Photodynamic therapy as an effective therapeutic approach in MAME models of inflammatory breast cancer.
Photodynamic therapy (PDT) is a minimally invasive, FDA-approved therapy for treatment of endobronchial and esophageal cancers that are accessible to light. Inflammatory breast cancer (IBC) is an aggressive and highly metastatic form of breast cancer that spreads to dermal lymphatics, a site that would be accessible to light. IBC patients have a relatively poor survival rate due to lack of targeted therapies. The use of PDT is underexplored for breast cancers but has been proposed for treatment of subtypes for which a targeted therapy is unavailable. We optimized and used a 3D mammary architecture and microenvironment engineering (MAME) model of IBC to examine the effects of PDT using two treatment protocols. The first protocol used benzoporphyrin derivative monoacid A (BPD) activated at doses ranging from 45 to 540 mJ/cm(2). The second PDT protocol used two photosensitizers: mono-L-aspartyl chlorin e6 (NPe6) and BPD that were sequentially activated. Photokilling by PDT was assessed by live-dead assays. Using a MAME model of IBC, we have shown a significant dose-response in photokilling by BPD-PDT. Sequential activation of NPe6 followed by BPD is more effective in photokilling of tumor cells than BPD alone. Sequential activation at light doses of 45 mJ/cm(2) for each agent resulted in >90 % cell death, a response only achieved by BPD-PDT at a dose of 360 mJ/cm(2). Our data also show that effects of PDT on a volumetric measurement of 3D MAME structures reflect efficacy of PDT treatment. Our study is the first to demonstrate the potential of PDT for treating IBC.
Department of Physiology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI, 48201, USA. naggarwa@med.wayne.edu.
Neha
N
Aggarwal
Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI, 48201, USA. asandago@med.wayne.edu.
Ann Marie
AM
Santiago
Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI, 48201, USA. dhkessel@med.wayne.edu.
David
D
Kessel
Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI, 48201, USA. bsloane@med.wayne.edu.|Department of Oncology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI, 48201, USA. bsloane@med.wayne.edu.
Bonnie F
BF
Sloane
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D058922:Inflammatory Breast Neoplasms / Q000473:pathology* / Q000628:therapy; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D046509:Tissue Culture Techniques; D059016:Tumor Microenvironment
D017319:Photosensitizing Agents; D053148:Caspase 3
3D; Inflammatory breast cancer; MAME cultures; Photodynamic therapy