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Nanoparticle delivery of HIF1? siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.

ABSTRACT: Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1? siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1? siRNA nanoparticles effectively reduced HIF1? expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Intravenous injection of the same nanoparticles into human SCC4 or SAS xenografted mice likewise resulted in concentrated siRNA accumulation and reduced HIF1? expression in tumor tissues. When combined with photodynamic therapy, HIF1? siRNA nanoparticles enhanced the regression in tumor size resulting in a?~40% decrease in volume after 10 days. Combination therapy was found to be substantially more effective than either HIF1? siRNA or photodynamic therapy alone. Results from caspase-3, TUNEL, and CD31 marker studies support this conclusion. Our results show the potential use of LCP nanoparticles for efficient delivery of HIF1? siRNA into tumors as part of combination therapy along with PDT in the treatment of oral squamous cell carcinoma.

SUBMITTER: Chen WH

PROVIDER: S-EPMC5010227 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.

Chen Wei-Hua WH Lecaros Rumwald Leo G RL Tseng Yu-Cheng YC Huang Leaf L Hsu Yih-Chih YC

Cancer letters 20150114 1

Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1α siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1α siRNA nanoparticles effectively reduced HIF1α expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Intravenou ...[more]

PMID: 25596376

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Project description:Fluorescence image-guided surgery (IGS) using antibody conjugates of the fluorophore IRDye800CW have revolutionized the surgical debulking of tumors. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, conjugated to IRDye800CW (Cet-IRDye800) is the first molecular targeted antibody probe to be used for IGS in head and neck cancer patients. In addition to surgical debulking, Cetuximab-targeted photodynamic therapy (photoimmunotherapy; PIT) is emerging in the clinic as a powerful modality for head and neck tumor photodestruction. A plethora of other photoactivable agents are also in clinical trials for photodynamic-based therapies of head and neck cancer. Considering the vascular and stromal modulating effects of sub-therapeutic photodynamic therapy, namely photodynamic priming (PDP), this study explores the potential synergy between PDP and IGS for a novel photodynamic image-guided surgery (P-IGS) strategy. To the best of our knowledge, this is the first demonstration that PDP of the tumor microenvironment can augment the tumor delivery of full-length antibodies, namely Cet-IRDye800. In this study, we demonstrate a proof-of-concept that PDP primes orthotopic FaDu human head and neck tumors in mice for P-IGS by increasing the delivery of Cet-IRDye800 by up to 138.6%, by expediting its interstitial accumulation by 10.5-fold, and by increasing its fractional tumor coverage by 49.5% at 1 h following Cet-IRDye800 administration. Importantly, PDP improves the diagnostic accuracy of tumor detection by up to 264.2% with respect to vicinal salivary glands at 1 h. As such, PDP provides a time-to-surgery benefit by reducing the time to plateau 10-fold from 25.7 h to 2.5 h. We therefore propose that a pre-operative PDP regimen can expedite and augment the accuracy of IGS-mediated surgical debulking of head and neck tumors and reduce the time-to-IGS. Furthermore, this P-IGS regimen, can also enable a forward-looking post-operative protocol for the photodestruction of unresectable microscopic disease in the surgical bed. Beyond this scope, the role of PDP in the homogenous delivery of diagnostic, theranostic and therapeutic antibodies in solid tumors is of considerable significance to the wider community.

Dataset Information

Nanoparticle delivery of HIF1? siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.

Publications

Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.

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