Co-delivery of doxorubicin-dihydroartemisinin prodrug/TEPP-46 nano-liposomes for improving antitumor and decreasing cardiotoxicity in B16-F10 tumor-bearing mice

  • Colloids Surf B Biointerfaces. 2024 May 26:241:113992. doi: 10.1016/j.colsurfb.2024.113992.
Qiuyue Jin  1 ,  Xiaohui Zhou  1 ,  Xiaomin Niu  1 ,  Canqi Ping  1 ,  Xiaozhou Dong  1 ,  Danyu Duan  1 ,  Rongrong Wang  1 ,  Yi Chen  1 ,  Fei Pan  1 ,  Fan Yang  1 ,  Xihua Yang  2 ,  Guoshun Zhang  1 ,  Ruili Wang  1 ,  Shuqiu Zhang  3 ,  Guolian Ren  4
Affiliations
  • 1. School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China.
  • 2. Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
  • 3. School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: [email protected].
  • 4. School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: [email protected].
PMID: 38833960 DOI: 10.1016/j.colsurfb.2024.113992
Abstract

In order to reduce the cardiotoxicity of doxorubicin (DOX) and improve its antitumor effect, dihydroartemisinin (DHA) and DOX prodrug (DOX-S-DHA) synthesized via a single sulfur bond was used with TEPP-46 to prepare nano-liposomes (DOX-S-DHA@TEPP-46 Lips). In which, TEPP-46 was expected to exert p53 bidirectional regulation to promote the synergistic antitumor effect of DOX and DHA while reducing cardiotoxicity. DOX-S-DHA@TEPP-46 Lips exhibited uniform particle size, good stability, and excellent redox-responsive activity. DOX-S-DHA@TEPP-46 Lips could significantly inhibit the proliferation of tumor cells, but had less cytotoxicity on normal cells. The presence of TEPP-46 increased the content of p53 protein, which further induced tumor cell Apoptosis. DOX-S-DHA@TEPP-46 Lips had satisfactory long circulation to enhance the antitumor efficacy and reversed the cardiotoxicity of DOX in B16-F10 tumor-bearing mice. In conclusion, DOX-S-DHA@TEPP-46 Lips provides a new insight on creating sophisticated redox-sensitive nano-liposomes for Cancer therapy as well as the decreased cardiotoxicity of DOX.

Keywords
Antitumor; Dihydroartemisinin; Doxorubicin; Nano-liposome; TEPP-46.
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