Intelligent Bimetallic Nanoagents as Reactive Oxygen Species Initiator System for Effective Combination Phototherapy

Hongfeng Li; Ying Li; Jingjing Xiang; Xing Yang; Chunbing Li; Chuangjun Liu; Qi Zhao; Lihua Zhou; Ping Gong; Jiahao Huang

doi:10.3389/fbioe.2020.00423

Intelligent Bimetallic Nanoagents as Reactive Oxygen Species Initiator System for Effective Combination Phototherapy

Front Bioeng Biotechnol. 2020 May 8:8:423. doi: 10.3389/fbioe.2020.00423. eCollection 2020.

Authors

Hongfeng Li^{1

2}, Ying Li^{2

3}, Jingjing Xiang^{2

4}, Xing Yang^{2

4}, Chunbing Li², Chuangjun Liu², Qi Zhao⁵, Lihua Zhou², Ping Gong^{2

6}, Jiahao Huang¹

Affiliations

¹ Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, China.
² Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, China.
³ School of Materials Science and Engineering, Guilin University of Electronic Technology, Guilin, China.
⁴ University of Chinese Academy of Sciences, Beijing, China.
⁵ Faculty of Health Sciences, University of Macau, Macau, China.
⁶ Dongguan Key Laboratory of Drug Design and Formulation Technology, Key Laboratory for Nanomedicine, Guangdong Medical University, Dongguan, China.

Abstract

Phototherapy is a promising oncotherapy method. However, there are various factors greatly restricted phototherapy development, including poor tumor-specific accumulation, the hypoxia in solid tumor, and the systemic phototoxicity of photosensitizer. Herein, a tumor microenvironment (TME)-responsive intelligent bimetallic nanoagents (HSA-Pd-Fe-Ce6 NAs) composed of human serum albumin (HSA), palladium-iron (Pd-Fe) bimetallic particles, and chlorin e6 (Ce6) was designed for effective combination phototherapy. The Pd-Fe part in the HSA-Pd-Fe-Ce6 NAs would react with the endogenous hydrogen peroxide (H₂O₂) in an acidic ambiance within tumor to generate cytotoxic superoxide anion free radical through the "Fenton-like reaction." H₂O₂, coupled with highly toxic singlet oxygen (¹O₂) caused by the Ce6 component under the irradiation of 660 nm laser, resulted in synergistic cancer therapy effects in hypoxia surroundings. Besides, this nanoagents could result in hyperpyrexia-induced cell apoptosis because of superior absorption performance in near-infrared wavelength window bringing about excellent photothermal conversion efficiency. The cell cytotoxicity results showed that the survival rate after treated by 40 μg mL^-1 nanoagents was only 17%, which reveals that the HSA-Pd-Fe-Ce6 NAs had the advantage of efficient and controllable phototherapy. In short, it exhibited excellent hypoxia-resistant combination phototherapy efficacy in vitro. Therefore, the multifunctional nanoagents are powerful and provide a new avenue for effective combination phototherapy.

Keywords: bimetallic nanoagents; photosensitizers; phototherapy; reactive oxygen species; tumor microenvironment.