Optimizing nanomaterial delivery to solid tumors by pharmaceutical and physical means.

The main aim of the current project lies in the development of novel methods to improve the delivery of nanomaterials (NMs) to solid tumors, paving the way for a more specific delivery of anti-cancer therapeutics, minimizing any unwanted side-effects and reducing costs of therapy. To reach these goals, a highly multidisciplinary project is set up, using different sizes of gold NMs, as a role model for NM types, owing to its high biomedical relevance and precise control over physicochemical properties. These NMs will be tested in different animal models, where delivery efficacy will be increased through personalized classification of vascular properties, the use of alternative mechanisms to enhance NM uptake by cancer cells and the use of vascular remodeling agents.

In order to achieve the overall aim, the following objectives have been put forward:

- Validate the ability of different NM sizes to reach the tumor at different levels.

- Develop, optimize and validate a simple, high-throughput method to evaluate blood flow and vascular leakiness in solid, surface-located tumors using optical imaging.

- Validate the ability of iRGD therapy to affect NM tumor uptake and evaluate differences in NM delivery efficacy and intracellular localization.

- Validate the ability to use 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one) (3-PO) as a vascular remodeling agent to boost NM delivery to the tumor.