Programmable nanomotor system responsively and chemotactically captures tumor associated antigens for enhanced in situ cancer vaccine

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 (_DDMSN@_MOMV^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, _DDMSN@_MOMV^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 _DDMSN@_MOMV^PF detected DNA gradient and propelled nanoparticles chemotactically capturing TAAs. In vivo results indicated that _DDMSN@_MOMV^PF suppressed both primary and distant tumors and elicited immune memory effects to prevent tumor recurrence.

Cancer immunotherapy; Dendritic mesoporous silica nanoparticles; Nanomotors; Outer membrane vesicles; TAA capture.