EXM/RES-ZNCs showed enhanced cytotoxicity against MCF-7 and 4T1 breast cancer cells compared with free drug combination with higher selectivity to cancer cells rather than normal fibroblasts. In vivo, crosslinked EXM/RES-ZNCs markedly reduced the percentage increase of Ehrlich ascites mammary tumor volume in mice by 2.4-fold compared with free drug combination.