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首页> 外文会议>Optical methods for tumor treatment and detection: mechanisms and techniques in photodynamic therapy XX >MS2 bacteriophage as a delivery vessel of porphyrins for photodynamic therapy
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MS2 bacteriophage as a delivery vessel of porphyrins for photodynamic therapy

机译：MS2噬菌体作为卟啉的传递容器，用于光动力治疗

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Challenges associated with photodynamic therapy (PDT) include the packaging and site-specific delivery of therapeutic agents to the tissue of interest. Nanoscale encapsulation of PDT agents inside targeted virus capsids is a novel concept for packaging and site-specific targeting. The icosahedral MS2 bacteriophage is one potential candidate for such a packaging-system. MS2 has a porous capsid with an exterior diameter of ~28 nm where the pores allow small molecules access to the capsid interior. Furthermore, MS2 presents suitable residues on the exterior capsid for conjugation of targeting ligands. Initial work by the present investigators has successfully demonstrated RNA-based self-packaging of a heterocyclic PDT agent (meso-tetrakis(para-N-trimethylanilinium)porphine, TMAP) into the MS2 capsid. Packaging photoactive compounds in confined spaces could result in energy transfer between the molecules upon photoactivation, which could in turn reduce the production of radical oxygen species (ROS). ROS are key components in photodynamic therapy, and a reduced production could negatively impact the efficacy of PDT treatment. Here, findings are presented from an investigation of ROS generation of TMAP encapsulated within the MS2 capsid compared to free TMAP in solution. Monitoring of ROS production upon photoactivation via a specific singlet oxygen assay revealed the impact on ROS generation between packaged porphyrins as compared to free porphyrin in an aqueous solution. Follow on work will study the ability of MS2-packaged porphyrins to generate ROS in vitro and subsequent cytotoxic effects on cells in culture.
机译：与光动力疗法（PDT）相关的挑战包括治疗药物向目标组织的包装和部位特异性递送。 PDT剂在靶向病毒衣壳内的纳米级封装是用于包装和针对特定位点靶向的新概念。二十面体MS2噬菌体是这种包装系统的一种潜在候选物。 MS2具有一个外径约为28 nm的多孔衣壳，其中的孔允许小分子进入衣壳内部。此外，MS2在外衣壳上具有合适的残基，可与靶向配体结合。本研究人员的初步工作已成功地证明了基于杂环的PDT试剂（间-四（对-N-三甲基苯胺基）卟啉，TMAP）基于RNA的自包装进入MS2衣壳。将光敏化合物包装在狭窄的空间中可能会导致光活化后分子之间的能量转移，进而降低自由基氧（ROS）的产生。 ROS是光动力疗法的关键组成部分，产量降低可能会对PDT治疗的功效产生负面影响。在这里，与溶液中的游离TMAP相比，通过封装在MS2衣壳中的TMAP的ROS生成的研究提出了发现。通过特定的单线态氧测定法对光活化后产生的ROS进行监测，发现与水溶液中的游离卟啉相比，对包装的卟啉之间的ROS产生有影响。后续工作将研究MS2包装的卟啉在体外产生ROS的能力以及随后对培养细胞的细胞毒性作用。

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