Wang Dongsheng, Fei Baowei, Halig Luma V, Qin Xulei, Hu Zhongliang, Xu Hong, Wang Yongqiang Andrew, Chen Zhengjia, Kim Sungjin, Shin Dong M, Chen Zhuo Georgia
ACS Nano. 2014 Jul 22;8(7):6620-32. doi: 10.1021/nn501652j.
Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic.
光动力疗法（PDT）是一种针对多种癌症的高度特异性抗癌治疗方式，尤其适用于对传统抗癌疗法不再有反应的复发性癌症。光动力疗法已经研发了数十年，但与光相关的毒性限制了其临床应用。为降低光动力疗法的毒性，我们最近开发了一种靶向纳米颗粒（NP）平台，该平台将第二代光动力疗法药物Pc 4与癌症靶向配体以及氧化铁（IO）纳米颗粒相结合。首先将羧基功能化的IO纳米颗粒与结合整合素β1的纤连蛋白模拟肽（Fmp）偶联。然后将光动力疗法药物Pc 4成功封装到配体偶联的IO纳米颗粒中，生成Fmp-IO-Pc 4。我们的研究表明，非靶向的IO-Pc 4和靶向的Fmp-IO-Pc 4纳米颗粒在异种移植肿瘤中的蓄积浓度均高于未配制的Pc 4。正如预期的那样，IO-Pc 4和Fmp-IO-Pc 4对头颈部鳞状细胞癌异种移植肿瘤大小的缩小作用均比游离的Pc 4更有效。与文献报道的剂量相比，靶向的Fmp-IO-Pc 4纳米颗粒使用的Pc 4剂量低10倍，但其对肿瘤生长的抑制作用明显大于非靶向的IO-Pc 4纳米颗粒。这些结果表明，通过IO纳米颗粒递送光动力疗法药物Pc 4可以提高治疗效果并降低光动力疗法药物的剂量。靶向的IO-Pc 4纳米颗粒在临床上有很大潜力同时作为磁共振成像（MRI）剂和光动力疗法药物。
