Targeted Iron-Oxide Nanoparticle for Photodynamic Therapy and Imaging of Head and Neck Cancer

• Type of Material: Article
• Authors: Dongsheng Wang, Emory University; Baowei Fei, Emory University; Luma V. Halig, Emory University; Xulei Qin, Emory University; Zhongliang Hu, Emory University; Hong Xu, Ocean NanoTech LLC; Yongqiang Andrew Wang, Ocean NanoTech LLC; Zhengjia Chen, Emory University; Sungjin Kim, Emory University; Dong Shin, Emory University; Georgia Chen, Emory University
• Language: English
• Date: 2014-07-01
• Publisher: American Chemical Society
• Publication Version: Final Published Version
• Copyright Statement: © 2014 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
• Final Published Version (URL): http://dx.doi.org/10.1021/nn501652j
• Title of Journal or Parent Work: ACS Nano
• ISSN: 1936-0851
• Volume: 8
• Issue: 7
• Start Page: 6620
• End Page: 6632
• Grant/Funding Information: National Institutes of Health, United States; This research was supported in part by NIH grants R01CA156775 (PI: Fei) and R21CA176684 (PI: Fei), Georgia Cancer Coalition Distinguished Clinicians and Scientists Awards (PIs: Fei and Chen), and Emory Molecular and Translational Imaging Center (NIH P50CA128301).
• Keywords: Physical Sciences; Chemistry, Multidisciplinary; DRUG-DELIVERY; integrin beta 1; Chemistry, Physical; magnetic resonance Imaging; TUMOR; Nanoscience & Nanotechnology; NANOSCIENCE & NANOTECHNOLOGY; HUMAN SERUM-ALBUMIN; Science & Technology; Chemistry; MAGNETIC NANOPARTICLES; GROWTH-FACTOR; photodynamic therapy; CHEMISTRY, PHYSICAL; head and neck cancer; LYMPH-NODE METASTASES; Fmp-IO-Pc 4; PROSTATE-CANCER; FIBRONECTIN-MIMETIC PEPTIDE; Science & Technology - Other Topics; iron-oxide nanoparticle; IN-VITRO; CHEMISTRY, MULTIDISCIPLINARY; SQUAMOUS-CELL CARCINOMA; Technology; Materials Science, Multidisciplinary; Materials Science; MATERIALS SCIENCE, MULTIDISCIPLINARY
• Research Categories: Biology, Bioinformatics; Biology, Biostatistics; Health Sciences, Oncology

Abstract

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.