Remotely actuated re-shaped nanocarriers for tumour targeting

Project Information

HybridNP

Grant agreement ID: 101061967

DOI

10.3030/101061967

Project closed

EC signature date 10 March 2022

Start date 1 April 2022

End date 30 September 2023

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

THE HEBREW UNIVERSITY OF JERUSALEM
Israel

Periodic Reporting for period 1 - HybridNP (Remotely actuated re-shaped nanocarriers for tumour targeting)

Reporting period: 2022-04-01 to 2023-09-30

Summary of the context and overall objectives of the project

In the ongoing ERC MTrix project, my team have demonstrated that the mechano-physical properties of nanoparticles (NPs), such as size, shape, and elasticity, play a crucial role in their interaction with cancer cells. These findings suggest that by carefully controlling these parameters during the fabrication process, inert nano and micro carriers can be designed to preferentially target specific cells, including aggressive cancer cells, without the need for affinity ligands. This concept, known as "Mechanical targeting," holds promise for applications in therapy, diagnostics, and imaging. While NPs show great potential in cancer drug therapy, the delivery of a single therapeutic agent may not be sufficient to eradicate tumors. The use of multifunctional NPs containing metals is proposed as a promising technology that combines physical actuation with pharmacological activity. Examples include magnetic guidance, tissue hyperthermia in response to irradiation, and plasmonic effects. Integrating multiple therapeutic mechanisms in cancer therapy can potentially enhance treatment outcomes by minimizing drug resistance and prolonging efficacy. Despite the development of many protocols for producing multifunctional polymer/metal hybrid NPs, only a few are compatible for drug delivery, and none are suitable for producing asymmetric NPs. The lack of methods for producing anisotropic NPs represents a significant gap in technology, especially considering the importance of NP shape in tumor specificity. This project aimed to produce shape-controlled metal/polymer nanoparticles that can open new possibilities for enhancing the effectiveness of cancer treatments.
We have met the project milestones successfully and introduced a groundbreaking technology for reshaping nanoparticles remotely, based on thermoresponsive materials. A provisional patent application covering both the materials and methods for mechanically targeting cells was filed. Currently, our focus is on refining the protocol and developing a scalable production process. The main results are now being summarized for manuscript to describe our methodology, and my team already published two relevant papers on different aspects of our work in the past few months.
The impact of our project is beyond the scientific community and is expected to lead to a novel therapeutic approach in precision drug delivery that may provide a mean for better and safer cancer therapies.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Two main achievements were successfully achieved. The first is to develop a robust technology that enables the deposit of various metals (copper, gold and iron) on solid polymeric nanoparticle templates. This aspect is critical as the metal part add additional function to drug carrier and leverage synergic activity between hyper thermic reaction and drug action.
The second main achievement is related to the ability to create anisotropic nanoparticles with controllable elongation. While the original plan was to stretch PCL particle with sheer and magnetic force, we found that this is not feasible since the metal cap is disconnecting from the polymer, therefore we use our contingency plan and developed a stretching protocol in which PCL nanoparticles were stretched in films to desired degrees and were decorated with iron post solidification.
Experimentally we showed the formulation of compound-loaded PCL nanoparticles. We showed the ability to form elongated shapes of various degrees, we demonstrated the mechanical selectivity of the elongated particles to internalized into more aggressive melanoma cells. Moreover, the formation of thin iron patch were shown on the elongated template particles and the heat under NIR laser

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project is highly impactful for the drug delivery field. We introduce a novel technology which can be used to functionalize solid nanoparticles (with any drug) with metals to add additional function. Specifically, we showed an innovative concept that thermosensitive polymer can respond to melt down a carrier in response to NIR – this control the timing and localization of drug action. Specifically, we expended this concept to include particles with diverse shapes that showed mechanical selectivity towards more aggressive cancer cells. Importantly we filed a provisional patent application specifically around the ability to reshape metal/polymer nanoparticles remotely. In the next stage we may integrate our metal/polymer nanoparticles with a tumor-on-a-chip system to explore a path for personalized drug delivery to cancer patients based on mechanical tuning of drug carriers.