PLGA-PEG-Mal, PLGA-CY5 from PolySciTech used in development of triple-negative breast-cancer targeting nanoparticles

 

Cancer is a widely diverse set of disease states with a single moniker to describe, in general, any overgrowth of human tissue. Because of their diversity, the method to treat the cancer must be optimized to the exact type of cancer. Most types of breast cancer respond well to modern therapy based on their specific markers. For example, most HER2+ type breast cancers respond well to treatments utilizing herceptin which targets the HER2 receptor. However, a form of breast cancer which lacks the three most common receptors, so called “triple-negative” breast cancer is very difficult to treat as these conventional therapies are ineffective to that particular type of cancer. Recently, researchers at University of Maryland utilized Methoxy-terminated PLGA−PEG (10:5 kDa) (Cat# AK010), PLGA−PEG with maleimide end group (PLGA−PEGMal, 10:5 kDa) (Cat# AI053), and PLGA-Cyanine 5 (PLGA-Cy5, 30−55 kDa) (Cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create fn-14 targeted nanoparticles for therapy against triple-negative breast cancer that has metastasized into the brain. This research holds promise to improve therapies against this very difficult to treat form of cancer. Read more: Carney, Christine P., Anshika Kapur, Pavlos Anastasiadis, Rodney M. Ritzel, Chixiang Chen, Graeme F. Woodworth, Jeffrey A. Winkles, and Anthony J. Kim. "Fn14-Directed DART Nanoparticles Selectively Target Neoplastic Cells in Preclinical Models of Triple-Negative Breast Cancer Brain Metastasis." Molecular Pharmaceutics (2022). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.2c00663

“Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA–PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane─an FDA-approved paclitaxel nanoformulation─following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association with Fn14-positive human and murine TNBC cell lines cultured in vitro. We next identified tumor cells as the predominant source of Fn14 expression in the TNBC BM-immune microenvironment with minimal expression by microglia, infiltrating macrophages, monocytes, or lymphocytes. We then show that despite similar accumulation in brains harboring TNBC tumors, Fn14-targeted DARTs exhibit significant and specific association with Fn14-positive TNBC cells compared to nontargeted NPs or Abraxane. Together, these results indicate that Fn14 expression primarily by tumor cells in TNBC BMs enables selective DART NP delivery to these cells, likely driving the significantly improved therapeutic efficacy observed in our prior work.”