Engineering glutathione-responsive near-infrared polymeric prodrug system for fluorescence imaging in tumor therapy

Abstract

The release and biodistribution of drugs in the body have an important impact on tumor diagnosis and treatment. Near-infrared (NIR) fluorescent active fluorophores with good photostability are used to detect drug release and perform in vivo imaging. Here, we developed a glutathione-responsive NIR prodrug POEGMA-b-P(CPT-CyOH) (PCC) for effective cancer diagnosis and treatment, whereby the camptothecin (CPT) and NIR fluorophore CyOH in PCC are connected by disulfide bonds. In vitro experiments confirmed that PCC was quickly taken up by cells. The high concentration of tumor intracellular glutathione caused the cleavage of the PCC disulfide bonds, leading to the release of the chemotherapeutic drug CPT, indicating that PCC can promote apoptosis. Moreover, owing to the fluorescent properties of CyOH, PCC was successfully used for in vivo imaging to observe the drug penetration and enrichment capabilities in tumors. Finally, PCC successfully inhibited tumor growth, indicating that the prodrug has a good anti-tumor effect. This work provides new strategies for chemical drug delivery and precise cancer treatment.

Keywords: Cancer diagnosis and treatment; Chemotherapy; Drug delivery; Glutathione-responsive prodrug; Stimuli-responsive.