SUMMARY

The goal of this proposal is to develop a technological foundation to synthesize and evaluate cancer therapeutic polymer-based nanomedicines using microfluidic platform and to optimize, and characterize it for the controlled drug release within tumor environment. The project will be done in three phases; In phase I, the main goal would be evaluating the ability of on-chip nanoparticle (NP) formation on controlling the physical properties of prepared NPs. Size, polydispersity, morphology, and surface charge of NPs will be characterized in this phase. In phase II, we will focus on development of complex NPs to address the requirements of next-generation nanomedicine. The main goal will be synthesis of hybrid (organic-inorganic and organic-organic) NPs, multilayer NPs as well as ligand-coated NPs. For hybrid NPs, encapsulation of gold and magnetic NPs inside polymeric particles will be examined for the theranostic applications. In the case of multilayer NPs the main goal is to protect NPs from in vivo degradation (e.g. in oral delivery) as well as on-target unmasking of the coated NPs. We will also try to make electrostatic ligand-coated NPs for active targeting of cancerous cells. Full sets of mentioned evaluations will be done to characterize the developed complex NPs as well. In phase III, we will mainly focus on the biological behavior of microfluidic-directed synthezied NPs. In vitro release profile of drug-loaded NPs will be evaluated. Using two-dimensional cultures of cancer cell lines and subsequently cellular spheroids, NPs-cell interactions, cellular toxicity, and cellular uptake of NPs will be assessed. Tumor-on-chip model will be tried as a real-time analytical method to evaluate the NP accumulation at simulated physiological flow condition. The specific goal of this phase is to design a miniaturized tumor microenvironment on a chip using microfluidics technique to recapitulate the key parameters acting in vivo including 3D tumor environment, cancer cell aggregates, physiological scaling and flow rates. Such results will be achieved through the possibility for optical window to real-time evaluation and sampling from the designed chambers on the microfluidic platforms. Overall we expect that this research will provide us with broad information on how NP design can affect and control the efficacy of cancer therapeutic nanomedicine.