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Polymer Synthesis for Life Improving (PoSyLife)

The research of the group is focused into the design, synthesis, characterization and validation of polymers for applications that impact the daily life of people, such as quality of artificial lighting, safe and sustainable packaging, and nanomedicine.

Staff: Prof. Roberto Simonutti, Dr. Michele Mauri

RESEARCH TOPICS

1) DESIGN OF SELF ASSEMBLING BLOCK COPOLYMERS NANOPARTICLES

Thanks to the rapid development of nanotechnology, polymer nanoparticles (NPs) have proved to be promising for the future of biomedical research. Of particular note is their use in drug  delivery as “smart carriers”. By virtue of their size in the nanometer scale, the NPs can cross very selective barriers such as the blood brain barrier and convey the drugs directly into the site of action, especially if it is enhanced with bioactive surface decoration. Strict requirements that guide biomedical applications of polymeric NPs include: monodispersity, low cytotoxicity, prolonged circulation time in the bloodstream, and biodegradability. A basic prerequisite to tackling this complex issue is the production of polymer nanoparticles with highly reproducible and controllable shape. Amphiphilic block copolymers (ABCs) are excellent candidates for the manufacture of NPs due to their ability to organize themselves spontaneously in nanostructures of different morphology, in the presence of a selective solvent such as water. Also, they can provide a good substrate for further decoration.

  1. Process Modeling: Polymeric nanosystems made from ABCs can present a wide range of morphologies varying from spherical to cylindrical micelles and vesicles (o  polymersomes). Due to the complexity of the delicate mechanisms that regulate the self-assembly of ABCs, there are numerous parameters, both chemical (total molecular weight, volume fraction of each block, interaction between the blocks) and methodological (NP fabrication process, choice of co-solvent, temperature, pH) that determine the final morphology of the NP ven considering the many examples in literature, it’s difficult to have a comprehensive and self-consistent picture of the self-assembly behaviour of polymers. One of our activities is the controlled synthesis of block copolymer with varying length and uncover the guiding principles that can impart them the desired shape.
  2. NPs for BBB crossing: using the principles described above, we specifically explore the range of shapes that can be obtained poly(ethylene oxide)-blockpoly( lactic acid) (PEO-b-PLA). This system is specifically suited for the application since PEO is highly hydrophilic, non-toxic, non-immunogenic and capable of preventing opsonization of NP allowing a high circulation time. PLA, used as a hydrophobic block, is characterized by low toxicity and high biodegradability. Both polymers are approved by the FDA and some pharmaceutical formulations have reached clinical trial. As such, we are working on it. We were able to reliably obtain a variety of promising shapes, including polymersomes and hierarchical superstructures, and we are working at their further functionalization. Also, we are planning a similar exploration of a new, promising class of biocompatible polymers: polyoxazolines.

2) DESIGN OF FUNCTIONALIZED NANOPARTICLES WITH INORGANIC CORE

The application of TiO2 nanostructures in nanobiotechnology and biomedicine has gained increasing attention during the past few years. In particular, highly curved crystalline nanoparticles (NPs) offer an enhanced reactivity for an easy conjugation with bioactive molecules, producing useful hybrid multifunctional nanodevices for simultaneous photodynamic therapy, drug delivery, and imaging. However, in a biological environment, without a proper stabilization, titanium dioxide NPs tend to aggregate and interact with the surrounding media, resulting to be cytotoxic and unfit for clinical treatments. Polymer grafting on the nanoparticle surface is an effective route to improve solubility, mobility, and tissue penetration and reduce toxicity and undesired interactions. Coating with polyethylene glycol (PEG) is particularly convenient because it is inexpensive, FDA-approved, prevents nanoparticles agglomeration, opsonization from he immune system, and therefore increases the in vivo circulation time.

  1. New approaches to grafting to Control over the grafting density is crucial for determining the polymer corona size and shape, which is directly connected to the system hydration and thus the dynamic behavior. Generally, a high grafting density is desirable to achieve complete coverage and improved biocompatibility. For this reason, PEG is commonly modified to increase its reactivity toward the nanoparticle surface. We explore the different relative reactivity of various polymer end groups within a “grafting to” functionalization scheme. The final density depends not only on the polymer surface interaction, but also on the cumulative interaction with grafted chains, modulated by their dynamics.
  2. Development of techniques for the surface studies A general part of our work is the development of a toolkit for quantitating the interactions of NPs, with the environment, both in view of applications (composite materials) and in predicting the bioactivity. In aqueous dispersions, the fast exchange of water with the surface allows using the extremely abundant 1H nuclei as probe of the surface energy. We study how the relaxivity of water dispersions of different titanium oxide NCs depends on their size and polymorphism. NMR can also be used to determine the nature of the ligand-crystal interaction by direct investigation of the decorated nanoparticles with Solid State NMR, provided that systems with sufficient coverage are available.

