Indocyanine Green and Curcumin Co-Loaded Nano-Fireball-Like Albumin Nanoparticles Based on Near-Infrared-Induced Hyperthermia for Tumor Ablation

Abstract

Phuong Thi Thu Pham,1 Xuan Thien Le,1 Hanju Kim,1 Hwang Kyung Kim,1 Eun Seong Lee,2 Kyung Taek Oh,3 Han-Gon Choi,4 Yu Seok Youn1 1School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea; 2Division of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea; 3College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea; 4College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 15588, Republic of KoreaCorrespondence: Yu Seok Youn Tel +82-31-290-7785Email ysyoun@skku.eduBackground: Indocyanine green (ICG) has received considerable interest as a biocompatible organic photothermal agent, and curcumin (Cur) is considered an attractive natural chemopreventive and chemotherapeutic compound. However, the in vivo applicability of ICG and Cur is significantly restricted by their poor ability to target tumors and their extremely low solubility.Materials and Methods: To address these problems, ICG/Cur-loaded albumin nanoparticles (ICG-BSA-Cur-NPs) based on the nabTM (nanoparticle albumin-bound) technology were applied to neuroblastomas in vivo.Results: The fabricated ICG-BSA-Cur-NPs were found to be spherical, ∼ 150 nm in size and highly dispersible and stable in aqueous solution. Approximately 80% of the incorporated ICG and Cur were gradually released from the NPs over 48 h. All formulations of ICG-BSA-Cur-NPs (5∼ 20 μg/mL) showed efficient hyperthermia profiles (up to 50– 60°C within 5 min) in response to 808-nm NIR laser irradiation in vitro and in vivo. Notably, ICG-BSA-Cur-NPs illuminated with 808-nm laser irradiation (1.5 W/cm2) showed excellent cytotoxicity toward N2a cells in vitro and undisputable antitumor efficacy in N2a-xenografted mice in vivo, compared to other tested sample groups (tumor volumes for PBS, BSA-Cur-NPs, free ICG, and ICG-BSA-Cur-NPs groups were 1408.6 ± 551.9, 1190.6 ± 343.6, 888.6 ± 566.2, and 103.0 ± 111.3 mm3, respectively).Conclusion: We demonstrate that these hyperthermal chemotherapeutic ICG-BSA-Cur-NPs have potential as a future brain tumor treatment.Keywords: indocyanine green, curcumin, photothermal therapy, albumin nanoparticles, tumor targeting