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Nanomaterials to help complex drugs overcoming biological barriers

Fortunately, the continuously improved understanding of the biological barriers and the molecular biology associated to pathological conditions is paving the way for a more comprehensive and rational design of formulations of these complex drugs based on the use of nanotechnology. Our laboratory, with decades of experience in the formulation of macromolecules using polymer nanoparticles, has significantly contributed to this field. As an example, in the 90’s we were the first to report that nanoparticles made of either PLA-PEG or chitosan were efficient vehicles for the transmucosal delivery of proteins antigens and polynucleotides. The result of our subsequent efforts is an array of nanotechnologies that can be used to deliver proteins across mucosal surfaces, and, also, to facilitate their intracellular delivery following parenteral administration.

In my presentation, I will focus on the design of protein and RNA carriers that could be used in different therapeutic areas: (i) oral delivery of peptides intended to treat either local or systemic diseases, (ii) nanovaccines designed to prevent diseases, i.e. HIV as well as to treat diseases, i.e. diabetes and multiple sclerosis, (iii) nose-to-brain delivery of RNA for the treatment of Alzhimer disease, and (iv) delivery of mAb targeted to intracellular onco-proteins, as new oncological treatments.

Overall, our experience in this field has benefited from integrative approaches adopted by specifically designed consortia. Hopefully, the results of these cooperative efforts will help to accelerate the progress of a rational design of protein-based nanomedicines.

The MACS technology enables the magnetic separation of cell populations based on surface antigens. It is a fast and gentle method for the isolation of viable and functional cells in high purities and recoveries by labeling cell epitopes with specific antibodies that have been conjugated to superparamagnetic nanoparticles. The highly efficient isolation of targeted cells is facilitated by utilizing high-gradient magnetic columns in the cell separation step. This ingenious technological combination supports complete workflows and accesses virtually any cell type of interest. It has been used in thousands of manual and automated high-throughput settings to date, starting from a broad range of cell sources, such as whole blood and blood products, as well as tissues from various species. The talk will illustrate the continuous development of the MACS technology and focuses on some more recent innovative solutions utilized in basic and translational cell research, as well as clinical cell therapy applications that have been made available to the scientific community within the last 30 years.

Thermal therapies with magnetic and plasmonic nanoparticles and long-term fate in the intracellular environment

Nanoparticles-based thermal therapy has emerged to propose alternative treatment and decrease side effects. We recently compared the heating potential of magnetic nanoparticles under magnetic hyperthermia or photothermia [1,2], of plasmonic nanoparticles under photothermia [3], or the combination of both [4-8], towards synergistic solutions to complete cancer cell destruction. The therapeutic use of nanoparticles then still raises the more general issue of intracellular nanoparticle long-term fate. We have developed cell spheroids models and magneto-thermal tools to monitor their intracellular integrity. It evidenced a massive intracellular degradation [9,10], which could be prevented by a polymeric coating [11] or an inert gold shell [12,13]. Remarkably, human cells could also biosynthesize their own magnetic nanoparticles, from the intracellular degradation products of synthetic ones [14].
[1] Advanced Functional Materials, 28, 1803660 (2018); [2] Journal of Controlled Release, 279, 271-281 (2018); [3] Advanced HealthCare Materials, 5, 1040- 48 (2016); [4] ACS Nano, 9, 2904-2916 (2015); [5] ACS nano 2016, 10, 2436-2446 (2016); [6] Nanoscale, 7, 18872-18877 (2015); [7] Theranostics, 9, 1288 (2019); [8] Theranostics, 9, 5924 (2019); [9] ACS nano, 10, 7627-7638 (2016); [10] Nature Communications, 8, 400 (2017); [11] Nanoscale, 11, 16488 (2019); [12] Advanced Functional Materials, 27, 1605997 (2017); [13] ACS nano, 12, 6523-6535 (2018); [14] PNAS 116, 4044-4053 (2019);

The Route to Complex Medicines from Science to Regulation

We discuss the microscopic molecular principles of organization at the nanoscale that may be used to control and direct biological processes. Increasing understanding is emerging about the detailed consequences of molecular organizations on the surface of nanostructures and the role this has at cellular and organ (e.g. liver clearance) immune and others. However, now the first detailed information is also becoming available for the role of nanoscale shape, and the potential role of shape in stimulating living systems.
The talk will stress the potential for a structured and rational design approach, based on fundamental understanding to improve on current phenomenological design approaches alone. Some considerations of scaling up, in GLP-like conditions are given, and the potential for these combined approaches to lead to realistic therapies. We stress the potential to build a durable science, with great potential impact, for the long term.