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

We design a novel bone tumor cell targeting nanosystem for chemo-photothermal combined therapy. The nanosystem is constructed by hybridization of Mn-Co metal organic frameworks as core and polydopamine as shell. Its surface is loaded with doxorubicin and modified bone tumor cell targeting peptide. The nanosystem can break through the "barrier" of bone microenvironment and target bone tumor cells efficiently. [Display omitted] • One-step method to prepare Metal organic framework@polydopamine nanoparticles. • Design and synthesis of bone tumor targeting peptide modified nanosystem. • Nanosystem targets bone tumor cells by break through the bone microenvironment. • Nanosystem can treat bone tumors by chemo-photothermal combined therapy. • Nanosystem can inhibit bone tumors growth and the accompanying osteolysis. 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 (D 8) 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 (R 8) 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. [ABSTRACT FROM AUTHOR]