7 results on '"Kiew, Lik Voon"'
Search Results
2. Near-infrared activatable phthalocyanine-poly-L-glutamic acid conjugate: increased cellular uptake and light–dark toxicity ratio toward an effective photodynamic cancer therapy.
- Author
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Kiew, Lik Voon, Cheah, Hoay Yan, Voon, Siew Hui, Gallon, Elena, Movellan, Julie, Ng, Kia Hui, Alpugan, Serkan, Lee, Hong Boon, Dumoulin, Fabienne, Vicent, María J., and Chung, Lip Yong
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PHOTODYNAMIC therapy ,BREAST cancer treatment ,ZINC phthalocyanine ,ENDOCYTOSIS ,REACTIVE oxygen species ,PHOTOSENSITIZERS ,THERAPEUTICS - Abstract
In photodynamic therapy (PDT), the low absorptivity of photosensitizers in an aqueous environment reduces singlet oxygen generation efficiency and thereby decreases photosensitizing efficacy in biological conditions. To circumvent this problem, we designed a phthalocyanine-poly-L-glutamic acid conjugate ( 1-PG ) made from a new phthalocyanine ( Pc 1 ) monofunctionalized to allow adequate conjugation to PGA. The resulting 1-PG conjugate retained high absorptivity in the near-infrared (NIR) region at its λ max 675 nm in an aqueous environment. The 1-PG conjugate demonstrated good singlet oxygen generation efficiency, increased uptake by 4 T1 breast cancer cells via clathrin-mediated endocytosis, and enhanced photocytotoxic efficacy. The conjugate also displayed a high light–dark toxicity ratio, approximately 1.5-fold greater than zinc phthalocyanine at higher concentration (10 μM), an important feature for the reduction of dark toxicity and unwanted side effects. These results suggest that the 1-PG conjugate could be a useful alternative for deep tissue treatment with enhanced anti-cancer (PDT) efficacy. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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3. Improved Photodynamic Efficacy of Zn(II) Phthalocyanines via Glycerol Substitution.
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Chin, Yunni, Lim, Siang Hui, Zorlu, Yunus, Ahsen, Vefa, Kiew, Lik Voon, Chung, Lip Yong, Dumoulin, Fabienne, and Lee, Hong Boon
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PHOTODYNAMIC therapy ,ZINC phthalocyanine ,GLYCERIN ,PHOTOSENSITIZERS ,SOLUBILITY ,REACTIVE oxygen species ,CANCER cell culture - Abstract
Phthalocyanines are excellent photosensitizers for photodynamic therapy as they have strong absorbance in the near infra-red region which is most relevant for in vivo activation in deeper tissular regions. However, most phthalocyanines present two major challenges, ie, a strong tendency to aggregate and low water-solubility, limiting their effective usage clinically. In the present study, we evaluated the potential enhancement capability of glycerol substitution on the photodynamic properties of zinc (II) phthalocyanines (ZnPc). Three glycerol substituted ZnPc, 1–3, (tetra peripherally, tetra non-peripherally and mono iodinated tri non-peripherally respectively) were evaluated in terms of their spectroscopic properties, rate of singlet oxygen generation, partition coefficient (log P), intracellular uptake, photo-induced cytotoxicity and vascular occlusion efficiency. Tetrasulfonated ZnPc (ZnPcS
4 ) was included as a reference compound. Here, we showed that 1–3 exhibited 10–100 nm red-shifted absorption peaks with higher molar absorptivity, and at least two-fold greater singlet oxygen generation rates compared to ZnPcS4 . Meanwhile, phthalocyanines 1 and 2 showed more hydrophilic log P values than 3 consistent with the number of glycerol attachments but 3 was most readily taken up by cells compared to the rest. Both phthalocyanines 2 and 3 exhibited potent phototoxicity against MCF-7, HCT-116 and HSC-2 cancer cell-lines with IC50 ranging 2.8–3.2 µM and 0.04–0.06 µM respectively, while 1 and ZnPcS4 (up to 100 µM) failed to yield determinable IC50 values. In terms of vascular occlusion efficiency, phthalocyanine 3 showed better effects than 2 by causing total occlusion of vessels with diameter <70 µm of the chorioallantoic membrane. Meanwhile, no detectable vascular occlusion was observed for ZnPcS4 with treatment under similar experimental conditions. These findings provide evidence that glycerol substitution, in particular in structures 2 and 3, is able to improve the photodynamic properties of ZnPc. [ABSTRACT FROM AUTHOR]- Published
- 2014
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4. Ruthenium(II) polypyridyl complexes as emerging photosensitisers for antibacterial photodynamic therapy.
