Despite the high in vitro efficacy of photodynamic therapeutics, lack of tumor targeting significantly reduces their in vivo efficacy and thus limits their clinical use. Photoimmunotherapy (PIT) is a new synthetic strategy to target and treat cancer by photodynamic therapy (PDT). In this study, we describe design and synthesis of a third-generation photosensitizer comprising a PEGylated-phthalocyanine star-polymer photosensitizer that covalently bound to a myeloma tumor-selective antibody (MAb) via the carbodiimide chemistry. The free photosensitizer demonstrated a minimum dark toxicity when tested in mammalian myeloma cell line (SP2/OR); and a moderate phototoxicity after irradiation with non thermal laser red light as a result of light-induced production of cytotoxic singlet oxygen species. Covalent attachment of the photosensitizer (Pc) to the MAb resulted in a significantly enhanced phototoxicity. This is mainly ascribed to the fact that internalization enhances phototoxicity of Pc-MAb bioconjugates. The radioactivated photoimmuno-conjugates 131I(PcMAb) demonstrated the highest phototoxicity to myeloma cells. The suggested bioconjugates are promising candidates as multiple therapeutic models for in vivo treatment of myeloma.

中文翻译：

---

基于光敏剂-抗体偶联物的靶向光免疫疗法用于多发性骨髓瘤的治疗。

尽管光动力疗法具有很高的体外疗效，但缺乏肿瘤靶向性显着降低了其体内疗效，因此限制了其临床应用。光免疫疗法（PIT）是一种通过光动力疗法（PDT）靶向和治疗癌症的新型合成策略。在这项研究中，我们描述了第三代光敏剂的设计和合成，该第三代光敏剂包含通过碳二亚胺化学共价结合到骨髓瘤肿瘤选择性抗体（MAb）的PEG化酞菁星型聚合物光敏剂。当在哺乳动物骨髓瘤细胞系（SP2 / OR）中进行测试时，这种游离的光敏剂显示出最小的暗毒性。在非热激光红光照射后，由于光诱导的细胞毒性单线态氧物种的产生，具有中等的光毒性。光敏剂（Pc）与MAb的共价结合导致光毒性显着增强。这主要归因于以下事实：内在化增强了Pc-MAb生物缀合物的光毒性。放射性光免疫偶联物131I（PcMAb）对骨髓瘤细胞表现出最高的光毒性。所提出的生物缀合物有望作为体内治疗骨髓瘤的多种治疗模型的候选物。