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Super resolution imaging of nanoPMOs for cancer drug delivery

Project description

Optimising drug delivery nanocarriers for clinical use

Recent years have witnessed an expansion of nanotechnology-based drug delivery carriers. However, lack of information on the various structural and biological features of these nanocarriers has limited their therapeutic applications. To address this, the EU-funded MANTARGET project is optimising the physicochemical properties such as size, shape and surface chemistry of biodegradable nanocarriers suitable for clinical applications. The idea is to develop nanocarriers capable of targeting mannose-6-phosphate receptors, which are over-expressed in prostate cancer, and determine their cell specificity, interaction and degradation following intracellular internalisation, through super-resolution microscopy (STORM). Moreover, studying the toxicity of these nanocarriers is significant prior to their clinical application in delivering chemotherapeutic drugs to cancer cells.

Objective

In recent years, nanomaterial-based various drug delivery carriers have been developed for the potential targeted cancer therapy. However, still the advanced study for optimization of size, shape, surface chemistry of the nanocarrier and observation of biological interaction and evaluation of such nanocarrier are not well-developed that limit their use for the efficient clinical applications. Therefore, superior understandings of the cellular interaction of the nanocarrier with different physicochemical properties are essential and challenging for improved the cancer treatments. In this project, we will focus on the optimization of different physicochemical properties of nanocarrier such as size, shape, surface chemistry and etc via investigation of its biological interaction and evaluation by a potent imaging technique. For this purpose, we will synthesize a library of efficient biodegradable drug delivery carrier periodic mesoporous organosilica nanoparticles (nanoPMOs) with
controlled size and shape and then functionalized with different targeting ligands with the controlled number per nanoparticle for mannose-6-phosphate receptor over-expressed prostate cancer. Then we will study the nanoPMOs-prostate cancer cell interactions, internalization pathway and intracellular degradation of nanoPMOs through the stochastic optical reconstruction microscopy (STORM). We will further evaluate the drug delivery efficacy of nanoPMOs and toxicity mechanism of drug loaded nanoPMOs to support microscopic observation. Thus the result of this biological interaction and evaluation of nanoPMOs with different physicochemical properties via super-resolution microscope STORM will help to develop a novel drug delivery carrier for prostate cancer therapy with optimal properties for clinical applications.

Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 184 707,84
Address
RUE MICHEL ANGE 3
75794 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 184 707,84