Characterization and optimization of mTHPP nanoparticles for photodynamic therapy of head and neck cancer

Huiying Ding, Ruben Mora, Jinming Gao, Baran D. Sumer

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objectives. To characterize the properties of polymeric micelles containing different loading percentages of mTHPP, a photosensitizer for photodynamic therapy (PDT), with respect to fluorescence, singlet oxygen ( 1O 2) yield, and in vitro cytotoxicity in head and neck cancer cells. Study Design. Laboratory study. Setting. Polymer chemistry laboratory. Subjects and Methods. Absorption and emission spectroscopy was used to characterize the mTHPP-loaded micelles. The 1O 2 yield was measured to determine the efficiency of reactive oxygen species (ROS) generation. In vitro studies were conducted using the HN5 cells and confirmed with H2009 cells to determine the photodynamic efficacy. DNA assay and confocal microscopy was used to measure intracellular fluorescence. Results. The mTHPP micelles demonstrated the highest fluorescence intensity at 0.5% loading. The 1O 2 generation of the micelles in solution peaked at 2% loading. Phototoxicity and dark toxicity experiments in HN5 and H2009 cells demonstrated that the best therapeutic index was achieved with the 2% loaded micelles with 100% cell cytotoxicity at a micelle concentration of 10 μg/mL and less than 10% dark cytotoxicity. In comparison, 10% loaded micelles demonstrated 100% cell cytotoxicity at a concentration of 20 μg/mL under both light and dark conditions. Confocal microscopy demonstrated increasing intracellular fluorescence with higher loading. Conclusions. The 2% mTHPP-loaded micelles generated greater 1O 2, and 0.5% loading led to the most efficient generation of fluorescence in solution. Higher mTHPP loading density led to increased cellular fluorescence and dark cytotoxicity. Overall, 2% mTHPP-loaded micelles provided the optimal composition for photodynamic therapy with the largest therapeutic window.

Original languageEnglish (US)
Pages (from-to)612-617
Number of pages6
JournalOtolaryngology - Head and Neck Surgery
Volume145
Issue number4
DOIs
StatePublished - Oct 2011

Fingerprint

Photochemotherapy
Micelles
Head and Neck Neoplasms
Nanoparticles
Fluorescence
Confocal Microscopy
Phototoxic Dermatitis
tetra(3-hydroxyphenyl)porphine
Singlet Oxygen
Photosensitizing Agents
Reactive Oxygen Species
Spectrum Analysis
Polymers
Light
DNA
Therapeutics

Keywords

  • Fluorescent surgery
  • Head and neck cancer
  • Nanomedicine
  • Nanoparticles
  • Photodynamic therapy

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Surgery
  • Medicine(all)

Cite this

Characterization and optimization of mTHPP nanoparticles for photodynamic therapy of head and neck cancer. / Ding, Huiying; Mora, Ruben; Gao, Jinming; Sumer, Baran D.

In: Otolaryngology - Head and Neck Surgery, Vol. 145, No. 4, 10.2011, p. 612-617.

Research output: Contribution to journalArticle

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title = "Characterization and optimization of mTHPP nanoparticles for photodynamic therapy of head and neck cancer",
abstract = "Objectives. To characterize the properties of polymeric micelles containing different loading percentages of mTHPP, a photosensitizer for photodynamic therapy (PDT), with respect to fluorescence, singlet oxygen ( 1O 2) yield, and in vitro cytotoxicity in head and neck cancer cells. Study Design. Laboratory study. Setting. Polymer chemistry laboratory. Subjects and Methods. Absorption and emission spectroscopy was used to characterize the mTHPP-loaded micelles. The 1O 2 yield was measured to determine the efficiency of reactive oxygen species (ROS) generation. In vitro studies were conducted using the HN5 cells and confirmed with H2009 cells to determine the photodynamic efficacy. DNA assay and confocal microscopy was used to measure intracellular fluorescence. Results. The mTHPP micelles demonstrated the highest fluorescence intensity at 0.5{\%} loading. The 1O 2 generation of the micelles in solution peaked at 2{\%} loading. Phototoxicity and dark toxicity experiments in HN5 and H2009 cells demonstrated that the best therapeutic index was achieved with the 2{\%} loaded micelles with 100{\%} cell cytotoxicity at a micelle concentration of 10 μg/mL and less than 10{\%} dark cytotoxicity. In comparison, 10{\%} loaded micelles demonstrated 100{\%} cell cytotoxicity at a concentration of 20 μg/mL under both light and dark conditions. Confocal microscopy demonstrated increasing intracellular fluorescence with higher loading. Conclusions. The 2{\%} mTHPP-loaded micelles generated greater 1O 2, and 0.5{\%} loading led to the most efficient generation of fluorescence in solution. Higher mTHPP loading density led to increased cellular fluorescence and dark cytotoxicity. Overall, 2{\%} mTHPP-loaded micelles provided the optimal composition for photodynamic therapy with the largest therapeutic window.",
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AB - Objectives. To characterize the properties of polymeric micelles containing different loading percentages of mTHPP, a photosensitizer for photodynamic therapy (PDT), with respect to fluorescence, singlet oxygen ( 1O 2) yield, and in vitro cytotoxicity in head and neck cancer cells. Study Design. Laboratory study. Setting. Polymer chemistry laboratory. Subjects and Methods. Absorption and emission spectroscopy was used to characterize the mTHPP-loaded micelles. The 1O 2 yield was measured to determine the efficiency of reactive oxygen species (ROS) generation. In vitro studies were conducted using the HN5 cells and confirmed with H2009 cells to determine the photodynamic efficacy. DNA assay and confocal microscopy was used to measure intracellular fluorescence. Results. The mTHPP micelles demonstrated the highest fluorescence intensity at 0.5% loading. The 1O 2 generation of the micelles in solution peaked at 2% loading. Phototoxicity and dark toxicity experiments in HN5 and H2009 cells demonstrated that the best therapeutic index was achieved with the 2% loaded micelles with 100% cell cytotoxicity at a micelle concentration of 10 μg/mL and less than 10% dark cytotoxicity. In comparison, 10% loaded micelles demonstrated 100% cell cytotoxicity at a concentration of 20 μg/mL under both light and dark conditions. Confocal microscopy demonstrated increasing intracellular fluorescence with higher loading. Conclusions. The 2% mTHPP-loaded micelles generated greater 1O 2, and 0.5% loading led to the most efficient generation of fluorescence in solution. Higher mTHPP loading density led to increased cellular fluorescence and dark cytotoxicity. Overall, 2% mTHPP-loaded micelles provided the optimal composition for photodynamic therapy with the largest therapeutic window.

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