光动力抗菌光敏剂的研究进展

doi:10.7517/j.issn.1674-0475.2013.05.321

摘要/Abstract

摘要：

光动力抗菌化学疗法是一种结合光敏剂分子和可见光产生的活性氧物种杀灭病原微生物的抗感染治疗方法.活性氧物种能够与致病菌中的多种生物活性分子反应,这一特性使得微生物不易对该方法产生耐药性,这也是该方法近年来备受关注的主要原因.本文重点介绍了近年来光动力抗菌化学疗法领域新型光敏剂药物的研究进展,包括卟啉类衍生物、BODIPY化合物、共轭聚合物和钌多吡啶配合物.

关键词: 光动力抗菌化学疗法, 光敏剂, 抗生素耐药

Abstract:

Photodynamic antimicrobial chemotherapy (PACT) is a new type of antimicrobial approach, using reactive oxygen species (ROS) generated by a photosensitizer and visible light to kill pathogenic microorganisms. ROS can react with most biological components of bacteria, making the acquired resistance to PACT unlikely. This is the main impetus for recent increasing attention on PACT. This review summarizes recent developments of new photosensitizers, including porphyrin derivatives, boron dipyrromethene compounds (BODIPY), conjugated polyelectrolytes and Ru(II) polypyridyl complexes, for PACT applications.

Key words: photodynamic antimicrobial chemotherapy, photosensitizer, antibiotic-resistance

中图分类号:

雷万华, 王雪松. 光动力抗菌光敏剂的研究进展[J]. 影像科学与光化学, 2013, 31(5): 321-334.

LEI Wan-hua, WANG Xue-song. Research Progress of Photodynamic Antimicrobial Photosensitizers[J]. Imaging Science and Photochemistry, 2013, 31(5): 321-334.

参考文献

[1] (a) Wainwright M. Photodynamic antimicrobial chemotherapy (PACT)[J]. Journal of Antimicrobial Chemotherapy, 1998, 42(1): 13-28. (b) Hamblin M R, Hasan T. Photodynamic therapy: a new antimicrobial approach to infectious disease? [J].Photochemical & Photobiological Sciences, 2004, 3(5): 436-450. (c) Jori G, Coppellotti O. Inactivation of pathogenic microorganisms by photodynamic techniques: mechanistic aspects and perspective applications[J]. Anti-Infective Agents in Medicinal Chemistry, 2007, 6(2): 119-131. (d) Maisch T. Revitalized strategies against multi-resistant bacteria: antimicrobial photodynamic therapy and bacteriophage therapy[J]. Anti-Infective Agents in Medicinal Chemistry, 2007, 6(2): 145-150.

[2] Wainwright M. The emerging chemistry of blood product disinfection[J]. Chemical Society Reviews, 2002, 31(2): 128-136.

[3] (a) Wilson M. Photolysis of oral bacteria and its potential use in the treatment of caries and periodontal disease[J]. Journal of Applied Bacteriology, 1993, 75(4): 299-306. (b) Wilson M. Lethal photosensitisation of oral bacteria and its potential application in the photodynamic therapy of oral infections[J]. Photochemical & Photobiological Sciences, 2004, 3(5): 412-418.

[4] Noimark S, Dunnill C W, Wilson M, et al. The role of surfaces in catheter-associated infections[J]. Chemical Society Reviews, 2009, 38(12): 3435-3448.

[5] Korytowski W, Bachowski G J, Girotti A W. Photoperoxidation of cholesterol in homogeneous solution, isolated membranes, and cells: comparison of the 5α- and 6β-hydroperoxides as indicators of singlet oxygen intermediacy[J]. Photochemistry and Photobiology, 1992, 56(1): 1-8.

[6] Girotti A W. Photodynamic lipid peroxidation in biological systems[J].Photochemistry and Photobiology, 1990, 51(4): 497-509.

[7] (a) Vaara M, Vaara T. Polycations as outer membrane-disorganizing agents[J]. Antimicrobial Agents and Chemotherapy, 1983, 24(1): 114-122. (b) Bertolini G, Rossi F, Valduga G, et al. Photosensitizing activity of water- and lipid-soluble phthalocyanines on Escherichia coli[J]. FEMS Microbiology Letters, 1990, 71(1-2): 149-155. (c) Nitzan Y, Gutterman M, Malik Z, et al. Inactivation of gram-negative bacteria by photosensitized porphyrins[J]. Photochemistry and Photobiology, 1992, 55(1): 89-96.

