Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer.
Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer.
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DOI：
10.1021/nn402199g
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发表时间：
2013-08-27
期刊：
影响因子：
17.1
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Zhen Z;Tang W;Guo C;Chen H;Lin X;Liu G;Fei B;Chen X;Xu B;Xie J
光动力疗法是一种新兴的治疗方法，目前正在对包括癌症在内的多种疾病进行深入的临床前和临床研究。尽管前景看好，但目前还缺乏一种可靠的药物输送载体，可以将光敏剂(PSS)以特定部位的方式运送到肿瘤。以前的研究主要集中在聚合物或脂质体为基础的纳米载体上，这通常与PS负载率和大颗粒尺寸有关。我们在这里报道了RGD4C修饰的铁蛋白(RFRT)，一种基于蛋白质的纳米颗粒，可以作为一种安全和高效的PS载体。十六氟邻苯二甲酸锌(ZnF16Pc)是一种高效的PS，具有较高的氧量子产率，但水溶性较差，其负载率高达~60wt%(即1 mg RFRT可负载1.5 mg的ZnF16Pc)，远远超过以往的文献报道。尽管负载量很高，但负载的锌氟碳纳米载体(P-RFRT)的总粒径为18.6±2.6 nm，明显小于其他PS-纳米载体结合物。在U87 MG皮下肿瘤模型上实验表明，P-RFRT具有较高的肿瘤聚集率(24小时肿瘤与正常组织之比为26.82±4.07)，良好的肿瘤抑制率(第12天为83.64%)，且对皮肤和其他主要器官的毒性最小。这项技术可以扩展到提供其他含有金属的PSS，并具有巨大的临床翻译潜力。
Photodynamic therapy is an emerging treatment modality that is under intensive preclinical and clinical investigations for many types of disease including cancer. Despite the promise, there is a lack of a reliable drug delivery vehicle that can transport photosensitizers (PSs) to tumors in a site-specific manner. Previous efforts have been focused on polymer- or liposome-based nanocarriers, which are usually associated with a suboptimal PS loading rate and a large particle size. We report herein that a RGD4C-modified ferritin (RFRT), a protein-based nanoparticle, can serve as a safe and efficient PS vehicle. Zinc hexadecafluorophthalocyanine (ZnF16Pc), a potent PS with a high 1O2 quantum yield but poor water solubility, can be encapsulated into RFRTs with a loading rate as high as ~60 wt % (i.e., 1.5 mg of ZnF16Pc can be loaded on 1 mg of RFRTs), which far exceeds those reported previously. Despite the high loading, the ZnF16Pc-loaded RFRTs (P-RFRTs) show an overall particle size of 18.6 ± 2.6 nm, which is significantly smaller than other PS–nanocarrier conjugates. When tested on U87MG subcutaneous tumor models, P-RFRTs showed a high tumor accumulation rate (tumor-to-normal tissue ratio of 26.82 ±4.07 at 24 h), a good tumor inhibition rate (83.64% on day 12), as well as minimal toxicity to the skin and other major organs. This technology can be extended to deliver other metal-containing PSs and holds great clinical translation potential.