| Affiliation: | 1. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 P. R. China School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371 Singapore;2. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 P. R. China;3. State Key Laboratory of Nuclear Resources and Environment, East China University of Technology, Nanchang, 330013 P. R. China;4. Department of Periodontology, Stomatological Hospital, Jilin University, Changchun, 130021 P. R. China;5. Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, 12372 Saudi Arabia;6. School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371 Singapore |
| Abstract: | The outcome of laser-triggered plasmons-induced phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is significantly limited by the hypoxic tumor microenvironment and the upregulation of heat shock proteins (HSPs) in response to heat stress. Mitochondria, the biological battery of cells, can serve as an important breakthrough to overcome these obstacles. Herein, dendritic triangular pyramidal plasmonic CuPt alloys loaded with heat-sensitive NO donor N, N′-di-sec-butyl-N, N′-dinitroso-1,4-phenylenediamine (BNN) is developed. Under 808 nm laser irradiation, plasmonic CuPt can generate superoxide anion free radicals (·O2−) and heat simultaneously. The heat generated can then trigger the release of NO gas, which not only enables gas therapy but also damages the mitochondrial respiratory chain. Impaired mitochondrial respiration leads to reduced oxygen consumption and insufficient intracellular ATP supply, which effectively alleviates tumor hypoxia and undermines the synthesis of HSPs, in turn boosting plasmonic CuPt-based PDT and mild PTT. Additionally, the generated NO and ·O2− can react to form more cytotoxic peroxynitrite (ONOO−). This work describes a plasmonic CuPt@BNN (CPB) triggered closed-loop NO gas, free radicals, and mild photothermal therapy strategy that is highly effective at reciprocally promoting antitumor outcomes. |
