Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer.

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.

• Authors: Dongsheng Wang, Baowei Fei, Luma V Halig, Xulei Qin, Zhongliang Hu, Hong Xu, Yongqiang Andrew Wang, Zhengjia Chen, Sungjin Kim, Dong M Shin, Zhuo Georgia Chen
• Journal: ACS nano (ACS Nano) Vol. 8 Issue 7 Pg. 6620-32 (Jul 22 2014) ISSN: 1936-086X [Electronic] United States
• PMID: 24923902 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• Ferric Compounds
• Fibronectins
• Indoles
• Integrin beta1
• Organosilicon Compounds
• Peptidomimetics
• silicon phthalocyanine
• ferric oxide

Topics

• Animals
• Carcinoma, Squamous Cell (diagnosis, drug therapy, metabolism, pathology)
• Cell Transformation, Neoplastic
• Drug Carriers (chemistry)
• Ferric Compounds (chemistry)
• Fibronectins (chemistry)
• Head and Neck Neoplasms (diagnosis, drug therapy, metabolism, pathology)
• Humans
• Indoles (chemistry, pharmacokinetics, therapeutic use)
• Integrin beta1 (metabolism)
• Magnetic Resonance Imaging
• Mice
• Molecular Targeted Therapy
• Nanoparticles
• Organosilicon Compounds (chemistry, pharmacokinetics, therapeutic use)
• Peptidomimetics (chemistry, metabolism)
• Photochemotherapy
• Squamous Cell Carcinoma of Head and Neck