College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China.
ACS Appl Mater Interfaces. 2015 May 6;7(17):9287-96. doi: 10.1021/acsami.5b02297. Epub 2015 Apr 23.
Photodynamic therapy (PDT) has been recognized as a valuable treatment option for localized cancers. Herein, we demonstrate a cellular and subcellular targeted strategy to facilitate PDT efficacy. The PDT system was fabricated by incorporating a cationic porphyrin derivative (MitoTPP) onto the polyethylene glycol (PEG)-functionalized and folic acid-modified nanographene oxide (NGO). For this PDT system, NGO serves as the carrier for MitoTPP as well as the quencher for MitoTPP's fluorescence and singlet oxygen ((1)O2) generation. Attaching a hydrophobic cation to the photosensitizer ensures its release from NGO at lower pH values as well as its mitochondria-targeting capability. Laser confocal microscope experiments demonstrate that this dual-targeted nanosystem could preferably enter the cancer cells overexpressed with folate receptor, and release its cargo MitoTPP, which subsequently accumulates in mitochondria. Upon light irradiation, the released MitoTPP molecules generate singlet oxygen and cause oxidant damage to the mitochondria. Cell viability assays suggest that the dual-targeted nanohybrids exhibit much higher cytotoxicity toward the FR-positive cells.
光动力疗法（PDT）已被公认为治疗局限性癌症的一种有价值的治疗选择。在此，我们展示了一种细胞和亚细胞靶向策略，以提高 PDT 的疗效。PDT 系统是通过将阳离子卟啉衍生物（MitoTPP）结合到聚乙二醇（PEG）功能化和叶酸修饰的纳米氧化石墨烯（NGO）上而制成的。对于这个 PDT 系统，NGO 既是 MitoTPP 的载体，也是 MitoTPP 的荧光和单线态氧（(1)O2）产生的猝灭剂。将疏水分子附着在光敏剂上，可确保其在较低 pH 值下从 NGO 中释放出来，并具有靶向线粒体的能力。激光共聚焦显微镜实验表明，这种双重靶向纳米系统可以优先进入过表达叶酸受体的癌细胞，并释放其货物 MitoTPP，随后 MitoTPP 积聚在线粒体中。在光照射下，释放的 MitoTPP 分子产生单线态氧，并对线粒体造成氧化损伤。细胞活力测定表明，这种双重靶向纳米杂化物对 FR 阳性细胞表现出更高的细胞毒性。
