Biomacromolecules, Vol.19, No.6, 2034-2042, 2018
Radiotherapy-Sensitized Tumor Photothermal Ablation Using gamma-Polyglutamic Acid Nanogels Loaded with Polypyrrole
Development of versatile nanoscale platforms for cancer diagnosis and therapy is of great importance for applications in translational medicine. In this work, we present the use of gamma-polyglutamic acid (gamma-PGA) nanogels (NGs) to load polypyrrole (PP gamma) for thermal/photoacoustic (PA) imaging and radiotherapy (RT)-sensitized tumor photothermal therapy (PTT). First, a double emulsion approach was used to prepare the cystamine dihydrochloride (Cys)-cross-linked gamma-PGA NGs. Next, the cross-linked NGs served as a reactor to be filled with pyrrole monomers that were subjected to in situ oxidation polymerization in the existence of Fe(III) ions. The formed uniform PP gamma-loaded NGs having an average diameter of 38.9 +/- 8.6 nm exhibited good water-dispersibility and colloid stability. The prominent near-infrared (NIR) absorbance feature due to the loaded PP gamma endowed the NGs with contrast enhancement in PA imaging. The hybrid NGs possessed excellent photothermal conversion efficiency (64.7%) and stability against laser irradiation, and could be adopted for PA imaging and PTT of cancerous cells and tumor xenografts. Importantly, we also explored the cooperative PTT and X-ray radiation-mediated RT for enhanced tumor therapy. We show that PTT of tumors can be more significantly sensitized by RT using the sequence of laser irradiation followed by X-ray radiation as compared to using the reverse sequence. Our study suggests a promising theranostic platform of hybrid NGs that may be potentially utilized for PA imaging and combination therapy of different types of tumors.