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Ng, Xiao Ying, Fong, Kar Wai, Kiew, Lik Voon, Chung, Pooi Yin, Liew, Yun Khoon, Delsuc, Nicolas, Zulkefeli, Mohd, and Low, May Lee
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PHOTODYNAMIC therapy , *REACTIVE oxygen species , *RUTHENIUM , *ACOUSTIC imaging , *METALS in medicine , *PHOTOTHERMAL effect - Abstract
Photodynamic therapy (PDT) has recently emerged as a potential valuable alternative to treat microbial infections. In PDT, singlet oxygen is generated in the presence of photosensitisers and oxygen under light irradiation of a specific wavelength, causing cytotoxic damage to bacteria. This review highlights different generations of photosensitisers and the common characteristics of ideal photosensitisers. It also focuses on the emergence of ruthenium and more specifically on Ru(II) polypyridyl complexes as metal-based photosensitisers used in antimicrobial photodynamic therapy (aPDT). Their photochemical and photophysical properties as well as structures are discussed while relating them to their phototoxicity. The use of Ru(II) complexes with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy to improve on previous shortcomings of the complexes are outlined. Future perspectives of these complexes used in two-photon PDT, photoacoustic imaging and sonotherapy are also discussed. This review covers the literature published from 2017 to 2023. The review discussed the use of Ru(II) polypyridyl complexes with structural modifications as antibacterial photodynamic therapy agents together with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy. The possible use of Ru(II) complexes in two-photon photodynamic therapy, photoacoustic imaging and sonotherapy in the future was also discussed. [Display omitted] • Antibacterial studies of Ru(II) photosensitisers with structural modifications. • Advancements in strategies - nanoformulations, combinatory and photothermal therapies. • Future use - two-photon photodynamic therapy, photoacoustic imaging and sonotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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5. ROS-generating alginate-coated gold nanorods as biocompatible nanosonosensitisers for effective sonodynamic therapy of cancer.
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Loke, Yean Leng, Beishenaliev, Adilet, Wang, Pei-Wen, Lin, Chung-Yin, Chang, Chia-Yu, Foo, Yiing Yee, Faruqu, Farid Nazer, Leo, Bey Fen, Misran, Misni, Chung, Lip Yong, Shieh, Dar-Bin, Kiew, Lik Voon, Chang, Chia-Ching, and Teo, Yin Yin
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MANNITOL , *NANORODS , *CANCER treatment , *REACTIVE oxygen species , *CANCER cells , *GOLD , *DNA damage , *BCL genes - Abstract
• Development of AuNRsALG nanosonosensitisers for enhanced SDT of breast cancer. • AuNRsALG showed good biocompatibility and sono-stability. • AuNRsALG produced •OH &1O 2 more effectively than the commercial sonosensitisers. • AuNRsALG exhibited high sonotoxicity in breast cancer cells at nanomolar range. • AuNRsALG induced severe DNA damage and cell apoptosis via mitochondrial pathway. 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 (1O 2) 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 (IC 50 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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6. Facile synthesis of biocompatible sub-5 nm alginate-stabilised gold nanoparticles with sonosensitising properties.
