Nanoparticles for Near-Infrared Light-Driven Singlet Oxygen and CO Gas Cogeneration for Pancreatic Adenocarcinoma Therapy

Developing photocatalytic medicine for targeted therapy is intriguing but still remains a great challenge. Herein, we developed a nanophotosensitizer (c-PDMS) decorated with pancreatic adenocarcinoma (PAC)-targeting DNA aptamer Xq-2D (abbreviated as Xq-2D/c-PDMS) for enhanced photodynamic–gas synergistic therapy of PAC. c-PDMS is constructed by poly­[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta­[2,1-b/3,4-b′]­dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (OSP) integrated into dendritic mesoporous silica (DMS) through a one-step method and further loaded with the CORM-401 prodrug as the CO donor. Our prepared c-PDMS can produce ¹O₂ and then oxidate the CORM-401 prodrug to release CO gas under near infrared (NIR) laser irradiation. After being decorated by Xq-2D aptamer-HS with MAL-PEG-NHS, the resultant Xq-2D/c-PDMS showed good biocompatibility, active targeting, and high cellular uptake ability by PAC cells compared to c-PDMS alone, which led to an efficient killing effect to fight against PAC cancer cells through ¹O₂ oxidization and CO-mediated mitochondrial respiration inhibition. Furthermore, the excellent antitumor efficiency of Xq-2D/c-PDMS in vivo with minimized side effects was clarified by the analysis of tumor volume and weight, H&E staining of tumors, biochemical indexes, and weight loss after NIR laser irradiation. This study provides an efficient synergistic strategy for PAC therapy.