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

• Authors: Zipeng Zhen, University of Georgia; Wei Tang, University of Georgia; Cunlan Guo, University of Georgia; Hongmin Chen, University of Georgia; Xin Lin, National Institute of Biomedical Imaging and Bioengineering; Gang Liu, Xiamen University; Baowei Fei, Emory University; Xiaoyuan Chen, National Institute of Biomedical Imaging and Bioengineering; Binqian Xu, University of Georgia; Jin Xie, University of Georgia
• Journal Title: ACS Nano
• Volume: Volume 7, Number 8
• Publisher: American Chemical Society | 2013-08-01, Pages 6988-6996
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1021/nn402199g
• Subjects: Chemistry, Physical; Health Sciences, Oncology
• Keywords: Science & Technology; Physical Sciences; Technology; Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Chemistry; Science & Technology - Other Topics; Materials Science; photodynamic therapy; photosensitizer; targeted delivery; ferritin; nanoparticle; ZINC PHTHALOCYANINE; PROSTATE-CANCER; COMBINATION THERAPY; DRUG-DELIVERY; NANOPARTICLES; APOFERRITIN; TUMORS; GROWTH; MODEL

Abstract

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 (ZnF 16 Pc), a potent PS with a high 1 O 2 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 ZnF 16 Pc can be loaded on 1 mg of RFRTs), which far exceeds those reported previously. Despite the high loading, the ZnF 16 Pc-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.