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Beishenaliev, Adilet, Faruqu, Farid Nazer, Leo, Bey Fen, Lit, Lei Cheng, Loke, Yean Leng, Chang, Chia-Ching, Teo, Yin Yin, Chik, Zamri, Foo, Yiing Yee, Chung, Lip Yong, and Kiew, Lik Voon
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GOLD nanoparticles , *SODIUM alginate , *REACTIVE oxygen species , *BREAST cancer , *ULTRASONIC imaging , *ZETA potential - Abstract
The use of ultrasmall gold nanoparticles (usAuNPs, diameters <5 nm) in cancer diagnosis and therapy has been increasing due to their unique tumour tissue/cell penetrating traits and renal-excretable properties. In order to produce usAuNPs with narrow polydispersity, toxic stabilising agents were normally coated on usAuNP surface during their synthesis. This has necessitated post-synthesis surface modification to minimise stabilising-agent-related toxicity in order to qualify usAuNPs for in vivo use. Nevertheless, the average sizes of usAuNPs that were surface-modified using the reported methods were often found to be above the renal filtration threshold (5 nm), hence limiting their renal excretion and suitability for in vivo use. Here, we report a novel and facile synthesis of biocompatible and renal-clearable usAuNPs using sodium alginate as the stabilising agent. The alginate-stabilised usAuNPs (usAuNPsALG) had an average size of 4.5 ± 0.2 nm with narrow polydispersity (0.21), a zeta potential of −30.4 mV, and were stable in water for up to 45 days. They were haemocompatible and non-toxic in vitro at concentrations up to 100 μg/ml (4T1 breast cancer cells). Further, usAuNPsALG were found to generate reactive oxygen species and exert dose-dependent sonotoxicity to 4T1 and MDA-MB-231 cells in vitro at a level equivalent to that of the larger AuNPs (>5 nm), but upon ultrasound irradiation at 2–4-fold lower frequency (1 MHz) and intensity (0.5 W/cm2) than those previously reported in AuNP-mediated SDT. This suggests the potential use of the usAuNPsALG as sonosensitising agents for anti-cancer adjunctive therapy. Overall, this study reported the novel method for the synthesis of biocompatible usAuNPs with considerable sonosensitising properties and the potential of these sub-5 nm nanoparticles for in vivo applications. [Display omitted] • Facile synthesis of ultrasmall gold nanoparticles (<5 nm) with alginate (usAuNPsALG). • usAuNPsALG showed improved haemo- and cytocompatibility as compared to conventional usAuNPsCTAB. • usAuNPsALG exerted dose-dependent in vitro sonotoxicity to 4T1 and MDA-MB-231 cells. • Sonotoxicity by usAuNPsALG was comparable to larger AuNPs but achieved at lower ultrasound frequency and intensity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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7. Active targeted ligand-aza-BODIPY conjugate for near-infrared photodynamic therapy in melanoma.
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Ng, Shie Yin, Kamkaew, Anyanee, Fu, Nanyan, Kue, Chin Siang, Chung, Lip Yong, Kiew, Lik Voon, Wittayakun, Jatuporn, Burgess, Kevin, and Lee, Hong Boon
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PHOTODYNAMIC therapy , *ENDOCYTOSIS , *MELANOMA , *REACTIVE oxygen species , *TUMORS , *PHOTOSENSITIZERS , *MELANINS - Abstract
• Active targeted aza-BODIPY conjugates are promising photosensitizers for melanoma. • Ex vivo biodistribution assay showed conjugates 1a and 1b accumulated in the tumour. • 1b was found to reduce tumour volume and growth suppression after PDT up to 12 days. Active targeting compound, a non-iodinated derivative of IK-IK-I 2 -azaBODIPY (1a) was previously reported to preferentially bind melanoma over healthy cells. In this study, we evaluate the photodynamic therapy (PDT) efficiency on melanoma cells of 1a , together with its reversed sequence compound KI-KI-I 2 -azaBODIPY (1b) and a non-targeted control I 2 -azaBODIPY-NH 2 (2). All three test compounds possess absorption wavelengths in the near-infrared (NIR) region (λ max between 678 and 687 nm) which alleviate melanin interference and allow deeper tissue penetration. In vitro studies revealed 1a and 1b are promising photosensitizers with enhanced singlet oxygen generation, have increased uptake by B16-F10 melanoma cells via clathrin-mediated endocytosis and good photocytotoxic efficacies. Ex vivo biodistribution assays showed both 1a and 1 b accumulated in the tumour. In B16-F10 tumour bearing-C57BL/6 mice, 10 mg/kg of 1b and light irradiation was found to reduce tumour volume by up to 23% at day-3. Doubling the dosage of 1b (20 mg/kg) enhanced the antitumour effect, showing 96% maximum tumour volume reduction at day-7 and tumour growth suppression for up to 12 days. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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