John Garner

PLA from PolySciTech used in development of nanoparticle-based triple-negative breast cancer therapy

Blog Post created by John Garner on Nov 15, 2017

Zhou, 2017 Gefitinib polyscitech cancer.JPG

Most forms of breast cancer respond well to conventional therapies, such as doxorubicin. There is, however, a specific type of breast cancer that is referred to as ‘triple-negative’ (named this because it does not have receptors for estrogen, progesterone, or HER2) breast cancer. It is highly resistant to conventional chemotherapy and very invasive. Recently, researchers at University of Cincinnati utilized polylactide (AP128) from PolySciTech (www.polyscitech.com) to develop chemotherapy particles which released gefitinib followed by sequential release of doxorubicin. These particles were found to be significantly more effective at treating triple-negative breast cancer than . This research holds promise for developing more effective chemotherapy strategies to treat breast cancer. Read more: Zhou, Zilan, Mina Jafari, Vishnu Sriram, Jinsoo Kim, Joo-Youp Lee, Sasha J. Ruiz-Torres, and Susan E. Waltz. "Delayed Sequential Co-Delivery of Gefitinib and Doxorubicin for Targeted Combination Chemotherapy." Molecular Pharmaceutics (2017). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00669

“There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal growth factor receptor (EGFR) signaling applicable for the treatment of triple negative breast cancers. To realize this nanoparticle design, Gi complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(l-lactide)-block-polyethylene glycol (PLA-b-PEG) and with an encapsulation efficiency of ∼90%. The nanoparticle system exhibited a desired sequential release of Gi followed by Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated approximate 4-fold and 3-fold increases in anticancer efficacy compared to a control group of Dox–PLA-PEG conjugate against MDA-MB-468 and A549 cell lines in terms of half maximal inhibitory concentration (IC50), respectively. High tumor accumulation of the nanoparticle system was also substantiated for potential in vivo applicability by noninvasive fluorescent imaging. Keywords: combination therapy; controlled delivery; doxorubicin; EGFR inhibitor; nanoparticles; sequential delivery”

Outcomes