New "light" for one-world approach toward safe and effective control of animal diseases and insect vectors from leishmaniac perspectives.
New "light" for one-world approach toward safe and effective control of animal diseases and insect vectors from leishmaniac perspectives.
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DOI：
10.1186/s13071-016-1674-3
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发表时间：
2016-07-13
影响因子：
3.2
通讯作者：
New Light Group
中科院分区：
文献类型：
--
作者：
Chang KP;Kolli BK;New Light Group
已知光在氧存在下激发光敏剂（PS）以产生细胞毒性活性氧物质（ROS）。这一模式对于制定防治动物疾病和害虫的措施很有吸引力。许多PS都有可靠的安全记录。此外，ROS细胞毒性不选择耐药突变体，不像其他药物和农药。光动力疗法（PDT）是指在医学和农业中使用PS作为光活化的杀肿瘤剂、杀微生物剂和杀虫剂。在这里，我们描述了“光动力疫苗接种”（PDV），使用PDT灭活的寄生虫，即利什曼原虫作为全细胞疫苗对利什曼病，并作为一个通用的载体，提供转基因附加疫苗对其他传染病和恶性疾病。利什曼原虫用于疫苗递送的功效利用它们的固有属性来寄生抗原（疫苗）呈递细胞。通过PDT灭活利什曼原虫为其使用提供了安全性。这是通过两种不同的方式实现的：（i）PS的化学工程以增强其摄取，例如Si-酞菁;和（ii）转基因方法以使利什曼原虫可诱导卟啉生成。三种不同的计划，利什曼病为基础的PDV图示描绘细胞事件导致细胞介导的免疫力，如实验所见，对利什曼病和利什曼病交付的抗原在体外和体内。PDT灭活利什曼原虫的安全性与有效性评价正在进行中，包括进一步处理以便于储存和运输的利什曼原虫。被转染以表达癌症的利什曼原虫和病毒疫苗候选物正在相应地准备用于实验性试验。我们已经开始研究PS介导的光动力杀虫剂（PDI）。苔藓细胞吸收虎红/氰核苷，使它们对光敏感，从而在体外进行崩解，从而为相同处理所观察到的杀幼虫活性提供细胞基础。酞菁和卟啉对PDI的无效性强调了其对不同PS的要求。昆虫与其他细胞对PS的差异吸收正在研究中，以解释这种差异。正在进行的工作是按照“一个世界”的办法进行的，争取药物化学、细胞/分子生物学、免疫学、寄生虫学、昆虫学、癌症研究、热带医学和兽医学方面的专家参加。多学科专业知识的可用性对于实施必要的研究以将项目推向产品开发是必不可少的。
Light is known to excite photosensitizers (PS) to produce cytotoxic reactive oxygen species (ROS) in the presence of oxygen. This modality is attractive for designing control measures against animal diseases and pests. Many PS have a proven safety record. Also, the ROS cytotoxicity selects no resistant mutants, unlike other drugs and pesticides. Photodynamic therapy (PDT) refers to the use of PS as light activable tumoricides, microbicides and pesticides in medicine and agriculture. Here we describe “photodynamic vaccination” (PDV) that uses PDT-inactivation of parasites, i.e. Leishmania as whole-cell vaccines against leishmaniasis, and as a universal carrier to deliver transgenic add-on vaccines against other infectious and malignant diseases. The efficacy of Leishmania for vaccine delivery makes use of their inherent attributes to parasitize antigen (vaccine)-presenting cells. Inactivation of Leishmania by PDT provides safety for their use. This is accomplished in two different ways: (i) chemical engineering of PS to enhance their uptake, e.g. Si-phthalocyanines; and (ii) transgenic approach to render Leishmania inducible for porphyrinogenesis. Three different schemes of Leishmania-based PDV are presented diagrammatically to depict the cellular events resulting in cell-mediated immunity, as seen experimentally against leishmaniasis and Leishmania-delivered antigen in vitro and in vivo. Safety versus efficacy evaluations are under way for PDT-inactivated Leishmania, including those further processed to facilitate their storage and transport. Leishmania transfected to express cancer and viral vaccine candidates are being prepared accordingly for experimental trials. We have begun to examine PS-mediated photodynamic insecticides (PDI). Mosquito cells take up rose bengal/cyanosine, rendering them light-sensitive to undergo disintegration in vitro, thereby providing a cellular basis for the larvicidal activity seen by the same treatments. Ineffectiveness of phthalocyanines and porphyrins for PDI underscores its requirement for different PS. Differential uptake of PS by insect versus other cells to account for this difference is under study. The ongoing work is patterned after the one-world approach by enlisting the participation of experts in medicinal chemistry, cell/molecular biology, immunology, parasitology, entomology, cancer research, tropical medicine and veterinary medicine. The availability of multidisciplinary expertise is indispensable for implementation of the necessary studies to move the project toward product development.