Cancer Nanotechnology: From Expansile Nanoparticles for Treatment to SiN Nanopores for Diagnosis

Cancer Nanotechnology: From Expansile Nanoparticles for Treatment to SiN Nanopores for Diagnosis

Nanoparticle drug delivery systems afford researchers the ability to increase drug solubility, alter pharmacokinetics, target specific locations in the body, provide controlled release of a drug and thereby improve drug efficacy while limiting systemic side effects.  We have developed unique pH-responsive drug-loaded expansile nanoparticles (eNPs) that localize to tumors, traffic through the lymphatic system, swell to release drug once inside the cell, and provide a depot for prolong exposure of the cell to the drug. In this presentation, I will discuss the mechanism of action and performance of paclitaxel loaded eNPs in an intraperitoneal mesothelioma. The synthesis of the eNPs is described first followed by several particle characterization techniques, including qNano, DLS, SEM, and TEM that measure particle size as a function of pH and swelling time.  We next quantify the unique ability of drug-loaded eNPs to act as drug depots for paclitaxel within the cell as well as eNPs to enter the cell via macropinocytosis as confirmed by confocal microscopy and flow cytometry studies using temperature-sensitive metabolic reduction, pharmacologic inhibitors, and fluid-phase marker co-localization. And, finally, we demonstrate, in vivo, the improved performance of paclitaxel when delivered using the eNPs compared to cremophor/ethanol, the current standard of care, in a mesothelioma model. I will conclude with results from a new project on using nanopores for detection of nucleic acids, of interest for cancer applications.