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

Dongsheng Wang, Baowei Fei, Luma V. Halig, Xulei Qin, Zhongliang Hu, Hong Xu, Yongqiang Andrew Wang, Zhengjia Chen, Sungjin Kim, Dong M. Shin, Zhuo Chen

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6620-6632
Number of pages13
JournalACS Nano
Volume8
Issue number7
DOIs
StatePublished - Jul 22 2014
Externally publishedYes

Fingerprint

Photodynamic therapy
Iron oxides
iron oxides
therapy
cancer
Nanoparticles
Imaging techniques
nanoparticles
Fibronectins
Peptides
peptides
chemotherapy
Tumors
tumors
Heterografts
toxicity
Pharmaceutical Preparations
Toxicity
ferric oxide
Ligands

Keywords

  • Fmp-IO-Pc 4
  • head and neck cancer
  • integrin β1
  • iron-oxide nanoparticle
  • magnetic resonance imaging
  • photodynamic therapy

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

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

In: ACS Nano, Vol. 8, No. 7, 22.07.2014, p. 6620-6632.

Research output: Contribution to journalArticle

Wang, D, Fei, B, Halig, LV, Qin, X, Hu, Z, Xu, H, Wang, YA, Chen, Z, Kim, S, Shin, DM & Chen, Z 2014, 'Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer', ACS Nano, vol. 8, no. 7, pp. 6620-6632. https://doi.org/10.1021/nn501652j
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. / Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer. In: ACS Nano. 2014 ; Vol. 8, No. 7. pp. 6620-6632.
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AU - Wang, Yongqiang Andrew

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AB - 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.

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