Journal
CHEMICAL ENGINEERING JOURNAL
Volume 446, Issue -, Pages -Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2022.136905
Keywords
Bone tumor cell-targeting; Nanosystem; Chemo-photothermal therapy; Malignant bone tumors; Metal-organic framework
Categories
Funding
- National Natural Science Foundation of China [82072396, 81901867]
- Shanghai Sailing Program [19YF1427300]
- China Postdoctoral Science Foundation [2019M651533, BX20190215]
- Program of Shanghai Academic/Technology Research Leader [19XD1434500, 21DZ2294600]
- Science and Technology Commission of Shanghai Municipality [21DZ2294600, 21490711700]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2019-I2M-5-037]
- Double Hundred Plan [20191819]
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The bone microenvironment poses a challenge to the treatment of bone tumors. This study presents a novel nanosystem that targets bone tumor cells and effectively inhibits tumor growth and osteolysis. The nanosystem is constructed by covalently attaching a bone tumor cell-targeting peptide to a core-shell structure, allowing for specific targeting and enhanced contrast.
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 chemophotothermal 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 (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.
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