Cell-Derived Biogenetic Gold Nanoparticles for Sensitizing Radiotherapy and Boosting Immune Response against Cancer

The biosynthesis of nanomedicine has gained enormous attention and exhibited promising prospects, while the underlying mechanism and advantage remain not fully understood. Here, a cell-reactor based on tumor cells is developed to obtain biogenetic gold nanoparticles (Au@MC38) for sensitizing radiotherapy and boosting immune responses. It demonstrates that the intracellular biomineralization and exocytosis process of Au@MC38 can be regulated by the cellular metabolites level and other factors, such as glutathione and reactive oxygen species (ROS), autophagy, and UV irradiation. The elucidation of mechanisms may promote the understanding of interaction principles between nanoparticles and biosystems in the process of biosynthesis. Combined with radiotherapy, Au@MC38 strengthens the radiation-induced DNA damage and ROS generation, thus aggravating cell apoptosis and necrosis. Benefiting from homologous targeting and transcytosis effect, Au@MC38 demonstrates good tumor distribution. Local radiation-induced immunogenic cell death initiates an effective immune response. Especially, CD8a(+) dendritic cells are significantly increased in mice that received combinatorial treatment. This radio-sensitization strategy has demonstrated the effective inhibition on primary and metastatic tumors, and achieved satisfactory survival benefit in combinatorial with immune checkpoint blockade. Thus, this bio-inspired synthetic strategy may impulse the development of biosynthesis and its therapeutic applications, contributing to a non-invasive and efficient modality for nanomedicine exploitation.

Automated summary

The biosynthesis of nanomedicine using tumor cells as a basis has shown potential for enhancing radiotherapy sensitivity and promoting immune responses. Au@MC38's intracellular biomineralization and exocytosis process can be regulated by cellular metabolites and other factors, potentially leading to effective immune responses through radio-sensitization. Additionally, the strategy has demonstrated an effective inhibition of primary and metastatic tumors, as well as improving survival benefits when combined with immune checkpoint blockade.