Photodynamic Blood Product Decontamination

光动力血液制品净化

• 批准号: 6739457
• 负责人: J TIM WHARTON
• 金额: $ 19.88万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739457
• 关键词: bioengineering /biomedical engineering; biomedical equipment development; blood bank /supply contamination; clinical research; free radical oxygen; hydropathy; nonvisual photosensitivity; plasma; platelets; polymers; portable biomedical equipment

DESCRIPTION (provided by applicant): The objective of this proposal is to covalently immobilize an all-carbon nanoparticle that is an excellent photosensitizer (PS) onto biologically inert polymeric backbones for the photodynamic inactivation of pathogens in blood products. The polymers will then be placed in a permeable cartridge and fixed into a flow-through reactor. After filling the reactor with the blood product, the fluid will be circulated and the photocatalyst illuminated with laser light. The illuminated PS catalyzes the formation of singlet oxygen, 1O2*, a reactive species of oxygen that will inactivate pathogens in the blood product. The decontaminated blood product is then simply removed from the reactor, leaving the C60-modified polymer behind. Three types of polymeric backbones will be investigated: 1) hydrophobic polymer, 2) polycationic polymer, 3) non-ionic hydrophilic polymer. The synthetic steps to modify the polymers with C60 start from commercially available polymers and are simple literature procedures. After photocatalyst synthesis and construction of the reactor, the pathogen inactivation system will be evaluated in a series of in vitro experiments to determine the optimal blood product decontamination applications of the new system. Several advantages are expected over conventional homogeneous PS such as methylene blue: 1) there is no post-treatment toxicity because the photocatalyst is heterogeneous and integrated into the reactor structure and upon completion of treatment, the blood product is simply removed from the reactor leaving the catalyst behind, 2) enhanced selectivity of pathogen inactivation is expected due to the polymeric backbone's tunable affinity relative to damage to blood components 3) the nanoparticle PS that will be used has a very high singlet oxygen quantum yield, higher than conventional PS The vision of this project is to introduce a novel, economical system to the blood product market for the inactivation of pathogens in blood products.

描述（由申请人提供）：本提案的目的是将一种优异的光敏剂（PS）全碳纳米颗粒共价包埋到生物惰性聚合物主链上，用于血液制品中病原体的光动力灭活。然后将聚合物放置在可渗透的筒中并固定到流通式反应器中。在用血液制品填充反应器之后，流体将被循环，并且光催化剂用激光照射。被照射的PS催化单线态氧1O2* 的形成，1O2* 是一种活性氧物质，将抑制血液制品中的病原体。然后将净化的血液产品简单地从反应器中取出，留下C60改性的聚合物。 将研究三种类型的聚合物主链：1）疏水聚合物，2）聚阳离子聚合物，3）非离子亲水聚合物。用C60改性聚合物的合成步骤从市售聚合物开始，并且是简单的文献程序。在光催化剂合成和反应器的构建之后，将在一系列体外实验中评估病原体灭活系统，以确定新系统的最佳血液制品去污应用。 与传统的均匀PS（如亚甲蓝）相比，预期有几个优点：1）没有后处理毒性，因为光催化剂是多相的并且整合到反应器结构中，并且在处理完成时，血液制品简单地从反应器中除去，留下催化剂，2）由于聚合物主链相对于对血液组分的损伤的可调亲和力，预期病原体灭活的选择性增强将使用的纳米颗粒PS具有非常高的单线态氧量子产率，高于常规PS 该项目的愿景是为血液制品市场引入一种新型、经济的系统，用于灭活血液制品中的病原体。