Photodynamic Tumor Eradication With a Novel Targetable Photosensitizer: Strong Vascular Effects and Dependence on Treatment RepetitionVersusPotentiation
| Autor: | Dagmar Högemann Savellano, Mark D. Savellano, Tanay Ganga, Nicci Owusu-Brackett, Nadia L. Leung, Ji Son |
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| Rok vydání: | 2012 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
Immunoconjugates Porphyrins Light Combination therapy medicine.medical_treatment Cetuximab Mice Nude Photodynamic therapy Pharmacology Antibodies Monoclonal Humanized Biochemistry Drug Administration Schedule Mice Growth factor receptor Cell Line Tumor medicine Animals Humans Photosensitizer Physical and Theoretical Chemistry Fluorescent Dyes Photosensitizing Agents Vulvar Neoplasms Chemistry Optical Imaging Dipeptides General Medicine In vitro Tumor Burden Immunoconjugate Photochemotherapy Doxorubicin Carcinoma Squamous Cell Drug Therapy Combination Female Neoplasm Transplantation medicine.drug |
| Zdroj: | Photochemistry and Photobiology. 89:687-697 |
| ISSN: | 0031-8655 |
| Popis: | A novel pyropheophorbide-a (PPa) derivative, Ac-sPPp, was developed in our lab for targeted photodynamic therapy (PDT) and combination therapies. Its versatile peptide moiety, high water-solubility, amphiphilicity, and micellar aggregation allow efficient coupling to targeting moieties and convenient mixing with other therapeutics. Photosensitizer immunoconjugate (PIC) targeted PDT, using Ac-sPPp conjugated to therapeutic anti-epidermal growth factor receptor (EGFR) antibody cetuximab, and PDT + chemotherapy combination treatment, using Ac-sPPp mixed with stealth liposomal doxorubicin (Doxil), were investigated as promising strategies for potentiating PDT and improving target specificity. Passively targeted PDT with Ac-sPPp only or surfactant-solubilized PPa was also investigated for comparison. The A-431 human vulvar squamous cell carcinoma, xenografted in nude mice, was chosen as a tumor model because of its high EGFR expression and sensitivity to liposomal doxorubicin in vitro. Fluorescence imaging and PDT experiments showed that Ac-sPPp formulations circulated far longer and provided superior tumor contrast and superior tumor control compared to PPa. Strong PDT vascular effects were observed by laser Doppler imaging regardless of whether Ac-sPPp was passively or actively targeted. Passively targeted Ac-sPPp PDT gave equivalent or better tumor control than PIC-targeted PDT or PDT + Doxil combination therapy, and when treatments were repeated, it also yielded the highest cure rate. |
| Databáze: | OpenAIRE |
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