Physicochemical Cues Steering Spiky Mn/MoOx Nanocarriers to Mimic Oncolytic Virus for Potentiating Cancer Immunotherapy

Abstract The approval of oncolytic viruses as antigen‐agnostic cancer vaccines provides a paradigm shift for immunotherapy. However, a delicate balance between safety and immunogenicity whether native or engineered oncolytic viruses remains elusive and further compounded by oncolysis‐induced immunosuppression. To address these dilemmas, the de novo design and synthesis of oncolytic viruses‐inspired nanoplatform are proposed by emulating desirable nanostructure and bioactivity for effective cancer immunotherapy. Initially, the influence of MoOx nanoparticles with varying physical morphologies on siRNA transfection are explored, wherein the virus‐inspired MoOx nanoparticles with spiky surfaces (Spi‐MoOx) are well positioned to serve as siRNA vectors to present the highest transfection efficacy. Given the preexisting immune suppression, defect engineering is incorporated into Spi‐MoOx through Mn dopants (Spi‐Mn/MoOx), in an effort to participate in tumor adaptation to hypoxia and maximize the oncolytic potency, while retaining favorable safety profiles. More importantly, the engineered oncolytic viruses hold considerable promise to function as a universal platform that enables any gene to be modulated precisely, allowing the selective activation of various pathways. Collectively, the study offers insights into the biomimetic synthesis and bioactivity of biological system through manipulating the physicochemical cues, while carrying significant implications to propel artificial oncolytic agents from the laboratory to clinical settings.