Nanomotors activating both cGAS-STING pathway and immune checkpoint blockade for tumor therapy and bioimaging

Cellular innate immune response is closely related to cGAS-STING pathway and PD-1/PD-L1 immune checkpoint blockade. The lack of tissue penetration of STING agonists and nanomedicines in conventional approaches reduces their immunotherapeutic efficacy. At the same time, because the cGAS-STING signaling pathway is silent in many breast cancer cells, it cannot play its role. To address these challenges, here, we developed a silica nanomotor based on bubble propulsion. Its hollow structure was packed with the photosensitizer Ce6 molecule. Under 808 nm laser irradiation, Ce6 produced ¹O₂, which lead to intracellular DNA damage and further activated the cGAS-STING pathway, stimulating the maturation of DC cells, and enhancing the tumor infiltration of CD8⁺ T cells. The nanomotor had an asymmetrical structure. One side of the nanomotor was modified with Pt nanoparticle. This asymmetric modification can catalyze H₂O₂ in the environment, producing an asymmetric concentration of O₂, which realized the bubble driving nanomotor movement and enhances penetration into breast cancer cells of nanomotor. The other side of the nanomotor was modified the LXL-1 aptamer, triphenylphosphine and peptide CLP002. Peptide CLP002 specifically bound residues of PD-L1 interaction with PD-1, blocked the mutual binding between PD-1 and PD-L1, and further improved the immune response ability of tumor infiltrating T cells. In this study, we developed a multi-pronged immunotherapy strategy of intelligent target finding, breaking through the physiological barrier through kinetic energy, accurately intervening the target and bioimaging, providing a new idea for breast cancer cells targeted therapy.