responsive peptidic drug carriers in successfully suppressing the tumor growth and metastasis while greatly reducing the side effects. The study demonstrates the feasibility of using enzyme-sensitive peptide nanostructures for efficient and targeted drug delivery, which have great potential in biomedical cancer treatment.