NO‐Driven Janus Nanomotor Enhances T‐Cell Infiltration by Reconstructing Tumor‐Associated Blood and Lymphatic Vessels

The effectiveness of antitumor immunotherapy is limited to immune cell infiltration into solid tumors, primarily via T‐cell migration through tumor blood vessels. This study introduces a multifunctional nitric oxide (NO)‐driven hollow gold Janus nanomotor (HAM) designed to promote tumor blood vessel normalization and increase T‐cell infiltration, thereby enhancing the immune response against tumors. It is revealed that self‐generated NO facilitates the penetration of HAM into tumors and increases pericyte coverage of blood vessels, thereby enhancing intratumoral T‐cell infiltration. HAMs then induce and capture whole‐tumor antigens to enhance T‐cell activation as an in situ cancer vaccine. Additionally, vascular endothelial growth factor C (VEGFC) is used in combination to induce functional lymphangiogenesis, aiding dendritic cell (DC) migration of tumor‐draining lymph nodes (TDLNs). In B16F10 mice, the proportion of tumor‐infiltrating T cells increased from 0.5% to 27.4% while that of mature DCs in TDLNs increased from 4.3% to 16.6%, markedly improving tumor‐killing effects. Similar outcomes are observed in 4T1 tumor‐bearing mice. Collectively, this study highlights the importance of paving the way for intratumoral infiltration of immune cells via nanomotors, which provides a novel idea for enhancing antitumor immunotherapeutic effects.