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Journal of Environmental Pathology, Toxicology and Oncology

Impact factor: 1.246

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v31.i1.60
pages 49-59

Photochemical Internalization-Mediated Delivery of Chemotherapeutic Agents in Human Breast Tumor Cell Lines

Marlon S. Mathews
Department of Neurological Surgery, University of California Irvine, Orange, CA ; Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, CA
Van Vo
Department of Health Physics, University of Nevada, Las Vegas, NV
En-Chung Shih
Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, CA
Genesis Zamora
Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA 92612
Chung-Ho Sun
Beckman Laser Institute, University of California, 1002 Health Science Road, East Irvine, CA 92612
Steen J. Madsen
Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, NV 89154
Henry Hirschberg
Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, NV 89154; Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA 92612

ABSTRACT

Breast-conservation surgery (BCS) is now utilized in patients with stage I and II invasive breast cancer. However, positive surgical margins are associated with recurrence, and therefore some form of localized postoperative therapy (radiation/chemotherapy) is necessary to eliminate remaining cancer cells. Existing modalities have significant treatment-limiting side effects; therefore, alternative forms of localized therapy need to be explored. We studied the ex vivo effects of photochemical internalization (PCI) using 4 chemotherapeutic agents: cisplatin, cisplatin analog [D prostanoid, DP], doxorubicin, and bleomycin) on 3 breast cancer cell lines: MCF-7, MDA-MB-435, and MDA-MB-231. Illumination was carried out using a 670-nm diode laser at 5 mW/cm2 following incubation in the photosensitizer with aluminum phthalocyanine disulfonate. Toxicity was investigated using colony-forming assays and the mechanism of cell death was determined using Annexin flow-cytometry. We found that toxicity of DP and bleomycin was significantly enhanced by PCI compared with drug alone but was unchanged for cisplatin and doxorubicin. PCI treatment caused a decrease in the percentage of viable cells, predominantly by enhancing apoptosis. The action was synergistic across all 3 cell lines tested for DP and bleomycin. Thus, with appropriate delivery devices and choice of chemotherapeutic agents, PCI holds the promise of enhancing tumor cell toxicity surrounding the cavity of BCS resection sites and thereby decreasing local recurrence.