Dually responsive nanogels as smart carriers for improving the therapeutic index of doxorubicin for breast cancer

Abstract

Nanocarriers can significantly improve the therapeutic index of drug in cancer therapy. At present, parenteral administration of free doxorubicin (Dox) to treat breast tumor produces severe side effects including cardiotoxicity. This work reports the preparation of N-isopropyacrylamide/acrylic acid nanogels (NGs), NIPA/AAc NGs, crosslinked by a disulfide-bearing monomer, which can be used as smart carriers of Dox for cancer therapy. The NGs prepared showed high load percentage of Dox through ionic interaction. The size of the NGs in simulated physiological medium was ideal to be applied as a carrier in cancer therapy. In vitro release studies demonstrated that the designed drug delivery system (DDS) can active the release of a large amount of drug in simulated intracellular medium in response to redox potential and pH, but with minimal release in simulated plasma conditions. Cellular uptake studies showed that NGs loaded with Dox can be internalized in human breast cancer cell line MDA-MB-231. Cell toxicity studies demonstrate that unloaded NGs are nontoxic for human breast cancer cell line MDA-MB-231 and mouse breast cancer cell line 4T1. In addition, it was shown that Dox-loaded NGs are more toxic for the cell than free Dox for both cell lines. In vivo studies in mice showed that Dox-loaded NGs improve the drug therapeutic index with a notable decrease in tumor size, as compared with a similar dose of free Dox. Finally, the development of this nanoformulation could improve the results and patient compliance in chemotherapy treatments of breast cancer.