A Cell-Targeted Photodynamic Nanomedicine Strategy for Head and Neck Cancers

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.

Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

“…3). Receptor-mediated active internalization of the particles is triggered by binding of the vehicle surface decoration of the GE11 peptides to EGFR, which is highly expressed on the surfaces of head and neck cancer cells [17]. This is consistent with a previous report showing that the peptide GE11 may be able to mediate the target-specific delivery of reporter genes to EGFR-overexpressing tumor cells in vitro [7].…”

EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization andin vitroevaluation

“…The mechanism of targeted micelles uptake is known to be via the receptor/ substrate internalization process. Receptor-mediated active internalization of the micelles is triggered by the binding of the vehicle surface decoration of GE11 peptides to the high EGFR expression on the surface of other head and neck cancers cells (Master et al, 2013). In this study, GE11-modified micelles did not show obvious difference in EGFRlow expressed U-937 cells.…”

Triple-responsive expansile nanogel for tumor and mitochondria targeted photosensitizer delivery

“…Since EGFR is overexpressed in most HNSCC, Master et al functionalized PCL-PEG micelles with a EGFR targeting peptide, GE11. With the help of GE11, the targeted micelles exhibited higher cellular uptake and cell killing effect than the non-targeted ones [30]. Though, the high skin Pc 4 retention issue remaining unaddressed.…”