MnCaCs-Biomineralized Oncolytic Virus for Bimodal Imaging-Guided and Synergistically Enhanced Anticancer Therapy

Oncolytic adenovirus (OA) is an ideal candidate for clinical anticancer treatment, because it can specifically replicate in tumor cells with high titer. However, its systemic administration is still hindered, because of severely compromised antitumor efficacy. Herein, an engineered OA was innovatively developed by enwrapping OA with calcium and manganese carbonates (MnCaCs) biomineral shell, which could protect the virus from removal of the host immune system and prolong its in vivo circulation. Upon accumulating in tumor sites, MnCaCs readily dissolved under the acidic microenvironment, releasing Mn²⁺ that could convert endogenous H₂O₂ into oxygen (O₂) and then enhance the duplication ability of OA, thus significantly increased the antitumor efficacy. Meanwhile, Mn²⁺ and the increased O₂ individually endowed the T1 modal magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) feasibility, providing real-time monitoring information for the therapy. This versatile engineered OA demonstrated its promise for visible and efficient oncolytic virotherapy by systemic administration.