Photodynamic therapy as an effective therapeutic approach in MAME models of inflammatory breast cancer

Abstract

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/cm2. 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/cm2 for each agent resulted in >90 % cell death, a response only achieved by BPD–PDT at a dose of 360 mJ/cm2. 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.

High Aspect Ratio Nanotubes Formed by Tobacco Mosaic Virus for Delivery of Photodynamic Agents Targeting Melanoma

“…The development pipeline is rapidly expanding with numerous clinical and preclinical trials investigating novel photosensitizers and their use in PDT targeting various cancers. These include head and neck, skin, cervical, lung, gastric, prostate, and breast cancers. ,− …”

Photodynamic therapy: Promotion of efficacy by a sequential protocol

“…This effect could be reproduced in a cell-culture system using any of three lysosomal-targeting agents [25]. Another report indicated successful promotion of photokilling by this model in a 3D cell-culture model of inflammatory breast cancer [26]. …”

Interaction of prostate carcinoma-associated fibroblasts with human epithelial cell lines in vivo

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