Reactive Oxygen Species-Responsive Nanoparticles Based on PEGlated Prodrug for Targeted Treatment of Oral Tongue Squamous Cell Carcinoma by Combining Photodynamic Therapy and Chemotherapy

• DOI: 10.1021/acsami.8b08269
• Publication Date: 2018-08-14T14:21:51Z
• Authors: Shurui Shi; Lianyun Zhang; Mengqi Zhu; Guoyun Wan; Changyi Li; Juan Zhang; Yue Wang; Yinsong Wang
• Keywords: Mice; Photochemotherapy; Doxorubicin; Carcinoma, Squamous Cell; Animals; Nanoparticles; Prodrugs; 02 engineering and technology; Reactive Oxygen Species; 0210 nano-technology; 01 natural sciences; Tongue Neoplasms; 0104 chemical sciences

In this study, a reactive oxygen species (ROS)-responsive nanoparticle system was designed for combining photodynamic therapy (PDT) and chemotherapy for oral tongue squamous cell carcinoma (OTSCC)-targeted treatment. A PEGlated prodrug (RPTD) of doxorubicin (DOX) via thioketal linkage and cRGD peptide modification was synthesized and then used to prepare nanoparticles for encapsulating photosensitizer hematoporphyrin (HP). Thus, the obtained HP-loaded RPTD (RPTD/HP) nanoparticles had a regular spherical shape and small size, approximately 180 nm. The RPTD/HP nanoparticles showed a remarkable PDT efficiency and successfully induced ROS generation upon laser irradiation both in vitro and in vivo. DOX exhibited significant ROS-responsive release property from RPTD/HP nanoparticles because of the rupture of the thioketal linker. In OTSCC cells, RPTD/HP nanoparticles were efficiently internalized and showed potent effects on cell growth inhibition and apoptosis induction after laser irradiation. In OTSCC tumor-bearing mice, RPTD/HP nanoparticles displayed excellent tumor-targeting ability and notably suppressed tumor growth through multiple mechanisms after local laser irradiation. Taken together, we supplied a novel therapeutic nanosystem for OTSCC treatment through combining PDT and chemotherapy.