International Journal of Nanomedicine (Apr 2020)
Paclitaxel/IR1061-Co-Loaded Protein Nanoparticle for Tumor-Targeted and pH/NIR-II-Triggered Synergistic Photothermal-Chemotherapy
Abstract
Li He,1,* Fangzhen Qing,2,* Maode Li,3 Daitian Lan3 1Department of Thyroid and Breast Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (East Hospital), Chengdu 610100, Sichuan, People’s Republic of China; 2Department of Stomatology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (East Hospital), Chengdu 610100, Sichuan, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (East Hospital), Chengdu 610100, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Daitian LanDepartment of Hepatobiliary and Pancreatic Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (East Hospital), Chengdu 610100, Sichuan, People’s Republic of ChinaTel +86-18349176311Email [email protected]: The aim of this study was to develop an “all-in-one” nanoplatform that integrates at the second near-infrared (NIR-II) region dye IR1061 and anticancer drug paclitaxel (PTX) into an apoferritin (AFN) nanocage (IR-AFN@PTX). Simultaneously, folic acid (FA), tumor target molecule, was conjugated onto IR-AFN@PTX to be IR-AFN@PTX-FA for tumor-targeted and pH/NIR-II-triggered synergistic photothermal-chemotherapy.Methods: IR1061 was firstly reacted with PEG and then conjugated with AFN to be IR-AFN. Then, FA was conjugated onto the surface of IR-AFN to be IR-AFN-FA. At last, PTX was incorporated into IR-AFN-FA to fabricate a nanoplatform IR-AFN@PTX-FA. The NIR-II photothermal properties and pH/NIR-II triggered drug release were evaluated. The ability of IR-AFN@PTX-FA to target tumors was estimated using optical bioluminescence. In vitro and in vivo synergistic therapeutic effects of pH/NIR-II-triggered and tumor-targeted photothermal-chemotherapy were investigated in 4T1 tumor model.Results: IR-AFN@PTX-FA showed excellent water solubility and physiological stability, which significantly enhanced the solubility of both IR1061 and PTX. After 5 min of laser irradiation at 1064 nm, IR-AFN@PTX-FA exhibited an effective photothermal effect compared with laser irradiation at 808 nm, even when blocked with 0.6 cm thick chicken breast. Cellular uptake experiments showed IR-AFN@PTX-FA utilized clathrin-mediated and caveolae-mediated endocytosis pathways to enter 4T1 cells, and was then delivered by the endosome to the lysosome. NIR-II laser irradiation and pH could synergistically trigger PTX release, inducing significant tumor inhibition in vitro and in vivo.Conclusion: As a novel “all-in-one” nanoplatform, IR-AFN@PTX-FA was found to selectively target tumors and showed very efficient NIR-II photothermal effects and pH/NIR-II triggered drug release effects, showing a remarkable, synergistic photothermal-chemotherapy effect.Keywords: IR1061, second near-infrared window, paclitaxel, apoferritin, “all-in-one” nanoplatform
