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.

Efficacy of photochemical internalisation using disulfonated chlorin and porphyrin photosensitisers: An in vitro study in 2D and 3D prostate cancer models

“…PDT and the application of the cytotoxin), and % V in the denominator is the percentage viability observed following the PCI combination treatment [25], [26]. If α > 1 then a synergistic effect has been observed whereas an antagonistic effect is denoted by α < 1.…”

“…If α > 1 then a synergistic effect has been observed whereas an antagonistic effect is denoted by α < 1. Τhis analysis has been used previously by others to identify synergistic effects in PCI [26].…”

Photochemical internalization enhanced macrophage delivered chemotherapy

“…Additionally, AlS 2 Pc-mediated PDT has been shown to enhance the effects of DOX on mice bearing murine leukemia and lymphoma compared to chemotherapy alone [20]. In contrast to these results, the combination of PDT and DOX was only additive on DOX sensitive MCF-7 human breast cancer cells assayed by either MTT or colony inhibition assays [17,21]. Based on its water solubility and molecular weight (580 g/mol), one would expect the effects of DOX to be enhanced in a PCI protocol, as was observed with the F98 glioma cell line used in the present work.…”

Nanoparticle-Mediated Drug Delivery for Treating Melanoma

“…PCI has been extensively studied for cytosolic delivery of toxins, oligonucleotides, weakly basic drugs like DOX and cisplatin and can be therapeutically exploited for overcoming resistance by efflux transporters as well as intracellular sequesterization of drugs [166–168]. Light-mediated activation of endocytosed amphiphillic photosensitizer generates reactive oxygen species which damage membrane of endocytic vesicles and thereby lead to cytosolic delivery of therapeutic agent.…”