Project: Synthesis of Novel Cyclic Polycations for Enhanced Gene Delivery and Antimicrobial Therapies
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The ever-increasing threats of antibiotic resistance and the expanding needs for improved gene therapy techniques have urged researchers to explore new routes in polymer chemistry. This project aims to design and synthesize a series of novel cyclic polycations based on positively charged poly(2-oxazoline)s or polyethylene imine [1,2]. It is hypothesized that these innovative polymers, characterized by unique cyclic architectures and charge densities, can effectively perform in gene delivery applications and antimicrobial roles, potentially surpassing their linear chain counterparts.
Several synthetic strategies (such as cationic ring-opening polymerizations and subsequent post-polymerization modifications) will be utilized to yield cyclic polycations of different structures and cycle sizes, ensuring high cyclization yields. The synthesis will be designed to produce polymers of different charge densities and distributions, thereby allowing the study of structure-activity relationships. Both physical and chemical characteristics of the synthesized cyclic polymers will be analyzed. Methods like nuclear magnetic resonance spectroscopy (NMR), size-exclusion chromatography (GPC), matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy, and dynamic light scattering (DLS) will be employed for the characterization. The solution properties of these polymers will be compared to their linear analogs to identify the benefits of cyclic architecture.
Selected cyclic polycations will be assessed for their antimicrobial properties against antibiotic-resistant bacteria (e.g., S. Aureus). The effectiveness of these new structures will be compared to the linear analogs, potentially illuminating new pathways in the fight against antibiotic resistance. Furthermore, the cyclic polycations will be utilized to form polyplexes with nucleic acids. The resulting polyplexes will be studied for their potential in transfection, a key process in gene therapy. The efficacy of these new cyclic polymers for gene delivery will be compared to linear counterparts to evaluate their potential advantages.
This comprehensive project holds significant potential to advance our understanding of cyclic polycations, offering a unique perspective on their potential as effective antimicrobial agents and gene delivery systems. Ultimately, our findings may provide new avenues for the development of advanced materials in health sciences.
References:
[1] Zhou, Min, et al. Angew. Chem. Int. Ed. 59.16 (2020): 6412-6419.
[2] Cortez, Mallory A., et al. J. Am. Chem. Soc. 137.20 (2015): 6541-6549.
Salary: co-founding 1000 EUR/month is ensured
Co-founding resources: Group of Polymer synthesis and Biomaterials, Department of Physical and Macromolecular Chemistry
Department: Department of Physical and Macromolecular Chemistry, faculty of Science
upervisor: Ondřej Sedláček, Ph.D.
E-mail: sedlacek@natur.cuni.cz
Phone: +420 221 951 311
Position available from: January 1, 2024
Deadline date for applications: July 25, 2023
Applicants must submit required documents to: sedlacek@natur.cuni.cz (project supervisor) and in a copy to pavla.pouskova@natur.cuni.cz (International Department)
Deadline is closed
