Abstract
In situ cancer vaccines that utilize the body's own tumor-associated antigens (TAAs) to induce tumor-specific adaptive immune responses are emerging as a promising strategy in cancer therapy. However, the rapid clearance of TAAs due to innate immune system hinders the development of effective antitumor immunity. To address this challenge, we developed a nanomotor system ((D)DMSN@(M)OMV(PF)) as an in situ cancer vaccine capable of chemotactically capturing TAAs, significantly inhibiting the rapid clearance of TAAs and enhancing cancer immunotherapy. In response to acid tumor microenvironment, (D)DMSN@(M)OMV(PF) exfoliated folate acid-attached, mitoxantrone-embedded bacterial outer membrane vesicle (OMV) fragments, which could be specifically taken up by tumor cells to induce immunogenic cell death (ICD) and release DNA-associated TAAs. Subsequently, the exposed DNase on (D)DMSN@(M)OMV(PF) detected DNA gradient and propelled nanoparticles chemotactically capturing TAAs. In vivo results indicated that (D)DMSN@(M)OMV(PF) suppressed both primary and distant tumors and elicited immune memory effects to prevent tumor recurrence.