Juliane Hopf1 Paul Helquist1 Gary Bernstein1 Prakash Nallathamby1

1, Univ of Notre Dame, Notre Dame, Indiana, United States

Development of new cancer therapies rely on investigation of new drug classes to exploit cellular targets that may be used in single-agent or combination therapy and selective delivery of drugs to tumors. NDnano has developed magnetoelectric nanoparticles (ME-NPs) loaded with drugs that can be spatially directed to specifically penetrate malignant cells while sparing normal tissues. This approach not only expands the arsenal of single agents available to the clinical oncologist but also broadens the scope of combination therapy.
Combination therapy is critical for dealing with drug resistance mechanisms and multiple cancer cell mutations that typify difficult to treat tumors. In this study, we loaded potent inhibitors of vacuolar ATPase (V-ATPase) along with standard chemotherapeutics such as paclitaxel to specifically target metastatic breast cancer cells. Metastasis of breast cancer cells results in >50% fatalities. V-ATPase proton pumps have been directly implicated in aiding metastasis. V-ATPase and cancer cell-specific isoforms are overexpressed in many tumor types and are involved in cellular signaling, membrane trafficking, cancer cell survival, cell migration, cell invasiveness, metastasis, and drug resistance. Thus, the hypothesis is that the multidrug carrying ME-NPs will target the primary tumor with standard chemotherapeutics and simultaneously prevent metastasis by inhibiting the proton pumps, thus improving the overall prognosis. Additionally, using targeted ME-NPs mitigates the debilitating side-effects of current chemotherapeutic regimens by using the ME-NPs as a nanocarrier for delivering low doses of therapeutics with increased accumulation of the therapeutics at the tumor site through magnetic field guidance.
In this abstract we will (a) discuss the synthesis and conjugation of multiple therapeutics to ME-NPs; (b) discuss multiple modes of drug delivery from the ME-NPs (ON-Demand, stimuli dependent, enzymatic release, etc.) and (c) in vitro cell and in vivo mouse studies that show selective targeting of ME-NPs to metastatic MDAMB-231 breast cancer cell and improved survivability in the sample group.