DNA self-assembly nanoflower reverse P-glycoprotein mediated drug resistance in chronic myelogenous leukemia therapy

Pengxuan Zhao; Yeteng Zhong; Pengcheng Pan; Shasha Zhang; Yu Tian; Jun Zhang; Guohui Yi; Zhendong Zhao; Tiantian Wu

doi:10.3389/fbioe.2023.1265199

DNA self-assembly nanoflower reverse P-glycoprotein mediated drug resistance in chronic myelogenous leukemia therapy

Front Bioeng Biotechnol. 2023 Aug 21:11:1265199. doi: 10.3389/fbioe.2023.1265199. eCollection 2023.

Authors

Pengxuan Zhao^#¹, Yeteng Zhong^#², Pengcheng Pan^#¹, Shasha Zhang^{3

4}, Yu Tian^{5

6}, Jun Zhang⁷, Guohui Yi⁴, Zhendong Zhao⁵, Tiantian Wu¹

Affiliations

¹ Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hainan Medical University, Haikou, China.
² Department of Clinical Laboratory, The Second Affiliated Hospital, Hainan Medical University, Haikou, China.
³ Wuhan Wuchang Hospital, Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China.
⁴ Public Research Center Hainan, Hainan Medical University, Haikou, China.
⁵ Analytical and Testing Center of Hainan University, Hainan University, Haikou, China.
⁶ Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, China.
⁷ Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

^# Contributed equally.

Abstract

Introduction: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder caused by the BCR-ABL chimeric tyrosine kinase. Vincristine (VCR) is widely used in leukemia therapy but is hindered by multidrug resistance (MDR). Methods: We prepared DNA nanoflower via self-assembly for the delivery of VCR and P-glycoprotein small interfering RNA (P-gp siRNA). Results and Discussion: The as-prepared nanoflower had a floriform shape with high loading efficiency of VCR (80%). Furthermore, the nanoflower could deliver VCR and P-gp siRNA into MDR CML cells and induce potent cytotoxicity both in vitro and in vivo, thus overcoming MDR of CML. Overall, this nanoflower is a promising tool for resistant CML therapy.

Keywords: DNA self-assembly; chronic myelogenous leukemia; drug delivery; drug resistance; rolling circle amplification.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by the National Natural Science Foundation of China (82202532 and 82102080), China Postdoctoral Science Foundation (2022M711528).