ROS-generating alginate-coated gold nanorods as biocompatible nanosonosensitisers for effective sonodynamic therapy of cancer
Document Type
Article
Publication Date
6-1-2023
Abstract
Sonodynamic therapy (SDT) emerges as a promising non-invasive alternative for eradicating malignant tumours. However, its therapeutic efficacy remains limited due to the lack of sonosensitisers with high potency and biosafety. Previously, gold nanorods (AuNRs) have been extensively studied for their applications in photody-namic or photothermal cancer therapy, but their sonosensitising properties are largely unexplored. Here, we reported the applicability of alginate-coated AuNRs (AuNRsALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRsALG were found stable under ultrasound irradi-ation (1.0 W/cm(2), 5 min) and maintained structural integrity for 3 cycles of irradiation. The exposure of the AuNRsALG to ultrasound irradiation (1.0 W/cm(2), 5 min) was shown to enhance the cavitation effect significantly and generate a 3 to 8-fold higher amount of singlet oxygen (O-1(2)) than other reported commercial titanium di-oxide nanosonosensitisers. AuNRsALG exerted dose-dependent sonotoxicity on human MDA-MB-231 breast can-cer cells in vitro, with similar to 81% cancer cell killing efficacy at a sub-nanomolar level (IC50 was 0.68 nM) predominantly through apoptosis. The protein expression analysis showed significant DNA damage and down -regulation of anti-apoptotic Bcl-2, suggesting AuNRsALG induced cell death through the mitochondrial pathway. The addition of mannitol, a reactive oxygen species (ROS) scavenger, inhibited cancer-killing effect of AuNRsALG- mediated SDT, further verifying that the sonotoxicity of AuNRsALG is driven by the production of ROS. Overall, these results highlight the potential application of AuNRsALG as an effective nanosonosensitising agent in clinical settings.
Keywords
Gold nanorods (AuNRs), Sonodynamic therapy, Sonosensitiser, Singlet oxygen, Reactive oxygen species (ROS)
Divisions
molecular,sch_med,CHEMISTRY,nanotechnology,pharchemistry
Funders
Ministry of Higher Education Malaysia through the Fundamental Research Grant Scheme (FRGS) (Grant number: FRGS/1/2019/STG01/UM/02/15),National Science and Technology Council of Taiwan (Grant number: NSTC 111-2112-M -A49-025; 111-2321-B-A49-007; 111-2927-I-A49-004; 110-2314-B-006-117-MY3; 111-2320-B-006-042-MY3; 111-2218-E-006-019 and 110-2923-M-009-005-MY3),Higher Education Sprout Project of the Taiwan Ministry of Education (MOE),Taiwan-Malaysia Semiconductor,Biomedical Oversea Science and Research Innovation Center, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, ROC
Publication Title
Ultrasonics Sonochemistry
Volume
96
Publisher
Elsevier
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS