ORCID Profile
0000-0001-7131-1154
Current Organisation
Sun Yat-Sen University
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Publisher: Wiley
Date: 26-11-2018
Abstract: Emerging studies have shown that mitochondrial DNA (mtDNA) is an attractive target for anticancer therapeutics. Herein, a heterobimetallic complex [Ru(dip) 2 (μ‐bpm)PtCl 2 ]Cl 2 ( RuPt dip=4,7‐diphenyl‐1,10‐phenanthroline bpm=2,2′‐bipyrimidine) and the corresponding mononuclear complex [Ru(dip) 2 (bpm)]Cl 2 ( Ru ) have been designed and synthesized. RuPt can bind to mtDNA and damage it both in the dark and upon visible light irradiation. By using a variety of methods, it was demonstrated that RuPt can interfere with the function of mtDNA by decreasing the lification and copy number of mtDNA, and affecting the transcriptional level of mitochondria‐encoded genes. Furthermore, RuPt can disturb the physiological processes of mitochondria and induce caspase‐dependent apoptosis in the presence of light. In addition, RuPt shows low systemic toxicity and potent in vivo anticancer potency upon light irradiation. This study provides strong evidence that mtDNA is an important molecular target of RuPt , and photodamaging mtDNA is an effective strategy to overcome cisplatin resistance.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NR00377C
Abstract: Drug to carrier ratio is an important consideration in designing drug platforms, since a low loading capacity necessitates the use of high doses of carriers, which can result in side effects. Here, we have engineered a platform to co-deliver small molecule drugs and small interfering RNA (siRNA). This platform consists of cyclodextrin-grafted polyethylenimine (CP) functionalized mesoporous silica nanoparticles (MSNP). A unique multi-step encapsulation procedure was used to obtain a high loading capacity for doxorubicin (DOX) and siRNA oligos specific for the PKM2 gene that encodes pyruvate kinase M2, an enzyme catalyzing the final rate-limiting step in glycolysis. We systematically characterized this platform (CP-MSNP@DOX/PKM2) in vitro and evaluated its therapeutic efficacy in vivo with a mouse model of triple negative breast cancer (TNBC). Exposure of TNBC cells to CP-MSNP@DOX/PKM2 resulted in suppressed target gene expression, reduced cell proliferation, and enhanced apoptosis. Intravenous administration of the drug substantially decreased the tumor burden in comparison to DOX or siRNA monotherapy. In conclusion, we have developed a platform for efficient co-delivery of small molecule drugs and therapeutic siRNA.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6SC02901A
Abstract: We report a rational design and mechanism studies of mitochondria-immobilized iridium( iii ) complexes that can kill cancer cells by targeting mitochondrial metabolism.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7DT02477K
Abstract: In this work, three iridium( iii ) complexes were investigated as combined photodynamic and photoactivated chemotherapeutic agents.
Publisher: American Chemical Society (ACS)
Date: 21-04-2017
Publisher: American Chemical Society (ACS)
Date: 24-07-2023
Publisher: Wiley
Date: 04-2014
Publisher: Ivyspring International Publisher
Date: 2014
DOI: 10.7150/THNO.8263
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5SC01955A
Abstract: We report the rational design and photodynamic anticancer mechanism studies of iridium( iii ) complexes with pH-responsive singlet oxygen ( 1 O 2 ) production and lysosome-specific imaging properties.
Publisher: American Chemical Society (ACS)
Date: 18-10-2013
DOI: 10.1021/NN4035316
Publisher: American Chemical Society (ACS)
Date: 06-04-2017
Abstract: Phosphorescent Ir(III) complexes are expected to be new multifunctional theranostic platforms that enable the integration of imaging capabilities and anticancer properties. Mitophagy is an important selective autophagic process that degrades dysfunctional mitochondria. Until now, the regulation of mitophagy is still poorly understood. Herein, we present two phosphorescent cyclometalated iridium(III) complexes (Ir1 and Ir2) that can accumulate in mitochondria and induce mitophagy. Because of their intrinsic phosphorescence, they can specially image mitochondria and track mitochondrial morphological alterations. Mechanism studies show that Ir1 and Ir2 induce mitophagy by depolarization of mitochondrial membrane potential, depletion of cellular ATP, perturbation in mitochondrial metabolic status, and induction of oxidative stress. Moreover, no sign of apoptosis is observed in Ir1- and Ir2-treated cells under the same conditions that an obvious mitophagic response is initiated. We demonstrate that Ir1 is a promising theranostic agent that can induce mitophagy and visualize changes in mitochondrial morphology simultaneously.
Publisher: MyJove Corporation
Date: 15-01-2015
DOI: 10.3791/52075
Publisher: Wiley
Date: 26-04-2019
Abstract: The chemo-anti-inflammatory strategy is attracting ever more attention for the treatment of cancer. Here, two cyclometalated Ir
Publisher: American Chemical Society (ACS)
Date: 28-02-2019
DOI: 10.1021/ACS.JMEDCHEM.8B01704
Abstract: Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir(III) complexes Ir1-Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1-Ir6 show much higher cytotoxicity than cisplatin and they can effectively localize to mitochondria. Among them, complexes Ir3 and Ir4 with dipyrido[3,2- a:2',3'- c]phenazine (dppz) ligands can bind to DNA tightly in vitro, intercalate to mtDNA in situ, and induce mtDNA damage. Ir3- and Ir4-impaired mitochondria exhibit decline of mitochondrial membrane potential, disability of adenosine triphosphate generation, disruption of mitochondrial energetic and metabolic status, which subsequently cause protective mitophagy, G
Publisher: Wiley
Date: 09-10-2017
Abstract: Valproic acid (VPA) is a short-chain, fatty acid type histone deacetylase inhibitor (HDACi), which can cause growth arrest and induce differentiation of transformed cells. Phosphorescent cyclometalated Ir
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8DT00783G
Abstract: A potent anticancer Ir( iii ) complex induces paraptotic cell death by causing mitochondrial dysfunction rapidly and inhibits tumor growth significantly in vivo .
No related grants have been discovered for Zong-Wan Mao.