A nuclear targeted dual-photosensitizer for drug-resistant cancer therapy with NIR activated multiple ROS. Issue 7 (23rd March 2016)

• Record Type: Journal Article
• Authors: Yu, Zhengze; Pan, Wei; Li, Na; Tang, Bo
• Is Part Of: Chemical science. Volume 7:Issue 7(2016:Jul.)
• Page Start: 4237
• Page End: 4244
• Publication Date: 2016-03-23
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6sc00737f
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A nuclear targeted dual-photosensitizer was developed for photodynamic therapy against multidrug resistant cancer. Multiple reactive oxygen species (ROS) could be generated in the nucleus to directly break DNA double strands with a single 980 nm NIR laser irradiation, regardless of drug resistance. Abstract : Photodynamic therapy against cancer, especially multidrug resistant cancer, is limited seriously due to the efflux of photosensitizer molecules by P-glycoprotein, which leads to insufficient production of reactive oxygen species (ROS). For the purpose of abundant ROS generation and effective therapeutic response, herein, we firstly design and fabricate a nuclear targeted dual-photosensitizer for photodynamic therapy against multidrug resistant cancer. Molecule-photosensitizer Ce6 was selected and modified on the surface of core/shell structure nano-photosensitizer upconversion@TiO2 and then nuclear targeted peptides TAT were anchored for nuclear targeting. Through selective doping of rare earth elements Er and Tm, multiple ROS (˙OH, O2 ˙ −, and 1 O2 ) can be generated for the dual-photosensitizer and realize their functions synergistically using a single 980 nm NIR excitation. The nano-sized photosensitizer accompanied with nuclear targeting can effectively generate multiple ROS in the nucleus regardless of P-glycoprotein and directly break DNA double strands, which is considered as the most direct and serious lesion type for cytotoxic effects. Therefore, enhanced photodynamic therapy can be achieved against multidrug resistant cancer. In vitro and in vivo studies confirmed the excellent therapeutic effect of the dual-photosensitizer against cancer cells and drug-resistant cancer cells, as well as xenograft tumor models.