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Objective: To study the anti-tumor effect of different proportions of elacridar (ELC) and doxorubicin (DOX), and determine the best combination ratio. Preparing a new type of acid-sensitive nanoparticles co-loaded with ELC and DOX using poly (benzyl malate) (PBM) as a carrier. Methods: PBM was prepared from L-aspartic acid by lactone ring opening method, then PEG was linked with acid sensitive hydrazone bond (Hz). The block polymer PBM-Hz-PEG was obtained and characterized by IR and 1H NMR. The nano micelles were prepared by dynamic dialysis. The particle size, polydispersity index (PDI), critical micelle concentration (CMC), drug loading capacity (DL) and entrapment efficiency (EE) of nano micelles were determined. Dynamic dialysis method was used to simulate the drug release performance in vitro for the drug loaded nano micelles. The cytotoxicity of the drug loaded nano micelles was evaluated by triple negative breast cancer MDA-MB-231 cell line in vitro. Results: ① ELC can enhance the sensitivity of DOX. They have the strongest antitumor effect when the molar ratio of ELC and DOX is 1:3. ② The results of IR and 1H NMR showed that the block copolymer PBM-Hz-PEG was successfully synthesized. ③ The particle size of the blank micelles was 69.67 依11.55 nm, the PDI was 0.245依0.026, and the CMC value was 3.9 滋g mL-1. The particle size of drug loaded nano micelles was slightly larger, ranging from 96.92 nm to 113.47 nm. The drug loading of ELC and DOX was consistent with the feed ratio. ④ The drug release rate curves and cytotoxicity tests in vitro of drug loaded micelles at pH 7.4 and pH 6.0 confirmed that the drug loaded micelles had good acid sensitivity. Conclusion: The combination of ELC and DOX has strong antitumor effect, and the PBM is an excellent carrier for both. The PBM-Hz-PEG nanomicelles have high drug loading rate, and their unique acid sensitivity can effectively reduce the toxicity of drugs on normal tissues and significantly increase the release of tumor tissues, which is expected to become a new intelligent drug delivery platform. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of microrna-221/222 (miR-221/222) on DOX resistance of breast cancer MDA-MB-231/doxorubicin (DOX) cells. Methods: miR-221/222 inhibitor (miR-221/222 inhibitor) was transfected into MDA-MB-231/DOX cells by liposome method, the blank control group and the negative control group were set up meanwhile. The transfection efficiency and expression level of miR-221/222 in MDA-MB-231 cell line and cell line MDA-MB-231/DOX cell line was detected by real time fluorescent quantitative PCR (qRT-PCR); the change of drug sensitivity of MDA-MB-231/DOX cells to dox after 48 hours of transfection was detected by CCK-8 tests; the apoptosis rate of MDA-MB-231/DOX cells was detected by flow cytometry (FCM); the upregulation of pro-apoptotic protein p53 up regulates apoptosis (PUMA), bcl-2 protein modifying factor (BMF) and cyclin kinase inhibitor p27 (p27kip1) in MDA-MB-231/DOX cells were detected by Western blotting (WB).Results: The expression level of miR-221/222 in MDA-MB-231/DOX cells was higher than that in MDA-MB-231 cells (P<0.05), the expression level of miR-221/222 in miR-221/222 inhibitor transfected by MDA-MB-231/DOX cells was lower than that in the blank control group and the negative control group (P<0.05) after 96 hours of treatment; compared with the blank control group, the expression level of miR-221/222 inhibitor transfected by MDA-MB-231/DOX cells was lower than that in the blank control group (P<0.05). The apoptotic rate of the cells increased significantly and the expression of apoptosis promoting protein puma, BMF and p27kip1 in the cells increased (P<0.05); the 50% inhibitory concentration (IC50) of drug resistance cells in the inhibitor group was significantly lower than that in the blank control group and the negative control group (P<0.05). Conclusion: miR-221/222 can increase the resistance of MDA-MB-231/DOX cells to DOX, [ABSTRACT FROM AUTHOR]