Enhanced in vivo antitumor efficacy of poorly soluble PDT agent, meso-tetraphenylporphine, in PEG-PE-based tumor-targeted immunomicelles
Enhanced in vivo antitumor efficacy of poorly soluble PDT agent, meso-tetraphenylporphine, in PEG-PE-based tumor-targeted immunomicelles
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DOI：
10.4161/cbt.6.7.4345
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Torchilin, Vladimir P.
中科院分区：
文献类型：
--
作者：
Roby, Aruna;Erdogan, Stma;Torchilin, Vladimir P.
用聚乙二醇-磷脂酰乙醇胺偶联物（PEG-PE）制备的聚合物胶束增溶难溶性光敏剂meso-四苯基卟啉（TPP）。用肿瘤特异性单克隆抗体2C5（mAb 2C5）对载TPP的PEG-PE胶束进行了修饰，这导致在PDT条件下对小鼠刘易斯肺癌（LLC）的抗癌作用显著提高。在肿瘤接种后14天，对具有直径大于2mm的肿瘤的小鼠静脉内注射lmg/kg的游离TPP或加载到对照PEG-PE胶束或mAb 2C5-PEG-PE肿瘤靶向免疫胶束中的TPP。给药后24小时，将动物麻醉，用光（630 nm）照射肿瘤部位12 min。在光照射后24小时，对部分小鼠进行肿瘤反应的显微镜评价，并在其余动物中跟踪肿瘤大小35天。mAb 2C5与负载TPP的免疫胶束的连接提供了最大水平的肿瘤生长抑制。通过γ成像研究证实了负载TPP的mAb 2C5-PEG-PE-免疫胶束的增强的肿瘤蓄积。用肿瘤特异性抗体修饰载TPP的聚合物胶束可作为增强PDT疗效的一般方法。
Poorly soluble photosensitizer, meso-tetraphenylporphine (TPP), was solubilized using the polymeric micelles prepared from polyethylene glycol-phosphatidyl ethanolamine conjugate (PEG-PE). TPP-loaded PEG-PE micelles have been additionally modified with tumor-specific monoclonal 2C5 antibody (mAb 2C5), which resulted in significantly improved anticancer effect of the drug under the PDT conditions against murine Lewis lung carcinoma (LLC) In vivo in female C57BL/6 mice. Fourteen days after tumor inoculation, the mice with more than 2 mm diameter tumors were given an intravenous injection of 1 mg/kg of free TPP or TPP loaded into control PEG-PE micelles or into mAb 2C5-PEG-PE tumor-targeted immunomicelles. Twenty-four hours after the administration, the animals were anesthetized, and tumor sites were illuminated with light (630 nm) for 12 min. Microscopic evaluation of tumor response was conducted in some mice 24 h after light irradiation, and tumor size was followed in the remaining animals for another 35 days. The attachment of mAb 2C5 to TPP-loaded immunomicelles provided the maximum level of tumor growth inhibition. Enhanced tumor accumulation of TPP-loaded mAb 2C5-PEG-PE-immunomicelles was confirmed by gamma-imaging studies. The modification of the TPP-loaded polymeric micelles with tumor-specific antibodies could be used as a general approach to enhance the efficacy of PDT.