Ferritin Nanocages To Encapsulate and Deliver Photosensitizers for Efficient Photodynamic Therapy against Cancer

• Published in: ACS nano Vol. 7; no. 8; pp. 6988 - 6996
• Main Authors: Zhen, Zipeng, Tang, Wei, Guo, Cunlan, Chen, Hongmin, Lin, Xin, Liu, Gang, Fei, Baowei, Chen, Xiaoyuan, Xu, Binqian, Xie, Jin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.08.2013
• Subjects: Animals; Cancer; Cell Line, Tumor; DNA - chemistry; Drug Carriers; Drug Screening Assays, Antitumor; Encapsulation; Ferritin; Ferritins - chemistry; Humans; Mice; Mice, Nude; Microscopy, Fluorescence; Nanomedicine - methods; Nanoparticles - chemistry; Nanostructure; Neoplasm Transplantation; Neoplasms - drug therapy; Oxygen - chemistry; Particle Size; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - pharmacology; Surface Properties; Time Factors; Tissue Distribution; Tumors; Vehicles; Zinc; Zinc - chemistry; targeted delivery; nanoparticle; ferritin; photodynamic therapy; photosensitizer
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/nn402199g

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.