第5期雷万华等:光动力抗菌光敏剂的研究进展
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当BLRu与βEM-1Bla在37℃作用两小时,BLRu的发光强度提高了8倍,-内酰胺酶T说明B使发光的联吡啶钌结构脱落.同样,不存在βLRu能够有效地被TEM-1Bla水解,-内酰胺酶时,联吡啶钌光敏化产生单重态氧的过程也因与BHQ3之间的能量传递或而当联吡啶钌因βBHQ3对单重态氧分子的清除作用而受到抑制.-内酰胺酶的水解从
其产生单重态氧的能力将得到恢复.内源性βBLRu脱离后,-内酰胺酶是耐药菌对青霉素和头孢菌素等β它通过水解抗生素的β-内酰胺类抗生素产生耐药性的最主要机制,-内酰
胺结构使其丧失抑菌效力.因此,对β-内酰胺酶的检测识别有助于指导抗生素在临床上的有效治疗,同时β利用BLRu-内酰胺酶也成为对耐药菌实现有效灭活的一个重要靶点.对β有效产生单重态氧的特性,可能实现对不同β-内酰胺酶响应后发光增强、-内酰胺酶表达水平的细菌的特异性识别成像及选择性光动力杀伤.在激光共聚焦显微成像实验中,将B发现大量表达βLRu与几种不同的细菌培养后观察其发光情况,-内酰胺酶的青霉
和两种耐甲氧西林金黄色葡萄球菌株(素G耐药蜡样芽孢杆菌(B.cereus)MRSA,)有很强的发光;而βBAA39和BAA44-内酰胺酶无显著表达的甲氧西林敏感金黄色葡萄
),)球菌(和大肠杆菌(却观察不到明显的发光.同样,在BS.aureusE.coliDH5LRu对α
、上述几种细菌的光动力杀伤实验中,BLRu对B.cereusBAA39和BAA44具有很强的光动力抗菌活性,但对S.对E.aureus的光动力抗菌活性较弱,coli则基本无光动力抗这些结果表明,此类结构的钌配合物具有很大的潜力成为显微成像技术结合光菌活性.
动力抗菌治疗的多功能药物.
如上所述,近年来出现了许多结构新颖、灭菌活性优异的光敏剂药物体系.然而对于他们P动物模型体内实验研究还亟待开展.ACT活性的研究主要还处于细胞实验水平,此外,如何提高光敏药物体系对细菌的选择性杀伤能力,也是有待深入探讨的一个问题.可以预见,随着更多更好的新型光敏剂的开发,以及光源、光输送等技术的不断发展,PACT在治疗病原微生物感染疾病领域的应用将会越来越广.参考文献:
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ResearchProressofPhotodnamicAntimicrobialPhotosensitizers gy
,WANLEIWanhuaGXueson - -g
(KeLaboratoroPhotochemicalConversionand Otoelectronic Materials, y yf p
TechnicalInstituteoPhsicsand ChemistrChineseAcademoSciences,Beiin00190,P.R,China) f yy,yf jg1
:AbstractPhotodnamicantimicrobialchemotheraPACT)isanewteofantimicrobial ypy(yp,)usinreactiveoxensecies(ROSeneratedbaphotosensitizerandvisiblelihtaroach gygpgygpp
,killathoenicmicrooranisms.ROScanreactwithmostbioloicalcomonentsofbacteriato pgggpmakintheacuiredresistancetoPACTunlikel.Thisisthemainimetusforrecent gqyp attentionnACT.Thiseviewummarizesecentevelomentsfewincreasin o P r s r d o npg ,i,bncludinerivativesoronirrometheneomoundshotosensitizersorhrin d d cgpypppy p
(,(),BODIPY)conuatedandRuIIcomlexesforPACTalicaolelectroltesolridl -jgppppyypypyytions.
:;;Kewordshotodnamicantimicrobialchemotherahotosensitizerantibioticresistance -pypypy
:WANG,:CorresondinauthorXuesonE-mailxswanail.ic.ac.cn. -@mpgggp