Zeng Yi-Ping, Luo Sheng-Lin, Yang Zhang-You, Huang Jia-Wei, Li Hong, Liu Cong, Wang Wei-Dong, Li Rong
State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 40038, China.
J Mater Chem B. 2016 Mar 28;4(12):2190-2198. doi: 10.1039/c6tb00108d. Epub 2016 Mar 8.
Targeted cancer therapies are currently a strong focus in biomedical research. Our recent studies have demonstrated that polyethylenimine-modified PEGylated nanographene loaded chlorin e6 (PPG-Ce6) shows excellent photodynamic efficacy because of the significantly enhanced intracellular targeted delivery of Ce6 to lysosomes. Based on our previous research, in this work, a novel nanographene-based tumor targeting delivery system was developed to selectively transport the photosensitizer into the tumor cells. In brief, we describe that the folic acid (FA) conjugated polyethylenimine-modified PEGylated nanographene system (PPG-FA) delivered in a targeted manner chlorin e6 (Ce6) to the tumor to simultaneously achieve targeted photodynamic therapy and biological imaging. The cellular internalization and the cellular uptake of PPG-FA-Ce6 were assessed, which indicated that the intracellular uptake of PPG-FA-Ce6 was target-specific. In vitro and in vivo photodynamic therapy results showed that PPG-FA-Ce6 exhibits excellent targeted delivery of Ce6, leading to simultaneous significant targeted photodynamic therapy and imaging. More importantly, the toxicity studies showed that PPG-FA-Ce6 had low toxicity as evidenced by blood biochemistry, hematological analysis, and histological examination. Our present work demonstrates that PPG-FA-Ce6 has high photodynamic therapy efficacy with no obvious toxicity because of its good tumor targeting property which can be potentially utilized in the biomedicine field.
靶向癌症治疗目前是生物医学研究的一个重点领域。我们最近的研究表明，聚乙烯亚胺修饰的聚乙二醇化纳米石墨烯负载的二氢卟吩e6（PPG-Ce6）由于二氢卟吩e6向溶酶体的细胞内靶向递送显著增强，显示出优异的光动力疗效。基于我们之前的研究，在这项工作中，开发了一种新型的基于纳米石墨烯的肿瘤靶向递送系统，以选择性地将光敏剂转运到肿瘤细胞中。简而言之，我们描述了叶酸（FA）共轭的聚乙烯亚胺修饰的聚乙二醇化纳米石墨烯系统（PPG-FA）以靶向方式将二氢卟吩e6（Ce6）递送至肿瘤，以同时实现靶向光动力治疗和生物成像。评估了PPG-FA-Ce6的细胞内化和细胞摄取，结果表明PPG-FA-Ce6的细胞摄取具有靶向特异性。体外和体内光动力治疗结果表明，PPG-FA-Ce6对二氢卟吩e6具有优异的靶向递送能力，从而导致同时进行显著的靶向光动力治疗和成像。更重要的是，毒性研究表明，血液生化、血液学分析和组织学检查证明PPG-FA-Ce6具有低毒性。我们目前的工作表明，PPG-FA-Ce6具有高光动力治疗疗效且无明显毒性，因为其良好的肿瘤靶向特性，可潜在地应用于生物医学领域。
