Chitosan Thermosensitive Hydrogel Based on DNA Damage Repair Inhibition and Mild Photothermal Therapy for Enhanced Antitumor Treatment

The DNA damage repair of tumor cells limits the effectof photothermaltherapy (PTT), and high temperatures induced by PTT can damage adjacentnormal tissues. To overcome these limitations, we developed a novelcomposite hydrogel (OLA-Au-Gel) based on chitosan (CS) and & beta;-glycerophosphate(& beta;-GP), which encapsulated olaparib-liposomes (OLA-lips) andCS-capped gold nanoparticles (CS-AuNPs). OLA-Au-Gel achieved the combinationof mild PTT (mPTT) by CS-AuNPs and tumor DNA damage repair inhibitionby OLA. The hydrogel showed good biocompatibility, injectability,and photothermal response. Under near-infrared laser irradiation,OLA-Au-Gel inhibited the proliferation of tumor cells, induced thegeneration of reactive oxygen species in vitro, andeffectively inhibited the growth of breast tumors in vivo. OLA-Au-Gel shows a promising application prospect for inhibitingtumor development and improving the antitumor effect. Collectively,we propose a novel strategy for enhanced antitumor therapy based onthe combination of mPTT and DNA damage repair inhibition.

Automated summary

To overcome the limitations of DNA damage repair in tumor cells and the damaging effect of high temperatures induced by photothermal therapy (PTT) on adjacent normal tissues, a novel composite hydrogel (OLA-Au-Gel) was developed. OLA-Au-Gel achieved mild PTT (mPTT) through CS-AuNPs and inhibited tumor DNA damage repair through OLA. The hydrogel showed good biocompatibility, injectability, and photothermal response, effectively inhibiting tumor growth both in vitro and in vivo. OLA-Au-Gel holds promising application prospects for tumor inhibition and enhancing the antitumor effect.