Intravesical In Situ Immunostimulatory Gel for Triple Therapy of Bladder Cancer.

Bladder cancer displays multiple biological features aided in drug resistance; therefore, single therapy fails to induce complete tumor regression. To address this issue, various kinds of cell death of cancer cells as well as restoring tumor immune microenvironment need to be taken into consideration. Here, we introduce a gel system termed AuNRs&IONs@Gel, which target-delivers a combination of photothermal, ferroptotic, and immune therapy through intravesical instillation. AuNRs&IONs@Gel consists of a gel delivery platform, embedded gold nanorods (AuNRs), and iron oxide nanoparticles (IONs). The targeted delivery gel platform provides dextran aldehyde-selective adhesion with cancer collagen. In this condition, photothermal therapy can be performed by gold nanorods (AuNRs) under imaging-guided near-infrared radiation. Local high concentrations of IONs can be absorbed by cancer cell to induce ferroptosis. Moreover, tumor-associated macrophages which often display an immune-suppressive M2-like phenotype will be repolarized by IONs into the antitumor M1-like phenotype, exerting a direct antitumor effect and professional antigen presentation of dead cancer cells. This process triggers a potent immune response of innate and adapt immunities to protect tumor rechallenge in long terms. Our triple-therapy strategy employs FDA-approved nanoparticles to inhibit bladder cancer which may possess great potential for clinical translation.