NanoClassifier · QCM for rapid label-free Bionano interface evaluation and screening of effectiveness of nano-targeting strategies for therapeutics

NanoClassifier - QCM for rapid label-free Bionano interface evaluation and screening of effectiveness of nano-targeting strategies for therapeutics.

Nanoscience constitutes a scientific frontier in which specialists can engineer materials on the length scale of a billionth of a meter. This capacity enables unprecedented developments in a wide array of applications including computer and mobile phone technologies, sustainable energy harvesting, and precision diagnostics and therapeutics. A number of therapeutic interventions at the nanoscale have been shown to hold considerable potential, however, challenges in efficacy and safety remain to date. Durable developments in nanomedicine and nanosafety rely on our understanding of interactions occurring at the interface between the nanoparticles and biological targets. It is now well-established that a “corona” of proteins and other biomolecules forms at such bio-nanointerface and is closely linked to the fate and behaviour of nanomaterials in vivo. At the heart of this bio-nanointerface lies the interactions between the nanoparticle corona and the receptors expressed on the cell membrane. Multiple competitive interactions occur in vivo, and in many cases non-specific binding blocks the targeting functionality of the nanoparticles, rendering them inactive. As such, the potential to improve the efficacy and safety of nanomedicines depends on our capacity to measure these interactions in a manner relevant to physiological conditions. In essence, this means to study interactions between nanoparticles and cells that express relevant receptors (e.g., liver cell receptors) in realistic biological environments (e.g., human plasma, in flow). Due to the absence of an in-depth understanding and a well-defined means to measure these receptor interactions in realistic biological environments, the existing nanoparticle strategies, which seem promising when tested under non-physiological conditions, have failed when tested in vivo. In turn, this has led to slow regulatory approval and adoption. NanoClassifier aimed to address a range of challenges currently hampering the implementation of nanotechnologies, both in medicine and generally in consumer products. This project was designed to develop a screening platform based on Attana Cell 200 for (a) characterization of the bio-nanointerface and identification of key molecular details for nanoparticle-cell interactions, and (b) tracking the interaction of nanoparticles with cells in a realistic biological environment. Together, NUID UCD and Attana AB have developed a cost-effective, high throughput screening platform for characterization of the bio-nanointerface and its cell-binding partners, providing the first high throughput label-free approach to the whole arena. We have established the core assets of the platform such as the nanoparticle and cell libraries for standardization and testing and made necessary adaptations of the instrument to allow for deployment in the nanotechnology arena. In addition, we worked to develop new platforms for the characterization of the protein corona at a sub-molecular level, with a focus on the exposure of epitopes of key biological interest. NanoClassifier, for the first time, offers a reproducible and widely usable means to fully characterize nanoparticle surface interactions in a biologically meaningful manner, filling a major gap in current scientific understanding and regulatory approval. We believe this will make low-cost screening and Phase 1 approvals of nanotherapeutics much more accessible. The methodologies developed in NanoClassifier also offer a major step toward generating a means of predicting the distribution and accumulation of nanoparticles in organs and tissues of interest. Since undesirable liver accumulation and consequent toxicity is a major roadblock to commercialization and exploitation, this would have a significant impact across the field. NanoClassifier Industry-Academia partnership has trained a number of Fellows in performing nanoparticle-based assays in a manner that facilitated knowledge transfer between the beneficiaries. Attana will use the knowledge accrued and joint publications in marketing and has included nanoparticle assays in their product offerings. Meanwhile, CBNI UCD will continue to develop the platform described and collaborate with Attana on future publications. The partnership will continue to participate and disseminate within conferences within the area and several of Attana’s customers are now performing nanoparticle-based screening. Project Website: http://www.nanoclassifier.eu/ Project Contacts: project-office@nanoclassifier.eu

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