The aim of this proposal is the development and optimisation of virus-like nanoparticles (NPs) to be used as a targeted drug delivery vessel that non-toxically penetrates cell walls and delivery drugs for diseases such as cancer. The NPs are composed of a metallic core and an organic coating with chemically linked drug molecules that can be released once inside the cell.
Background
Viruses are the most sophisticated and efficient drug delivery carriers that we know: they can deliver large amounts of genetic material to targeted cells, subjecting cell functions to their needs. In many aspects, modern medicine aims to do the same thing, e.g. to introduce new genetic materials into cancer cells so as to alter their fate. In addition, it is necessary for such delivery to bypass the immune response of the targeted organism.
Aim
Here we aim to develop and optimise synthetic analogues to viruses able to safely and efficiently deliver drugs/genetic material to targeted cells while minimising the triggered immune response and any toxic side-effect. We will use metallic NPs coated with a carefully selected mixture of organic molecules. Previous work has demonstrated that a mixture of dissimilar organic molecules bound to the NP metallic core can spontaneously form molecule-wide domains (stripes) at the surface of the NP yielding so-called ‘striped NP’. Striped NPs present unusual properties: they can spontaneously and directly cross the cell wall as some viruses do, carrying with them a molecular cargo. This ability is very attractive for drug delivery because no dynamical cellular uptake is needed and cell damage is minimised. We intend to synthesise, test and optimise different lines of NPs and establish a library of safe, efficient drug delivery carriers. In particular, we will 1. Study the effects of the NPs synthesis’ parameters on the NPs’ penetration ability, 2. Optimise the functionalisation of the NPs with genetic material and study the effects of the cargo on cell-penetration, 3. Create virus-like assembly using ‘striped NPs’ and synthetic lipids. The work will be done in collaboration with the MIT (Cambridge, USA) for in-vivo delivery and with the IIT (Lecce, Italy) for all of toxicity studies. Modelling will be done by collaborators at the University of Michigan (Ann Arbor).
Significance
This project’s significance in nanomedicine lies in the creation of very efficient drug delivery tools with minimal to no side-effects (e.g. cyto-toxicity), which is very important with regard to cancer therapy, in particular. Other more fundamental aspects, such as understanding the key parameters enabling NPs’ cell penetration and synthesis of virus-like structures, should also greatly contribute to the creation of a rational base and a theoretical framework for the future design of bio-compatible nano-objects able to reach designated regions of a living organism with a cargo.
Original title: Novel NPs for Efficient and Safe Drug Delivery
Grant: CHF 300’000.-
Duration: 36 months
Project leader
- Prof. Francesco Stellacci