Radiology & Novel Cancer Therapies

Biography

Biography: Alexandria DeCarlo

Abstract

The current clinical approach for cancer treatment broadly targets proliferating malignant cells. This treatment also affects healthy cells. It is essential to develop a highly specific chemotherapy drug carrier which targets explicitly only cancerous cells. We have previously reported on a pH-responsive folic acid (FA)-functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the requisite features for efficient drug delivery specifically targeting the overexpression of the folic acid receptor alpha (FRa) on cancer cells and tumor spheroids. Interestingly, we reported that the empty FA-DABA-SMA nanoparticle also decreased spheroid volume revealing a previously unknown intracellular mechanism of action of the nanopolymer. Reports have shown that FRa can act as a transcription factor responsible for transcribing DNA repair enzymes. We propose that the FA-DABA-SMA binds to the FRa and is transported into the cell towards the nucleus where, due to its large size, directly interferes with the binding of transcription factors, and thus reducing cancer cell viability. Through the use of immunocytochemistry, fluorescent microscopy, and WST-1 proliferation assays, preliminary results suggest that the empty FA-DABA-SMA is internalized and brought to the nucleus within 48 hours where it begins to exert its effect. These results provide valuable insights into the mechanism(s) of smart delivery systems allowing for a new generation of treatments to increase specificity and reduce systemic toxicity. This novel targeting delivery system may overcome many of the cytotoxic effects experienced by patients receiving chemotherapy. These results reveal the dual actions of the smart functionalized nanocarrier, showing that this novel drug delivery system is an effective and potent delivery system specifically targeting cancer cells.