In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles

• DOI: 10.1021/acs.biomac.5b00944
• Publication Date: 2015-10-09T21:27:18Z
• Authors: Sung Han Kim; Jung Eun Lee; Shazid Md. Sharker; Ji Hoon Jeong; Insik In; Sung Young Park
• Keywords: Mice, Inbred BALB C; Spectroscopy, Near-Infrared; Mice, Nude; Biocompatible Materials; Hydrogen-Ion Concentration; Phototherapy; 01 natural sciences; Madin Darby Canine Kidney Cells; Nanocomposites; Polyethylene Glycols; 0104 chemical sciences; 3. Good health; Mice; Dogs; Cell Line, Tumor; Neoplasms; Animals; Humans; Methacrylates; Nanoparticles; Graphite; Tissue Distribution; Hyaluronic Acid

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.