title: Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer.
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 (ZnF16Pc), a potent PS with a high (1)O2 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.
authors.affiliation: Department of Chemistry, Bio-Imaging Research Center, University of Georgia, Athens, Georgia 30602, United States.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Zhen
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Cunlan
authors.initials: C
authors.lastname: Guo
authors.forename: Hongmin
authors.initials: H
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Baowei
authors.initials: B
authors.lastname: Fei
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Binqian
authors.initials: B
authors.lastname: Xu
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D005293:Ferritins / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D010100:Oxygen / Q000737:chemistry; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013499:Surface Properties; D013997:Time Factors; D014018:Tissue Distribution; D015032:Zinc / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D017319:Photosensitizing Agents; D004247:DNA; D005293:Ferritins; D015032:Zinc; D010100:Oxygen