Breast cancer is still a major worldwide health concern.
Although breast cancer is still a major worldwide health concern, new, promising therapeutic options are now available because to the development of carefully considered medication combinations and sophisticated biocompatible delivery methods. Based on the selective tumour apoptotic impact of Rosuvastatin (RST), we repurposed it here and coupled it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). Inspired by the stealth feature of sodium alginate (ALG) and the cancer cell targeting ability of Lactoferrin (LF), this synergistic three-drug combination was combined into protein polysaccharide Nano hybrids. ALG was conjugated to PMT, combined with LF, which was conjugated to RST, and then inserted physically into core shell Nano hybrids made of genipin and LF. The PMT-ALG/LF-RST Nano hybrids with cross-linked HK loading showed a reasonable drug loading of 7.86, 5.24, and 6.11% for RST, PMT, and HK, respectively. It showed improved cellular absorption by MCF-7 cells and an eight-fold reduction in IC50 when compared to the free drug combination. The advantage of the triple cocktail-loaded Nano hybrids was proven by their in vivo anticancer effectiveness in a breast cancer-bearing mice model. A potential, biocompatible method for efficient breast tumour suppression is provided by our rationally engineered triple drug-loaded protein/polysaccharide nano hybrids.