Injectable 2D‐MoS2‐integrated Bioadhesive Hydrogel as Photothermal‐Derived and Drug‐Delivery Implant for Colorectal Cancer Therapy

An injectable, adhesive hydrogel integrating 2D-MoS₂ and 5-fluorouracil (AlgNB/MoS₂/5-FU) is developed for near-infrared-triggered photothermal therapy and localized drug delivery. The adhesive hydrogel demonstrates superior tumor anchoring, efficient photothermal conversion, and synergistic inhibition of colorectal cancer progression, offering a promising strategy for advanced CRC treatment.

Abstract

Photothermal therapy (PTT) combined with chemotherapy using hydrogel as a delivery platform is considered a promising strategy for the treatment of advanced colorectal cancer (CRC). However, maintaining the stability of photo-absorbing agents (PTA) in the hydrogel and ensuring that the hydrogel remains anchored to the tumor tissue presents significant challenges. Herein, this work introduces an injectable 2D molybdenum disulfide (2D-MoS₂)-integrated adhesive hydrogel, specifically N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitro-sophenoxy) butanamide-linked sodium alginate-MoS₂-5-fluorouracil (AlgNB/MoS₂/5-FU). This hydrogel functions as a near-infrared light (NIR)-triggered photothermal and drug-delivery implant for CRC treatment. The MoS₂ nanosheets maintain superior dispersibility in the hydrogel and exhibit a highly efficient NIR-triggered photothermal effect. Importantly, the aldehyde group in AlgNB also imparted tissue adhesion to the hydrogel, the adhesive hydrogel is used to infiltrate and anchor within tumor tissue. The injectable adhesive AlgNB/MoS₂/5-FU hydrogel shows remarkable efficacy in inhibiting SW480 cells proliferation and promoting colorectal tumor regression by triggering PTT and delivering the 5-FU drug in both in vitro and in vivo studies. The potential synergistic mechanism of PTT and 5-FU chemotherapy may contribute to inhibiting DNA repair and enhancing a robust immune response. Therefore, this research provides valuable strategic insights for the synergistic treatment of localized CRC.