Sioud Mouldy, Juzenas Petras, Zhang Qindong, Kleinauskas Andrius, Peng Qian
Division of Cancer Medicine, Department of Cancer Immunology, Oslo University Hospital, University of Oslo, Ullernchausseen 70, 0379 Oslo, Norway.
Division of Laboratory Medicine, Department of Pathology, Oslo University Hospital-Radiumhospitalet, Ullernchausseen 70, 0379 Oslo, Norway.
Cancers (Basel). 2021 Jul 4;13(13):3356. doi: 10.3390/cancers13133356.
Photodynamic therapy (PDT) is a treatment strategy that utilizes photosensitizers (PSs) and light of a specific wavelength to kill cancer cells. However, limited tumor specificity is still a drawback for the clinical application of PDT. To increase the therapeutic efficacy and specificity of PDT, a novel human minibody (MS5) that recognizes a cell surface receptor expressed on various cancer cells was labeled with the hydrophilic phthalocyanine PS IR700 to generate an MS5-IR700 conjugate that is activated by near-infrared (NIR) light. The phototoxicity of the conjugate was mainly tested against the PC3 prostate cancer cell line. The MS5-IR700 conjugate killed PC3 cells after NIR light irradiation as compared to untreated cells or cells treated with IR700 alone. Time-course analysis of cell viability revealed a high percentage of cell death during the first hour in PC3 cells exposed to the MS5-IR700 conjugate and NIR light irradiation. After irradiation, the MS5-IR700 conjugate-treated PC3 cells displayed cellular swelling, round shape, and rupture of the cell and nuclear membranes. In a co-culture model, the MS5-IR700 conjugate killed MS5-positive Ramos lymphoma cells specifically, while leaving MS5-negative cells unaffected. In line with the data obtained with the monolayer cultures, the MS5-IR700 conjugate also killed PC3 cancer cell spheroids. The treatment induced relocation of heat shock protein 70 and calreticulin to the cell surface, implying the induction of immunogenic cell death. Overall, the data suggest that the developed MS5-IR700 conjugate is a promising therapeutic agent that warrants further preclinical studies.
光动力疗法（PDT）是一种利用光敏剂（PSs）和特定波长的光来杀死癌细胞的治疗策略。然而，肿瘤特异性有限仍是PDT临床应用的一个缺点。为了提高PDT的治疗效果和特异性，一种识别多种癌细胞表面表达的细胞表面受体的新型人微型抗体（MS5）用亲水性酞菁PS IR700进行标记，以生成由近红外（NIR）光激活的MS5-IR700偶联物。该偶联物的光毒性主要针对PC3前列腺癌细胞系进行测试。与未处理的细胞或仅用IR700处理的细胞相比，MS5-IR700偶联物在近红外光照射后杀死了PC3细胞。细胞活力的时间进程分析显示，在暴露于MS5-IR700偶联物和近红外光照射的PC3细胞中，在第一个小时内细胞死亡的比例很高。照射后，经MS5-IR700偶联物处理的PC3细胞出现细胞肿胀、圆形以及细胞膜和核膜破裂。在共培养模型中，MS5-IR700偶联物特异性地杀死了MS5阳性的拉莫斯淋巴瘤细胞，而使MS5阴性细胞不受影响。与单层培养获得的数据一致，MS5-IR700偶联物也杀死了PC3癌细胞球体。该处理诱导热休克蛋白70和钙网蛋白重新定位到细胞表面，这意味着诱导了免疫原性细胞死亡。总体而言，数据表明所开发的MS5-IR700偶联物是一种有前景的治疗剂，值得进一步进行临床前研究。
