title: 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 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.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Blvd, Cleveland, Ohio 44106, United States.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Master
authors.forename: Anthony
authors.initials: A
authors.lastname: Malamas
authors.forename: Rachna
authors.initials: R
authors.lastname: Solanki
authors.forename: Dana M
authors.initials: DM
authors.lastname: Clausen
authors.forename: Julie L
authors.initials: JL
authors.lastname: Eiseman
authors.forename: Anirban
authors.initials: A
authors.lastname: Sen Gupta
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D016513:Mice, SCID; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage; D017646:Organosilicon Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; C082854:silicon phthalocyanine; C512478:EGFR protein, human; D066246:ErbB Receptors