Document Detail

A cell-targeted photodynamic nanomedicine strategy for head and neck cancers.
MedLine Citation:
PMID:  23531079     Owner:  NLM     Status:  MEDLINE    
Photodynamic therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. To this end, we report on a cell-targeted nanomedicine approach for the photosensitizer silicon phthalocyanine-4 (Pc 4), by packaging it within polymeric micelles that are surface-decorated with GE11-peptides to promote enhanced cell-selective binding and receptor-mediated internalization in EGFR-overexpressing H&N cancer cells. Using fluorescence spectroscopy and confocal microscopy, we demonstrate in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N SCC-15 cells. We further demonstrate that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, we demonstrate that the EGFR-targeted Pc 4-nanoformulation results in significant intratumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise toward a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas.
Alyssa Master; Anthony Malamas; Rachna Solanki; Dana M Clausen; Julie L Eiseman; Anirban Sen Gupta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-04-24
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  10     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-06     Completed Date:  2013-12-16     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1988-97     Citation Subset:  IM    
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MeSH Terms
Biological Transport, Active
Carcinoma, Squamous Cell / drug therapy*,  metabolism,  pathology
Cell Line, Tumor
Chemistry, Pharmaceutical
Drug Delivery Systems
Head and Neck Neoplasms / drug therapy*,  metabolism,  pathology
Indoles / administration & dosage,  pharmacokinetics
Mice, SCID
Nanomedicine / methods
Nanoparticles / administration & dosage
Organosilicon Compounds / administration & dosage,  pharmacokinetics
Photochemotherapy / methods*
Photosensitizing Agents / administration & dosage,  pharmacokinetics
Receptor, Epidermal Growth Factor / metabolism
Tumor Stem Cell Assay
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/Indoles; 0/Organosilicon Compounds; 0/Photosensitizing Agents; 135719-28-7/silicon phthalocyanine; EC protein, human; EC, Epidermal Growth Factor

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