RRC ID 58582
Author Wu H, Wang C, Sun J, Sun L, Wan J, Wang S, Gu D, Yu C, Yang C, He J, Zhang Z, Lv Y, Wang H, Yao M, Qin W, Wang C, Jin H.
Title Self-Assembled and Self-Monitored Sorafenib/Indocyanine Green Nanodrug with Synergistic Antitumor Activity Mediated by Hyperthermia and Reactive Oxygen Species-Induced Apoptosis.
Journal ACS Appl Mater Interfaces
Abstract Liver cancer is a leading cause of cancer morbidity and mortality worldwide, especially in China. Sorafenib (SRF) is currently the most commonly used systemic agent against advanced hepatocellular carcinoma (HCC), which is the most common type of liver cancer. However, HCC patients have only limited benefit and suffer a serious side effect from SRF. Therefore, new approaches are urgently needed to improve the therapeutic effectiveness of SRF and reduce its side effect. In our current study, we developed a self-imaging and self-delivered nanodrug with SRF and indocyanine (ICG) to improve the therapeutic effect of sorafenib against HCC. With the π-π stacking effect between SRF and ICG, a one-step nanoprecipitation method was designed to obtain the SRF/ICG nanoparticles (SINP) via self-assembly. Pluronic F127 was used to shield the SINP to further improve the stability in an aqueous environment. The stability, photothermal effect, cell uptake, ROS production, cytotoxicity, tumor imaging, and tumor-targeting and tumor-killing efficacy of the SINP were evaluated in vitro and in vivo by using an HCC cell line Huh7 and its xenograft tumor model. We found that our designed SINP showed monodisperse stability and efficient photothermal effect both in vitro and in vivo. SINP could rapidly enter Huh7 cells and achieve potent cytotoxicity under near-infrared (NIR) laser irradiation partly by producing a great amount of reactive oxygen species (ROS). SINP had significantly improved stability and blood half-life, and could specifically target tumor via the enhanced permeability and retention (EPR) effect in vivo. In addition, SINP showed improved cytotoxicity in both subcutaneous and orthotopic HCC implantation models in vivo. Overall, this rationally designed sorafenib delivery system with a very high loading capacity (33%) has considerably improved antitumor efficiency in vitro and could completely eliminate subcutaneous tumors without any regrowth in vivo. In conclusion, our self-imaging and self-delivered nanodrug could improve the efficacy of SRF and might be a potential therapy for HCC patients.
Volume 11(47)
Pages 43996-44006
Published 2019-11-27
DOI 10.1021/acsami.9b18086
PMID 31682099
MeSH Animals Antineoplastic Agents / administration & dosage* Antineoplastic Agents / chemistry Apoptosis / drug effects* Cell Line, Tumor Combined Modality Therapy Drug Synergism Female Humans Hyperthermia, Induced* Indocyanine Green / administration & dosage* Indocyanine Green / chemistry Mice, Inbred BALB C Mice, Nude Neoplasms / drug therapy* Neoplasms / metabolism Neoplasms / physiopathology Neoplasms / therapy Reactive Oxygen Species / metabolism* Sorafenib / administration & dosage* Sorafenib / chemistry
IF 8.456
Times Cited 1
Human and Animal Cells HuH-7