NDLI: A Cell-targeted Photodynamic Nanomedicine Strategy for Head & Neck Cancers

Content Provider	PubMed Central
Author	Master, Alyssa Malamas, Anthony Solanki, Rachna Clausen, Dana M. Eiseman, Julie L. Gupta, Anirban Sen
Abstract	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 intra-tumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas.
Related Links	http://dx.doi.org/10.1021/mp400007k
Ending Page	1997
Page Count	10
Starting Page	1988
File Format	PDF
ISSN	15438384
e-ISSN	15438392
Journal	Molecular pharmaceutics
Issue Number	5
Volume Number	10
Language	English
Publisher Date	2013-05-06
Access Restriction	Open
Subject Keyword	Molecular Medicine Drug Discovery Pharmaceutical Science Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Molecular Medicine Pharmaceutical Science

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