Patrick J Sinko
Rutgers, The State University of New Jersey, USA
Title: Nanotechnology approaches for intensifying localized combination therapy for precision treatment of early stage breast cancer
Biography
Biography: Patrick J Sinko
Abstract
Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer (BC) with possible microinvasions into the breast stroma. DCIS accounts for more than 16% of new BC diagnoses in women. DCIS progresses to Invasive Ductal Carcinoma (IDC) over time in 39-53% of patients, if left untreated. The vast majority of BC cases originate in the mammary duct. In this presentation, a nanoscale delivery system will be described that utilizes transpapillary delivery to achieve molecularly targeted, pathway-specific therapy in cancerous areas of the mammary duct. Our preliminary results with a nanosuspension of ciclopirox (CPX) in an orthotopic model of BC established the concept that sustained ductal exposure could completely suppress BC occurrence in vivo. For these studies polymeric NPs (nanoparticles) as well as lipid-polymer hybrid (LPH) NPs were the primary delivery vehicles. In order to achieve sustained precision treatment, HER2, transferrin receptor and/or EGFR were targeted using peptide ligands covalently bound to the surface of NPs. Ligand surface densities of 5% and 10% were evaluated and it was found that surface functionalized NPs enhanced binding and uptake into target cells. Cytoxicity was significantly increased with EGFR or TfR targeted NPs as compared to CPX alone or non functionalized CPX-loaded NPs. A synergistic effect was observed when CPX was administered with gedatolisib, a PI3K/Akt/mTOR inhibitor resulting in a dose reduction index of ~6. In addition, the treatments were effective not only in BC cells but also cancer stem-like cells. Our efforts in addition to describing these studies and results, the engineering of the NPs to enhance ductal retention and specificity will also be described.