Novel bone tumor cell targeting nanosystem for chemo-photothermal therapy of malignant bone tumors

Abstract

The bone microenvironment provides a “barrier” for bone tumors to resist clinical chemoradiotherapy, implying that molecules targeting tumor cells alone cannot effectively target bone tumor cells. One restriction of using nanosystems in the treatment of bone tumors is bone tumor cell-targeting. In this study, a novel chemo-photothermal combined therapy (CPT) bone tumor cell-targeting nanosystem was designed. A bone tumor cell-targeting peptide (BTTP) was covalently attached to the surface of the nanosystem. The nanosystem was constructed by hybridization of a core Mn-Co metal-organic framework and polydopamine as the shell (TM@P). The TM@P/DOX nanosystem could be first targeted to the bone damage interface by the bone-targeting peptide octapolyaspartic acid (D8) of BTTP. Then the KCQGWI↓GQPGCK polypeptide fragment of BTTP could be cut off by matrix metalloproteinases (MMPs) secreted by bone tumors, and finally guided specifically the nanosystem into bone tumor cells by cell penetrating peptides (R8) of BTTP. Doxorubicin (DOX) was loaded onto the TM@P surface (TM@P/DOX). The nanosystem targeted bone tumor cells well in vivo and enhanced the contrast of bone tumor (MRI). Finally, the TM@P/DOX nanosystem-mediated CPT effectively inhibited bone tumor growth and osteolysis. This study provides an effective new approach for the treatment of malignant bone tumors.