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

• Published in: ACS nano Vol. 8; no. 7; pp. 6620 - 6632
• Main Authors: Wang, Dongsheng, Fei, Baowei, Halig, Luma V, Qin, Xulei, Hu, Zhongliang, Xu, Hong, Wang, Yongqiang Andrew, Chen, Zhengjia, Kim, Sungjin, Shin, Dong M, Chen, Zhuo (Georgia)
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22-07-2014
• Subjects: Animals; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Transformation, Neoplastic; Drug Carriers - chemistry; Ferric Compounds - chemistry; Fibronectins - chemistry; Head and Neck Neoplasms - diagnosis; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Indoles - chemistry; Indoles - pharmacokinetics; Indoles - therapeutic use; Integrin beta1 - metabolism; Magnetic Resonance Imaging; Mice; Molecular Targeted Therapy; Nanoparticles; Organosilicon Compounds - chemistry; Organosilicon Compounds - pharmacokinetics; Organosilicon Compounds - therapeutic use; Peptidomimetics - chemistry; Peptidomimetics - metabolism; Photochemotherapy; Squamous Cell Carcinoma of Head and Neck; integrin β1; magnetic resonance imaging; iron-oxide nanoparticle; Fmp-IO-Pc 4; head and neck cancer; photodynamic therapy
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/nn501652j

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.