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

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Angiogenesis regulation is crucial for effective anticancer therapy, but current anti-angiogenic therapies face challenges due to cancer recurrence.
• Existing therapies often fail because tumors compensate by expressing different angiogenic mediators, limiting the efficacy of angiogenesis inhibition agents (AIAs).

Purpose of the Study:

• To develop a new strategy for engineering efficient angiogenesis inhibition agents (AIAs) using a near-infrared-II (NIR-II) responsive hydrogel system.
• To investigate the potential of NIR-II light to control nitric oxide (NO) generation for reprogramming the tumor microenvironment (TME) and inhibiting tumor growth.

Main Methods:

• Fabrication of a hydrogel incorporating a nitric oxide (NO) precursor (BNN6) and 2D WO2.9 nanosheets (WB@hydrogel).
• Engineered WO2.9 nanosheets exhibit a narrowed bandgap for NIR-II light absorption, enabling controlled NO generation based on irradiation time and intensity.
• Evaluation of the NO-releasing hydrogel's effect on wild-type p53 protein expression and the transcriptional regulation of angiogenic factors within the TME in a murine tumor model.

Main Results:

• The WB@hydrogel system demonstrated efficient NO generation under NIR-II irradiation.
• The generated NO activated wild-type p53 and reversed the pro-angiogenic TME to an anti-angiogenic state.
• Significant tumor growth inhibition (TGI) and excellent anti-recurrence efficiency were observed in the murine tumor model.

Conclusions:

• The developed NIR-II responsive hydrogel system offers a promising strategy for controlling NO release and reprogramming the TME.
• This approach presents a novel and effective method for developing advanced angiogenesis inhibition agents (AIAs) with reduced cancer recurrence.
• The study highlights the potential of combining nanotechnology and controlled NO release for enhanced anticancer therapy.