NIR‐II Responsive Hydrogel as an Angiogenesis Inhibition Agent for Tumor Microenvironment Reprogramming

Abstract Regulation of angiogenesis is a great challenge for effective anticancer therapy. Generally, anti‐angiogenic therapies are focused on inhibition of inducers involved in pro‐angiogenic communication pathways. Despite the great potential of anti‐angiogenic therapy, engineering efficient angiogenesis inhibition agents (AIAs) is still a formidable challenge, since most anti‐angiogenic therapies are limited due to the cancer recurrence via compensatory expression of different angiogenic mediators. Herein, we present a new strategy of near‐infrared‐II (NIR‐II) responsive hydrogel AIAs, constructed by incorporation of nitric oxide (NO) precursor (BNN6) and 2D WO 2.9 nanosheets within hydrogel (WB@hydrogel). Because of the defect/2D engineering, the bandgap of the WO 2.9 nanosheets narrows, which extends the absorption to the NIR‐II region. It offers a favorable NIR‐II controlled manner for NO generation through irradiation time and light intensity. The continuous supply of NO can activate the expression of wild‐type p53 protein and further reverse the transcriptional expression of pro‐ and anti‐angiogenic factors of the tumor microenvironment (TME), subsequently alternating pro‐angiogenic TME to anti‐angiogenic TME. In the murine tumor model, this method achieved high tumor growth inhibition (TGI) rate and excellent anti‐recurrence efficiency.