Department of Biotechnology, Center for Photomedicine, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi do 420-743, Korea.
Macromol Biosci. 2015 Aug;15(8):1081-90. doi: 10.1002/mabi.201500060. Epub 2015 Mar 31.
The accurate diagnosis and proper therapy for cancer are essential to improve the success rate of cancer treatment. Here, we demonstrated that the vitamin Bc -bearing hydrophilic photosensitizer conjugate folic acid-polyethylene glycol-pheophorbideA (FA-PEG-PheoA) has been synthesized for the intracellular diagnosis and photodynamic therapy of a tumor. The synthesized vitamin Bc -bearing hydrophilic photosensitizer conjugate has been characterized for the folic acid receptor expressing the ability to target tumor cells, which is facilitated by the chemical conjugation with folic acid. The vitamin Bc -bearing hydrophilic photosensitizer conjugate internalization mechanism was identified through a competitive inhibition test with free folic acid. We optimized the laser-sensitive, cytotoxicity changeable, vitamin Bc -bearing hydrophilic photosensitizer conjugate concentration, which is non-cytotoxic under normal conditions and specifically cytotoxic toward cancer cells (maximum 69.15%) under laser irradiation conditions used for theranostic agents. The cancer therapeutic and diagnosis effects of synthesized conjugate were confirmed in MDA-MB-231 cells and MDA-MB-231-bearing mice. As a result, the vitamin Bc -bearing hydrophilic photosensitizer conjugate exhibited a highly photodynamic therapeutic effect, which enabled the selective detection of a folic acid receptor expressing cancer using optical imaging.
准确的癌症诊断和适当的治疗对于提高癌症治疗的成功率至关重要。在这里，我们展示了一种含有维生素 Bc 的亲水性光敏剂缀合物叶酸-聚乙二醇-脱镁叶绿酸 A（FA-PEG-PheoA）的合成，用于肿瘤的细胞内诊断和光动力治疗。合成的含有维生素 Bc 的亲水性光敏剂缀合物具有叶酸受体表达能力，能够靶向肿瘤细胞，这得益于与叶酸的化学缀合。通过与游离叶酸的竞争抑制试验，确定了含有维生素 Bc 的亲水性光敏剂缀合物的内化机制。我们优化了激光敏感、细胞毒性变化、含有维生素 Bc 的亲水性光敏剂缀合物浓度，在正常条件下无毒，在激光照射条件下对癌细胞具有特异性细胞毒性（最高 69.15%），用于治疗诊断试剂。在 MDA-MB-231 细胞和 MDA-MB-231 荷瘤小鼠中证实了合成缀合物的癌症治疗和诊断效果。结果表明，含有维生素 Bc 的亲水性光敏剂缀合物表现出高度的光动力治疗效果，能够利用光学成像选择性地检测表达叶酸受体的癌症。
