4.6 Article

Selenium-doped calcium phosphate biomineral reverses multidrug resistance to enhance bone tumor chemotherapy

出版社

ELSEVIER
DOI: 10.1016/j.nano.2020.102322

关键词

Calcium phosphate; Osteosarcoma; Multidrug resistance; Biomineral; Drug delivery

资金

  1. National Natural Science Foundation of China [81572630, 81872174, 31771081]
  2. Science and Technology Commission of Shanghai Municipality [18ZR1445100, 19XD1402900, 19JC1414300]
  3. S&T Innovation 2025 Major Special Programme of Ningbo [2018B10040]

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The study demonstrates the potential of selenium-doped calcium phosphate biomineral (Se-CaP) in reversing multidrug resistance in bone tumors, with high biocompatibility, biodegradability, and pH-sensitive drug release properties. Se-CaP can serve as an effective drug carrier and induce apoptosis in osteosarcoma by generating intracellular reactive oxygen species.
The construction of a functional drug delivery system to reverse the multidrug resistance (MDR) of bone tumors in cases of failed chemotherapy remains a challenge. Herein, we demonstrate a selenium-doped calcium phosphate (Se-CaP) biomineral with high biocompatibility, biodegradability and pH-sensitive drug release properties. Se-CaP may not only serve as an effective drug-carrier to enhance the uptake of doxorubicin (DOX), but may also synchronously induce caspases-mediated apoptosis of osteosarcoma by generating intracellular reactive oxygen species (ROS). Furthermore, in vitro and in vivo studies obviously demonstrate that Se-CaP can reverse the MDR of osteosarcoma by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (ABCB1 and ABCC1). Finally, DOX-loaded Se-CaP can significantly inhibit DOX-resistant MG63 (MG63/DXR) tumor growth in nude mice. Considering its biomimetic chemical properties, the Se-CaP biomineral, with the multiple functions mentioned above, could be a promising candidate for treating bone tumors with MDR characteristics. (c) 2020 Elsevier Inc. All rights reserved.

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