TY - JOUR
T1 - ROS-generating alginate-coated gold nanorods as biocompatible nanosonosensitisers for effective sonodynamic therapy of cancer
AU - Loke, Yean Leng
AU - Beishenaliev, Adilet
AU - Wang, Pei-Wen
AU - Lin, Chung Yin
AU - Chang, Chia Yu
AU - Foo, Yiing Yee
AU - Faruqu, Farid Nazer
AU - Leo, Bey Fen
AU - Misran, Misni
AU - Chung, Lip Yong
AU - Shieh, Dar Bin
AU - Kiew, Lik Voon
AU - Chang, Chia Ching
AU - Teo, Yin Yin
N1 - Funding Information:
This work was financially supported by The Ministry of Higher Education Malaysia through the Fundamental Research Grant Scheme (FRGS) (Grant number: FRGS/1/2019/STG01/UM/02/15). This work was also supported in part by the 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). The Center for Intelligent Drug Systems and Smart Biodevices (IDS 2 B) of NYCU and the Center of Applied Nanomedicine of NCKU supported this work from the Higher Education Sprout Project of the Taiwan Ministry of Education (MOE). Taiwan-Malaysia Semiconductor and Biomedical Oversea Science and Research Innovation Center, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, ROC.
Funding Information:
This work was financially supported by The Ministry of Higher Education Malaysia through the Fundamental Research Grant Scheme (FRGS) (Grant number: FRGS/1/2019/STG01/UM/02/15). This work was also supported in part by the 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). The Center for Intelligent Drug Systems and Smart Biodevices (IDS2B) of NYCU and the Center of Applied Nanomedicine of NCKU supported this work from the Higher Education Sprout Project of the Taiwan Ministry of Education (MOE). Taiwan-Malaysia Semiconductor and Biomedical Oversea Science and Research Innovation Center, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, ROC.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/6
Y1 - 2023/6
N2 - 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 (AuNRsALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRsALG 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 AuNRsALG 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. AuNRsALG 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 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.
AB - 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 (AuNRsALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRsALG 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 AuNRsALG 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. AuNRsALG 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 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.
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U2 - 10.1016/j.ultsonch.2023.106437
DO - 10.1016/j.ultsonch.2023.106437
M3 - Article
C2 - 37187119
AN - SCOPUS:85159231317
SN - 1350-4177
VL - 96
JO - Ultrasonics Sonochemistry
JF - Ultrasonics Sonochemistry
M1 - 106437
ER -
