The multimodal anti-tumor effect of cisplatin nanoparticles loaded with bacterial antibodies in combination with radiotherapy: targeting hypoxic tumor and reshaping of the immune microenvironment

The hypoxic tumor microenvironment (TME) is a key factor contributing to the poor efficacy of traditional radiotherapy (RT) and chemotherapy in the treatment of solid tumors. Here, we have developed a chitosan nanosystem consisting of cisplatin (CDDP) nanoparticles (NPs) modified with mono-antibodies (mAbs) against Bifidobacterium (Bi) (mAb@CDDP-NPs). Bi is designated as a “target” to be implanted in the hypoxic TME. Before administering nanosystem therapy, Bi was pre-implanted in the hypoxic region of the tumor. The mAb@CDDP-NPs then achieved targeted enrichment in the weakly acidic hypoxic region where Bi had localized. Subsequently, the chitosan-encapsulated structure of mAb@CDDP-NPs swelled and ruptured, ultimately releasing CDDP. The new therapeutic method of mAb@CDDP-NPs + RT has been proven to have an excellent targeted anti-tumor effect in the CT26 and 4 T1 tumor-bearing mouse models. This method not only possesses the anti-tumor effects of RT and chemotherapy, but also effectively regulates immunosuppressive TME. It presents as an increase in infiltration of mature DCs, CD8 + T, and NK cells, and a decrease in infiltration of MDSC cells. Moreover, the mAb@CDDP-NPs nanosystem significantly reduces the adverse reactions of CDDP. The successful construction of the mAb@CDDP-NPs nanosystem and the development of a novel treatment model that combines mAb@CDDP-NPs with RT for anti-tumor therapy is expected to provide new insights for the treatment of solid tumors.