CANCER NANOMEDICINE

Optimizing the Delivery of Nanomedicine to Solid Tumors

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 Obiettivo del progetto (Objective)

'Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. While the enhanced permeability and retention effect has served as a key rationale for using nanoparticles to treat solid tumors, it does not enable uniform delivery of these particles to all regions of tumors in sufficient quantities. This heterogeneous distribution of therapeutics is a result of physiological barriers presented by the abnormal tumor vasculature and interstitial matrix. These barriers are in large part responsible for the modest survival benefit offered in many cases by clinically approved nanotherapeutics and must be overcome to realize the promise of nanomedicine in patients. More specifically, we need to determine the design criteria - the size, charge and configuration of various nanoparticle platforms - that optimize drug delivery to tumors. Here, I propose the development of a mathematical framework for the delivery of therapeutic nanoparticles to solid tumors. The model will account directly for the properties of the tumor micro-environment as well as for the properties (size, charge and configuration) of nanoparticles to predict their intratumoral distribution. I will specify the model to a human sarcoma and a human mammary carcinoma cell line for which a complete set of experimental data that characterize their micro-environment exists. Informed by these experimental measurements, I will use the mathematical model to construct 'design maps' that will predict the nanoparticle properties that optimize intratumoral delivery, and thus the efficacy of cancer therapy. I will also employ the model to investigate if modifications in the tumor micro-environment with the use of anti-angiogenic and anti-fibrotic agents can improve the distribution of nanomedicine to solid tumors.'

Introduzione (Teaser)

Short drug circulation times and difficulty targeting tumours are two of the challenges associated with existing cancer treatments. To improve treatment efficacy, scientists worked on utilising nanomedicine in the fight against cancer.

Descrizione progetto (Article)

Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. The enhanced permeability and retention (EPR) effect has served as a key rationale for using nanoparticles to treat solid tumours. However, issues with uniform delivery of nanoparticles to all regions of a tumour in sufficient quantities needs to be dealt with.

The goal of the EU-funded 'Optimizing the delivery of nanomedicine to solid tumours' (http://www.eng.ucy.ac.cy/cancernano/ (CANCER NANOMEDICINE)) project is to develop mathematical models for the delivery of therapeutic nanoparticles to solid tumours. The model has to predict their intra-tumoural distribution based on the tumour microenvironment and the properties of nanoparticles.

During the first two years of the project, researchers developed software to predict the transport of therapeutic agents' through blood into the tumour. The model accounted for key factors including tumour vascular network of any geometry and openings of the tumour vessel wall that defines the EPR effect. This model was tested on two types of murine breast tumours and used to predict what particle size and charge optimises delivery of nanoparticles.

Project findings were published in high-impact journals, revealing that nanoparticles with diameters below 20 nanometres can be more effectively administered to solid tumours. The positively-charged nanoparticles have superior trans-vascular flow to tumours compared to their negatively-charged or neutral counterparts. Normalisation of tumour blood vessels improves the delivery of only small-size nanoparticles.

The project results could provide valuable guidelines for treatment of solid tumours through nanomedicine. Developed models decipher use of vascular normalisation to modify the tumour microenvironment and improve the distribution of nanoparticles.