A study on reversing multidrug resistance of MCF-7/ADR cells by inhibiting doxorubicin efflux with a fluorinated nanomedicine delivery system
- VernacularTitle:一种氟化纳米给药系统通过抑制阿霉素外排逆转MCF-7/ADR细胞耐药性的研究
- Author:
Huai-Tao SUN
1
,
2
;
Yin-Hua LIN
;
Yu-Rong SUN
;
Qiao CHEN
;
Shuo CHEN
;
Yu CAO
Author Information
- Keywords: fluorinated nano; drug delivery; P-glyco-protein; in vitro activity; drug efflux; multidrug resist-ance
- From: Chinese Pharmacological Bulletin 2024;40(6):1124-1130
- CountryChina
- Language:Chinese
- Abstract: Aim To achieve efficient loading of doxo-rubicin(doxorubicin,dox)by synthesizing fluorinated nanomaterials,and to study the mechanism of nano-medicine against multidrug resistance in tumors.Methods The physicochemical properties of nano dox(nano-doxorubicin)at different degrees of fluorination(PF4 and PF8)were evaluated through various physi-cochemical parameters,and nano dox formulations were screened out with superior fluorination.The mechanism of nano dox in overcoming multidrug resist-ance in tumors was investigated and in vitro anti-tumor activity was studied through research on cytotoxicity,cellular uptake,apoptosis,and resistance against the P-glycoprotein(P-glycoprotein,P-gp)efflux pump.Results By examining various physicochemical indi-cators,PF8 exhibited superior nano performance in loading doxorubicin compared to PF4.Cytotoxicity ex-periments demonstrated that the IC50 value of nano dox was only 1/40 of free dox,indicating excellent in vitro activity of nano dox in overcoming resistance and inhib-iting cell proliferation.Cell uptake and apoptosis stud-ies indicated that nano dox could effectively enhance the uptake of doxorubicin in MCF-7/ADR cells and successfully enter the cell nucleus,ultimately leading to apoptosis-induced anticancer activity.Studies on drug efflux mediated by P-glycoprotein indicated that nano dox could rapidly enter MCF-7/ADR cells through an efficient cellular uptake pathway,effective-ly bypassing the P-glycoprotein efflux pump.This dual action resulted in increased drug uptake within resistant cells and a reduction in efflux,demonstrating the po-tential of nano doxorubicin to overcome drug resist-ance.Conclusions The design of fluorinated nano dox effectively circumvents the efflux of drug molecules by P-glycoprotein,enhancing drug uptake within re-sistant tumor cells and reducing efflux.This results in an effective strategy in combating multidrug resistance in tumors.
