Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

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AbstractDoxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells.Epigallocatechin photos de carhartt wip store toulouse gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX.Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells.

In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells.In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA.The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR).

Additionally, we investigate the anti-drug resistant mechanism by Western Blot.The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay.In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse quad port fittings the MDR in tumor cells.

It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.