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

Abstract

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.