Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013 Hunan Province, P. R. China.
Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 Hunan Province, P. R. China.
Mol Pharm. 2020 Aug 3;17(8):2882-2890. doi: 10.1021/acs.molpharmaceut.0c00335. Epub 2020 Jul 9.
Pyropheophorbide a (Pyro) is a widely used photosensitizer for photodynamic therapy (PDT). However, poor water solubility, aggregation-induced fluorescence quenching, and lack of selectivity to targeted cells seriously limit its application. In this work, we prepared aptamer-Pyro conjugates (APCs) by linking Pyro to hydrophilic nucleic acid aptamer to enhance its water solubility and endow it with protein tyrosine kinase 7 (PTK7) overexpressed tumor spheroid specific targeting and penetration abilities for photodynamic therapy. The molecular conjugate was successfully synthesized and dissolved well in an aqueous solution. The APCs showed strong near-infrared fluorescence in the aqueous solution and produced singlet oxygen both in the solution and cells under laser irradiation, indicating its generation of singlet oxygen during PDT was guaranteed. Owing to the cancer cell targeting ability of the aptamer, the APCs specifically bound with PTK7 overexpressed cancerous cells and showed fluorescence signal for tumor cell imaging and diagnosis. The APCs exhibited favorable enhanced phototoxicity to target tumor cells compared with control cells. More importantly, due to the small size of the molecular conjugate, the APCs efficiently penetrated into the interior of multicellular tumor spheroids (MCTS) and caused cell damage. All these results indicated that the robust aptamer-Pyro conjugate is a promising selective tumor-targeting and penetrable molecule for cancer photodynamic therapy.
苝酰亚胺（Pyro）是一种广泛应用于光动力疗法（PDT）的光敏剂。然而，较差的水溶性、聚集诱导荧光猝灭以及缺乏对靶细胞的选择性严重限制了其应用。在本工作中，我们通过将 Pyro 与亲水性核酸适体连接，制备了适体-Pyro 缀合物（APCs），以提高其水溶性，并赋予其蛋白酪氨酸激酶 7（PTK7）过表达肿瘤球体的特异性靶向和穿透能力，用于光动力治疗。该分子缀合物成功合成并很好地溶解在水溶液中。APCs 在水溶液中显示出强近红外荧光，并在激光照射下在溶液中和细胞中产生单线态氧，表明其在 PDT 期间产生单线态氧得到保证。由于适体的癌细胞靶向能力，APCs 特异性地与过表达 PTK7 的癌细胞结合，并显示出荧光信号，用于肿瘤细胞的成像和诊断。与对照细胞相比，APCs 对靶肿瘤细胞表现出良好的增强光毒性。更重要的是，由于分子缀合物的尺寸较小，APCs 能够有效地穿透到多细胞肿瘤球体（MCTS）的内部并引起细胞损伤。所有这些结果表明，强大的适体-Pyro 缀合物是一种有前途的用于癌症光动力治疗的选择性肿瘤靶向和可穿透分子。
