Enhancing cytotoxicity of daunorubicin on drug-resistant leukaemia cells with microparticle-mediated drug delivery system

Abstract

Multidrug resistance is considered as a major obstacle for effective tumour chemotherapy. With the ability to deliver drugs into tumour cells, microparticles may act as a drug delivery vehicle to overcome drug resistance. In the present study, we developed an approach employing daunorubicin-loaded microparticles to surmount the drug resistance in leukaemia. The microparticles, derived from the drug-sensitive cells K562 and the drug-resistant cells K562/ADR, composed of cellular material, can effectively package drugs using intracellular and extracellular drug-loading method, respectively. The results demonstrated that the microparticles significantly improved the drug anti-tumour effect, which was influenced by the preparation methods and the source of donor cells. We further confirmed that the uptake of microparticles is mediated by an energy-driven endocytic process and mainly associated with clathrin-independent endocytosis and macropinocytosis. These results indicated that the microparticle could serve as a promising drug vehicle for the treatment of drug-resistant leukaemia.

Keywords:

• Microparticles
• drug resistance
• leukaemia
• daunorubicin
• drug delivery system

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 81473168] and the Key Research and Development Projects of Sichuan Department of Science and Technology [grant number 2019YFS0328].