A Potential New Approach to Breast Cancer Tumor Targeting is the Monthly Publication Highlight

September 24, 2015

A multidisciplinary collaborative effort across six colleges and two universities that describes the use of a novel three dimensional tumor model for triple negative breast cancer (TNBC) for investigating a radiation enhanced nanoparticle dual-drug delivery system is the UK College of Pharmacy Research Publication Highlight for August 2015.

The article was published in Nanomedicine: Nanotechnology, Biology and Medicine and is entitled “3D Tumor Tissue Analogs and Their Orthotopic Implants for Understanding Tumor-Targeting of Microenvironment-Responsive Nanosized Chemotherapy and Radiation.”

The project was directed by Dr. Meenakshi Upreti, an Assistant Professor of Pharmaceutical Sciences at UK’s College of Pharmacy. Pallavi Sethi, a postdoctoral fellow in the Upreti Laboratory, was the first author of the study. Postdoctoral fellow Amar Jyoti and PharmD student Ryan Chan, also from the Upreti laboratory, contributed to this study. Dr. Thomas O’Halloran, Professor of Chemistry, and Elden Swindell, postdoctoral fellow in Chemical Engineering from the O’Halloran Laboratory at Northwestern University contributed to the nanoparticle design and preparation. In addition, Dr. Urlich Langer now in the University of Maryland and Dr. Jonathan Feddock, at UK’s Colleges of Medicine provided expertise in Radiation Medicine. Expertise in informatics was provided by Dr. Radhakrishnan Nagarajan from UK’s College of Public Health.

A major hurdle in the translation of novel therapeutic approaches to fight cancer in clinical practice is the ability to mimic the complex environment of the tumor in patients. This has led to the development of a number of three dimensional tumor models attempting to mimic the tumor “microenvironment” that not only alters the cellular physiology of the tumor cells, but also their response to anti-cancer drugs.

In this study, members of the Upreti laboratory and her collaborators, have developed an innovative system to co-culture fluorescent color-coded murine cell types that exist in the tumor microenvironment in three dimension to form ‘tumor tissue analogs’ (TTA). When implanted in vivo, these TTA more closely represented the growth, metastasis and drug uptake in human tumors in contrast to the traditional tumor models for TNBC. In the second phase of the study, the team used the 3D tumor model to understand a radiation enhanced targeted delivery of dual-drug loaded nanoparticles to the TNBC microenvironment. This nanotherapeutic strategy was designed to sensitize and eliminate the tumor cells by targeting the tumor microenvironment, thereby increasing the therapeutic efficacy of the anti-tumor strategy in selective and effective inhibition of tumor growth and metastasis in contrast to the conventional systemic approaches.

“This work is multifaceted and highly-significant because it not only establishes a novel 3D model for evaluating chemotherapeutics, but also demonstrates how drugs behave differently in the body due to tumor complexity. Further, it suggests that these properties may be exploited in the development of new approaches to tumor targeting,” said Greg Graf, Assistant Dean for Translational Research.