Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers

Author

Neha Aggarwal, Wayne State UniversityFollow

Access Type

Open Access Dissertation

Date of Award

January 2015

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Physiology

First Advisor

Bonnie F. Sloane

Second Advisor

Douglas Yingst

Abstract

Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for

treatment of several indications including endobronchial and esophageal cancers that are

accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)

are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal

lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients

have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is

underexplored for breast cancers but has been proposed for treatment of subtypes for which a

targeted therapy is unavailable.

Methods: We optimized and used a mammary architecture and microenvironment engineering

(MAME) model of IBC to examine the effects of PDT using two treatment protocols. The first

protocol used the benzoporphyrin derivative monoacid A (BPD) activated at doses ranging from

45 mJ/cm2 to 540 mJ/cm2. The second PDT protocol used two photosensitizers: BPD and mono-

L-aspartyl chlorin e6 (NPe6), which were sequentially activated. Effects of PDT were assessed

by live-dead assays.

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Results: Using a MAME model of TNBC and IBC, we demonstrate a significant dose-response

in photokilling by BPD-PDT. We found that sequential activation of NPe6 followed by BPD is

more effective in photokilling of tumor cells than is BPD alone. Sequential activation at a dose

of 45 mJ/cm2 each resulted in >90% cell death, a response only achieved by BPD-PDT at a dose

of 360 mJ/cm2. Furthermore, our data show that volumetric measurement of 3D MAME

structures reflect efficacy of PDT treatment. We also show that the mechanism of cell death

after sequential activation of NPe6 followed by BPD is apoptosis.

Conclusion: Our study is the first to demonstrate the potential of PDT in treating MAME

structures of TNBC and IBC.

Recommended Citation

Aggarwal, Neha, "Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers" (2015). Wayne State University Dissertations. 1328.
https://digitalcommons.wayne.edu/oa_dissertations/1328