ROS-generating alginate-coated gold nanorods as biocompatible nanosonosensitisers for effective sonodynamic therapy of cancer

Yean Leng Loke; Adilet Beishenaliev; Pei-Wen Wang; Chung-Yin Lin; Chia-Yu Chang; Yiing Yee Foo; Farid Nazer Faruqu; Bey Fen Leo; Misni Misran; Lip Yong Chung; Dar-Bin Shieh; Lik Voon Kiew; Chia-Ching Chang; Yin Yin Teo

doi:10.1016/j.ultsonch.2023.106437

ROS-generating alginate-coated gold nanorods as biocompatible nanosonosensitisers for effective sonodynamic therapy of cancer

Ultrason Sonochem. 2023 Jun:96:106437. doi: 10.1016/j.ultsonch.2023.106437. Epub 2023 May 8.

Authors

Affiliations

¹ Department of Chemistry, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
² Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
³ Institute of Oral Medicine and School of Dentistry, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 70101 Tainan, Taiwan; Center of Applied Nanomedicine, National Cheng Kung University, 70101 Tainan, Taiwan.
⁴ Institute for Radiological Research, Chang Gung University, 33303 Taoyuan, Taiwan; Department of Neurology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 33303 Taoyuan, Taiwan.
⁵ Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan; Center for Intelligent Drug Systems and Smart Bio-devices (IDS(2)B), National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan.
⁶ Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia; Nanotechnology & Catalysis Research Centre (NANOCAT), Institute for Advanced Studies, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
⁷ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
⁸ Institute of Oral Medicine and School of Dentistry, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 70101 Tainan, Taiwan; Center of Applied Nanomedicine, National Cheng Kung University, 70101 Tainan, Taiwan; Department of Stomatology, National Cheng Kung University Hospital, 70403 Tainan, Taiwan.
⁹ Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan. Electronic address: lvkiew@um.edu.my.
¹⁰ Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan; Center for Intelligent Drug Systems and Smart Bio-devices (IDS(2)B), National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan; Department of Electrophysics, National Yang Ming Chiao Tung University, 30010 Hsinchu, Taiwan; Institute of Physics, Academia Sinica, Nankang, 11529 Taipei, Taiwan; Brain Research Center, National Tsing Hua University, 300044 Hsinchu, Taiwan, ROC. Electronic address: ccchang01@nycu.edu.tw.
¹¹ Department of Chemistry, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: yinyinteo@um.edu.my.

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 photodynamic or photothermal cancer therapy, but their sonosensitising properties are largely unexplored. Here, we reported the applicability of alginate-coated AuNRs (AuNRs^ALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRs^ALG were found stable under ultrasound irradiation (1.0 W/cm², 5 min) and maintained structural integrity for 3 cycles of irradiation. The exposure of the AuNRs^ALG to ultrasound irradiation (1.0 W/cm², 5 min) was shown to enhance the cavitation effect significantly and generate a 3 to 8-fold higher amount of singlet oxygen (¹O₂) than other reported commercial titanium dioxide nanosonosensitisers. AuNRs^ALG exerted dose-dependent sonotoxicity on human MDA-MB-231 breast cancer cells in vitro, with ∼ 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 downregulation of anti-apoptotic Bcl-2, suggesting AuNRs^ALG induced cell death through the mitochondrial pathway. The addition of mannitol, a reactive oxygen species (ROS) scavenger, inhibited cancer-killing effect of AuNRs^ALG-mediated SDT, further verifying that the sonotoxicity of AuNRs^ALG is driven by the production of ROS. Overall, these results highlight the potential application of AuNRs^ALG as an effective nanosonosensitising agent in clinical settings.

Keywords: Gold nanorods (AuNRs); Reactive oxygen species (ROS); Singlet oxygen; Sonodynamic therapy; Sonosensitiser.

MeSH terms

Alginates
Cell Line, Tumor
Gold / chemistry
Gold / pharmacology
Humans
Nanotubes* / chemistry
Neoplasms* / drug therapy
Reactive Oxygen Species / metabolism

Substances

Reactive Oxygen Species
Alginates
Gold