Applications of nanosystems are relevant in different items spanning from material science to biomedicine. Remind, however, that their biocompatibility is still an open question. Preparing bioinspired nanoparticles (NPs) with manifold functionalities requires the optimization of their structure, size, shape, surface area, chemical composition, solubility and local geometry, Combination of all such properties ensures perspectives in biomedicine, despite possible toxicity is to be considered.
Hybrids can be functionalized and properly designed by combining covalent and/or non covalent functionalization processes. Therefore, the design of multi-functional hybrids NPs may improve the efficacy of existing formulations and reduce current drawbacks, such as compatibility with different environments. We adopt a bottom-up approach to obtain hybrids having performances and properties not occurring in the single components. Size, morphology, functionalities, and other physico-chemical features of NPs will be tuned to achieve materials responsive to stimuli such as temperature, pH or ionic strength. The proposal will focus on fluid or semifluid matrices such as:
1. Biopolymer-coated cat-anionic vesicles
2. nucleic acid-wrapped carbon nanotubes (CNTs) and their dispersion in vesicular medium
3. temperature- and pH-sensitive peptide-polymer conjugates
4. temperature- and pH-sensitive lipopeptides
5. temperature- and pH-sensitive cholic acid derivative-polymer conjugates
6. pH-sensitive cholic acid derivative-peptide conjugates with antimicrobial activity
SAXS, DLS, AFM, electron microscopies (SEM, TEM and cryo-TEM), NMR, circular dichroism, fluorescence, rheology, electropho-retic mobility, and relaxation methods will be jointly used to investigate and optimize size, shape, charge and mechanical proper-ties of NPs. Finally, the toxicity and the interaction between self-assemblies and cells will be assessed by flow cytometry analysis on the most promising NPs.
The innovation of our proposal mainly deals with the synthesis and the characterization of nanosystems which will be performed by many different approaches. In fact, reasons for joining together so much diverse expertise are dictated by the complexity of the systems. To this end, different expertise, including those related to colloidal systems, peptide synthesis and structural characterization, preparation of self-assembling polymers obtained with controlled radical polymerizations, will be properly combined to characterize NPs with unprecedented level of details with different approaches and techniques.
We plan to prepare NPs and elucidate their structure and morphology by different physico-chemical and advanced microscopy methods. This procedure will avoid undesired effects, such as phase separation, and should increase the biocompatibility of NPs. Surface-functionalization will be carried out by appropriate strategies.
For instance, CNTs may be wrapped by polysaccharides, proteins, DNA, RNA, and synthetic polymers which can be pH or thermo- sensitive. Block copolymers of the PEO-PPO-PEO family could be relevant on this regard. Similar considerations apply to the other systems described in this proposal, namely to lipopeptides and peptide-polymer conjugates with pH and temperature dependent associating moieties. We will use mechanisms-based high-throughput screenings to forecast the expected properties of NPs.
Thanks to the combination of different expertise, the present research project is surely innovative, and could substantially contribute to the development of advanced technologies based on different NPs. The successful application of such technologies may also lead to breakthroughs in materials design and in the development of new nano-based products. The combination of the different research experience and skills of the partners will pave the way towards these ambitious goals.