Yarmush M L, Thorpe W P, Strong L, Rakestraw S L, Toner M, Tompkins R G
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08855-0909.
Crit Rev Ther Drug Carrier Syst. 1993;10(3):197-252.
The technique of Antibody Targeted Photolysis (ATPL) is reviewed from an historical perspective with a summary of the literature since the first experiments were performed in 1983. Attention is given to both the biological and photophysical properties of the various immunoconjugates that have been developed. References to critical discoveries and competing technologies in the photodynamic literature are given. Topics include: synthesis of immunoconjugates, in vitro vs. in vivo toxicity, in vivo biodistribution, immunoconjugate delivery, photosensitizer selection based on photophysical properties, light delivery for specific applications, oxygen requirements, and other physicochemical phenomena. A mathematical model of the dynamics for cell killing based upon the transport of phototoxins to the cell surface is developed. A generalized set of coupled differential equations is given, which conveniently summarizes the manifold requirements stressed earlier for successful cell killing. Solutions are then presented for an idealized set of conditions appropriate for an isolated tumor cell. Suggestions for further improvements and follow-up experiments are made that could help in the evolution of ATPL into a useful clinical therapy and/or probe for cell biological studies.
从历史角度回顾了抗体靶向光解技术(ATPL),总结了自1983年首次进行实验以来的文献。文中关注了已开发的各种免疫缀合物的生物学和光物理性质。还给出了光动力文献中关键发现和竞争技术的参考文献。主题包括:免疫缀合物的合成、体外与体内毒性、体内生物分布、免疫缀合物递送、基于光物理性质的光敏剂选择、特定应用的光递送、氧气需求以及其他物理化学现象。建立了基于光毒素向细胞表面转运的细胞杀伤动力学数学模型。给出了一组广义的耦合微分方程,方便地总结了前文强调的成功细胞杀伤的多种要求。然后针对适合分离肿瘤细胞的一组理想化条件给出了解决方案。提出了进一步改进和后续实验的建议,这有助于将ATPL发展成为一种有用的临床治疗方法和/或细胞生物学研究探针。