3) SCREENING OF MAGNETIC THERANOSTIC NANOPARTICLES

The tuning of magnetic properties is one of the most sought after features of nanoparticles. The capability of paramagnetic particles to accelerate the spin relaxation of nearby proton nuclei determines the potential applications as contrast agents for MRI. Besides this diagnostic application, it is also possible to use external fields to guide magnetic nanoparticles loaded with drugs to targets within the body, or even to combine both aspects into theranostic nanoparticles. The synthesis of such systems requires several optimization steps, since magnetic properties often depend on their size. Also, when layers of nanoparticles are grafted on their surface to help circulation in the body, or to host drug molecules, some magnetic properties can be again modified. Clinical MRI systems are certainly capable of monitoring the effect of each step and the quality of each batch, but MRI time is expensive and valuable for clinical investigations. Our group is equipped with a Minispec, the perfect solution for such relaxation studies, because it offers systems providing a magnetic field of 0.5 T, similar to some clinical MRI systems, and can be used to monitor the particle properties before going to murine or human experimentation.

SELECTED RECENT PUBLICATIONS:[1-12]
[1] D. Selli, M. Tawfilas, M. Mauri, R. Simonutti, and C. Di Valentin, “Optimizing PEGylation of TiO2 Nanocrystals through a Combined Experimental and Computational Study,” Chemistry of Materials, 2019/08/09 2019.
[2] D. Besghini, M. Mauri, and R. Simonutti, “Time Domain NMR in Polymer Science: From the Laboratory to the Industry,” Applied Sciences, vol. 9, p. 1801, 2019.
[3] C. Villa, M. Campione, B. Santiago-González, F. Alessandrini, S. Erratico, I. Zucca, et al., “Self-Assembled pH-Sensitive Fluoromagnetic Nanotubes as Archetype System for Multimodal Imaging of Brain Cancer,” Advanced Functional Materials, vol. 28, p. 1707582, 2018.
[4] M. Tawfilas, M. Mauri, L. De Trizio, R. Lorenzi, and R. Simonutti, “Surface Characterization of TiO2 Polymorphic Nanocrystals through 1H-TD-NMR,” Langmuir, vol. 34, pp. 9460-9469, 2018/08/14 2018.
[5] F. Meinardi, S. Ehrenberg, L. Dhamo, F. Carulli, M. Mauri, F. Bruni, et al., “Highly efficient luminescent solar concentrators based on earth-abundant indirect-bandgap silicon quantum dots,” Nat Photon, vol. 11, pp. 177-185, 03//print 2017.
[6] N. J. Brooks, F. Castiglione, C. Doherty, A. Dolan, A. J. Hill, P. A. Hunt, et al., “Linking the structures, free volumes, and properties of ionic liquid mixtures,” Chemical Science, vol. 8, pp. 6359-6374, 2017.
[7] E. Vismara, C. Bongio, A. Coletti, R. Edelman, A. Serafini, M. Mauri, et al., “Albumin and Hyaluronic Acid-Coated Superparamagnetic Iron Oxide Nanoparticles Loaded with Paclitaxel for Biomedical Applications,” Molecules, vol. 22, p. 1030, 2017.
[8] L. M. Polgar, E. Hagting, P. Raffa, M. Mauri, R. Simonutti, F. Picchioni, et al., “Effect of Rubber Polarity on Cluster Formation in Rubbers Cross-Linked with Diels–Alder Chemistry,” Macromolecules, vol. 50, pp. 8955-8964, 2017/11/28 2017.
[9] A. Monguzzi, A. Oertel, D. Braga, A. Riedinger, D. K. Kim, P. N. Knüsel, et al., “Photocatalytic Water- Splitting Enhancement by Sub-Bandgap Photon Harvesting,” ACS Applied Materials & Interfaces, vol. 9, pp. 40180-40186, 2017/11/22 2017.
[10] M. Gregori, D. Bertani, E. Cazzaniga, A. Orlando, M. Mauri, A. Bianchi, et al., “Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood–Brain Barrier In Vitro,” Macromolecular Bioscience, vol. 15, pp. 1687-1697, 2015.
[11] A. Raspa, A. Marchini, R. Pugliese, M. Mauri, M. Maleki, R. Vasita, et al., “A biocompatibility study of new nanofibrous scaffolds for nervous system regeneration,” Nanoscale, vol. 8, pp. 253-65, Dec 17 2015.
[12] M. e. a. Mauri, “BIOCOMPATIBLE NANOVECTORS FROM SELF-ASSEMBLED AMPHIPHILIC BLOCK COPOLYMERS FOR BRAIN MEDICINE APPLICATIONS,” AIM 2014 Conference, 2014.