Phenotypically Screened Carbon Nanoparticles for Enhanced Combinatorial Therapy in Triple Negative Breast Cancer

• Published in: Cellular and molecular bioengineering 2017-10, Vol.10 (5), p.371-386
• Main Authors: Kampert, Taylor, Misra, Santosh K., Srivastava, Indrajit, Tripathi, Indu, Pan, Dipanjan
• Format: Article
• Language: English
• Subjects: Biological and Medical Physics; Biomaterials; Biomedical Engineering and Bioengineering; Biomedical Engineering/Biotechnology; Biophysics; Breast cancer; Cancer; Carbon; Cell Biology; Clathrin; Combinatorial analysis; Drug delivery systems; Drug resistance; Dynamin; Engineering; High resistance; In vitro methods and tests; Mesenchyme; Nanoparticles; NF-κB protein; Phospholipids; Stat3 protein; Synergistic effect
• ISSN: 1865-5025; 1865-5033
• DOI: 10.1007/s12195-017-0490-y

Introduction Triple negative breast cancer (TNBC) is a highly aggressive type of breast cancer with high resistance to current standard therapies. We demonstrate that phenotypically stratified carbon nanoparticle is highly effective in delivering a novel combinatorial triple drug formulation for synergistic regression of TNBC in vitro and in vivo . Method The combinatorial formulation is comprised of repurposed inhibitors of STAT3 (nifuroxazide), topoisomerase-II-activation-pathway (amonafide) and NFκb (pentoxifylline). Synergistic effect of drug combination was established in a panel of TNBC-lines comprising mesenchymal-stem-like, mesenchymal and basal-like cells along with non-TNBC-cells. The delivery of combinatorial drug formulation was achieved using a phenotypically screened carbon nanoparticles for TNBC cell lines. Results Results indicated a remarkable five-fold improvement (IC50-6.75  µ M) from the parent drugs with a combinatorial index