Bioinspired Multivalent Peptide Nanotubes for Sialic Acid Targeting and Imaging-Guided Treatment of Metastatic Melanoma.

Abstract

Tumor metastasis is considered a major cause of cancer-related human mortalities. However, it still remains a formidable challenge in clinics. Herein, a bioinspired multivalent nanoplatform for the highly effective treatment of the metastatic melanoma is reported. The versatile nanoplatform is designed by integrating indocyanine green and a chemotherapeutic drug (7-ethyl-10-hydroxycamptothecin) into phenylboronic acid (PBA)-functionalized peptide nanotubes (termed as I/S-PPNTs). I/S-PPNTs precisely target tumor cells through multivalent interaction between PBA and overexpressed sialic acid on the tumor surface in order to achieve imaging-guided combination therapy. It is demonstrated that I/S-PPNTs are efficiently internalized by the B16-F10 melanoma cells in vitro in a PBA grafting density-dependent manner. It is further shown that I/S-PPNTs specifically accumulate and deeply penetrate into both the subcutaneous and lung metastatic B16-F10 melanoma tumors. More importantly, I/S-PPNT-mediated combination chemo- and photodynamic therapy efficiently eradicates tumor and suppresses the lung metastasis of B16-F10 melanoma in an immunocompetent C57BL/6 mouse model. The results highlight the promising potential of the multivalent peptide nanotubes for active tumor targeting and imaging-guided cancer therapy.