title: Photochemical internalization-mediated delivery of chemotherapeutic agents in human breast tumor cell lines.
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.
authors.affiliation: Department of Neurological Surgery, University of California Irvine, Orange, CA, USA. marlonmathews@yahoo.com
authors.forename: Marlon S
authors.initials: MS
authors.lastname: Mathews
authors.forename: Van
authors.initials: V
authors.lastname: Vo
authors.forename: En-Chung
authors.initials: EC
authors.lastname: Shih
authors.forename: Genesis
authors.initials: G
authors.lastname: Zamora
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Sun
authors.forename: Steen J
authors.initials: SJ
authors.lastname: Madsen
authors.forename: Henry
authors.initials: H
authors.lastname: Hirschberg
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001761:Bleomycin / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D054023:Lasers, Semiconductor; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D001761:Bleomycin; C064331:aluminum phthalocyanine disulfonate; D004317:Doxorubicin; D002945:Cisplatin