[8] (a) Reddi E, Ceccon M, Valduga G, et al. Photophysical properties and antibacterial activity of meso-substituted cationic porphyrins[J]. Photochemistry and Photobiology, 2002, 75(5): 462-470. (b) Rovaldi C R, Piecsky A, Sole N A, et al. Photoactive porphyrin derivative with broad spectrum activity against oral pathogens in vitro[J]. Antimicrobial Agents and Chemotherapy, 2000, 44(12): 3364-3367. (c) Sol V, Branland P, Chaleix V, et al. Amino porphyrins as photoinhibitors of Gram-positive and -negative bacteria[J]. Bioorganic & Medicinal Chemistry Letters, 2004, 14(16): 4207-4211. (d) Dosselli R, Gobbo M, Bolognini E, et al. Porphyrin apidaecin conjugate as a new broad spectrum antibacterial agent[J]. ACS Medicinal Chemistry Letters, 2010, 1(1): 35-38. (e) Choi K H, Lee H J, Park B J, et al. Photosensitizer and vancomycin-conjugated novel multifunctional magnetic particles as photoinactivation agents for selective killing of pathogenic bacteria[J]. Chemical Communications, 2012, 48(38): 4591-4593.

[9] (a) Zolfaghari P S, Packer S, Singer M, et al. In vivo killing of Staphylococcus aureus using a light-activated antimicrobial agent[J]. BMC Microbiology, 2009, 9: 27. (b) Wilson M, Dobson J, Harvey W. Sensitization of oral bacteria to killing by low-power laser radiation[J]. Current Microbiology, 1992, 25(2): 77-81. (c) Wong T W, Wang Y Y, Sheu H M, et al. Bactericidal effects of toluidine blue-mediated photodynamic action on Vibrio vulnificus[J]. Antimicrobial Agents and Chemotherapy, 2005, 49(3): 895-902.

[10] Xing C F, Xu Q L, Tang H W, et al. Conjugated polymer/porphyrin complexes for efficient energy transfer and improving light-activated antibacterial activity[J]. Journal of the American Chemical Society, 2009, 131(36): 13117-13124.

[11] Strassert C A, Otter M, Albuquerque R Q, et al. Photoactive hybrid nanomaterial for targeting, labeling, and killing antibiotic-resistant bacteria[J]. Angewandte Chemie International Edition, 2009, 48(42): 7928-7931.

[12] Carvalho C M B, Alves E, Costa L, et al. Functional cationic nanomagnet-porphyrin hybrids for the photoinactivation of microorganisms[J]. ACS Nano, 2010, 4(12): 7133-7140.

[13] Jiang G, Lei W, Hou Y, et al. Photodynamic inactivation of Escherichia coli by porphyrin cytochrome c[J]. New Journal of Chemistry, 2012, 36(11): 2180-2183.

[14] (a) Loudet A, Burgess K. BODIPY dyes and their derivatives: syntheses and spectroscopic properties[J]. Chemical Reviews, 2007, 107(11): 4891-4932. (b) Ulrich G, Ziessel R, Harriman A. The chemistry of fluorescent bodipy dyes: versatility unsurpassed[J]. Angewandte Chemie International Edition, 2008,47(7): 1184-1201.

[15] (a) Killoran J, Allen L, Gallagher J F, et al. Synthesis of BF₂ chelates of tetraarylazadipyrromethenes and evidence for their photodynamic therapeutic behavior[J]. Chemical Communications, 2002, 38(17): 1862-1863. (b) Gorman A, Killoran J, O'Shea C, et al. In vitro demonstration of the heavy-atom effect for photodynamic therapy[J]. Journal of the American Chemical Society, 2004, 126(34): 10619-10631. (c) He H, Lo P C, Yeung S L, et al. Chemical Communications, 2011, 47(16): 4748-4750.

[16] Caruso E, Banfi S, Barbieri P, et al. Synthesis and antibacterial activity of novel cationic BODIPY photosensitizers[J]. Journal of Photochemistry and Photobiology B: Biology, 2012, 114: 44-51.

[17] (a) Gallagher W M, Allen L T, O'Shea C, et al. A potent nonporphyrin class of photodynamic therapeutic agent: cellular localisation, cytotoxic potential and influence of hypoxia[J]. British Journal of Cancer, 2005, 92(9): 1702-1710. (b) Byrne A T, O' Connor A, Hall M, et al. Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment[J]. British Journal of Cancer, 2009, 101(9): 1565-1573.

[18] Frimannsson D O, Grossi M, Murtagh J, et al. Light induced antimicrobial properties of a brominated boron difluoride (BF₂) chelated tetraarylazadipyrromethene photosensitizer[J]. Journal of Medicinal Chemistry, 2010, 53(20): 7337-7343.

[19] Wang Y, Chi E Y, Schanze K S, et al. Membrane activity of antimicrobial phenylene ethynylene based polymers and oligomers[J]. Soft Matter, 2012, 8(33): 8547-8558.

[20] (a) McQuade D T, Pullen A E, Swager T M. Conjugated polymer-based chemical sensors[J]. Chemical Reviews, 2000, 100(7): 2537-2574. (b) Jiang H, Zhao X, Shelton A H, et al. Variable-band-gap poly(arylene ethynylene) conjugated polyelectrolytes adsorbed on nanocrystalline TiO₂: photocurrent efficiency as a function of the band gap[J]. ACS Applied Materials & Interfaces, 2009, 1(2): 381-387. (c) Taranekar P, Qiao Q, Jiang H, et al. Hyperbranched conjugated polyelectrolyte bilayers for solar-cell applications[J]. Journal of the American Chemical Society, 2007, 129(29): 8958-8959. (d) Corbitt T S, Sommer J R, Chemburu S, et al. Conjugated polyelectrolyte capsules: light-activated antimicrobial micro "Roach Motels"[J]. ACS Applied Materials & Interfaces, 2009, 1(1): 48-52.

[21] Lu L D, Rininsland F H, Wittenburg S K, et al. Biocidal activity of a light-absorbing fluorescent conjugated polyelectrolyte[J]. Langmuir, 2005, 21(22): 10154-10159.

[22] Chemburu S, Corbitt T S, Ista L K, et al. Light-induced biocidal action of conjugated polyelectrolytes supported on colloids[J]. Langmuir, 2008, 24(19): 11053-11062.

[23] Corbitt T S, Ding L, Ji E, et al. Light and dark biocidal activity of cationic poly(arylene ethynylene) conjugated polyelectrolytes[J]. Photochemical & Photobiological Sciences, 2009, 8(7): 998-1005.

[24] (a) Zhu C L, Yang Q, Liu L B, et al. Visual optical discrimination and detection of microbial pathogens based on diverse interactions of conjugated polyelectrolytes with cells[J]. Journal of Materials Chemistry, 2011, 21(22): 7905-7912. (b) Zhu C L, Yang Q, Liu L B, et al. A potent fluorescent probe for the detection of cell apoptosis[J]. Chemical Communications, 2011, 47(19): 5524-5526.

[25] Ding L P, Chi E Y, Schanze K S, et al. Insight into the mechanism of antimicrobial conjugated polyelectrolytes: lipid headgroup charge and membrane fluidity effects[J]. Langmuir, 2010, 26(8): 5544-5550.

[26] Zhu C, Yang Q, Liu L, et al. Multifunctional cationic poly(p-phenylene vinylene) polyelectrolytes for selective recognition, imaging, and killing of bacteria over mammalian cells[J]. Advanced Materials, 2011, 23(41): 4805-4810.

[27] Gianferrara T, Bratsos I, Alessio E. A categorization of metal anticancer compounds based on their mode of action[J]. Dalton Transactions, 2009, (37): 7588-7598.

[28] (a) Zhou Q X, Lei W H, Chen J R, et al. A new heteroleptic ruthenium(II) polypyridyl complex with long-wavelength absorption and high singlet-oxygen quantum yield[J]. Chemistry-A European Journal, 2010, 16(10): 3157-3165. (b) Zhou Q X, Lei W H, Sun Y, et al. [Ru(bpy)_3-n(dpb)_n²⁺: unusual photophysical property and efficient DNA photocleavage activity[J]. Inorganic Chemistry, 2010, 49(11): 4729-4731.

[29] Lei W, Zhou Q, Jiang G, et al. Photodynamic inactivation of Escherichia coli by Ru(II) complexes[J]. Photochemical & Photobiological Sciences, 2011, 10(6): 887-890.

[30] Shao Q, Xing B. Enzyme responsive luminescent ruthenium(II) cephalosporin probe for intracellular imaging and photoinactivation of antibiotics resistant bacteria[J]. Chemical Communications, 2012, 48(12): 1739-1741.