NIPAm-Based Modification of Poly(L-lysine): A PH-Dependent LCST-Type Thermo-Responsive Biodegradable Polymer

Overview

Journal Polymers (Basel)

Publisher MDPI

Date 2022 Feb 26

PMID 35215715

Authors

Aggeliki Stamou

Hermis Iatrou

Constantinos Tsitsilianis

Affiliations

Soon will be listed here.

Abstract

Polylysine is a biocompatible, biodegradable, water soluble polypeptide. Thanks to the pendant primary amines it bears, it is susceptible to modification reactions. In this work Poly(L-lysine) (PLL) was partially modified via the effortless free-catalysed aza-Michael addition reaction at room temperature by grafting N-isopropylacrylamide (NIPAm) moieties onto the amines. The resulting PLL-g-NIPAm exhibited LCST-type thermosensitivity. The LCST can be tuned by the NIPAm content incorporated in the macromolecules. Importantly, depending on the NIPAm content, LCST is highly dependent on pH and ionic strength due to ionization capability of the remaining free lysine residues. PLL-g-NIPAm constitutes a novel biodegradable LCST polymer that could be used as "smart" block in block copolymers and/or terpolymers, of any macromolecular architecture, to design pH/Temperature-responsive self-assemblies (nanocarriers and/or networks) for potential bio-applications.

Citing Articles

Multi-stimuli-responsive Hydrogels for Therapeutic Systems: An Overview on Emerging Materials, Devices, and Drugs.

Garshasbi H, Soleymani S, Naghib S, Mozafari M Curr Pharm Des. 2024; 30(26):2027-2046.

PMID: 38877860 DOI: 10.2174/0113816128304924240527113111.

Amphiphilic Polyethylene--poly(L-lysine) Block Copolymer: Synthesis, Self-Assembly, and Responsivity.

Pei L, Ma H, Jiang Y, Zheng H, Gao H Int J Mol Sci. 2023; 24(6).

PMID: 36982576 PMC: 10052655. DOI: 10.3390/ijms24065495.

pH-Responsive, Thermo-Resistant Poly(Acrylic Acid)-g-Poly(boc-L-Lysine) Hydrogel with Shear-Induced Injectability.

Karga M, Kargaki M, Iatrou H, Tsitsilianis C Gels. 2022; 8(12).

PMID: 36547341 PMC: 9778197. DOI: 10.3390/gels8120817.

Advances in Biodegradable Soft Robots.

Kim J, Park H, Yoon C Polymers (Basel). 2022; 14(21).

PMID: 36365570 PMC: 9658808. DOI: 10.3390/polym14214574.

A Multiple-Stimuli-Responsive Amphiphilic Copolymer for Antifouling and Antibacterial Functionality via a "Resistance-Kill-Release" Mechanism.

Liao X, Niu K, Liu F, Zhang Y Molecules. 2022; 27(16).

PMID: 36014312 PMC: 9416764. DOI: 10.3390/molecules27165059.

References

Lanzalaco S, Armelin E . Poly(N-isopropylacrylamide) and Copolymers: A Review on Recent Progresses in Biomedical Applications. Gels. 2019; 3(4). PMC: 6318659. DOI: 10.3390/gels3040036. View

Popescu M, Liontos G, Avgeropoulos A, Tsitsilianis C . Stimuli responsive fibrous hydrogels from hierarchical self-assembly of a triblock copolypeptide. Soft Matter. 2014; 11(2):331-42. DOI: 10.1039/c4sm02092h. View

Bosica G, Abdilla R . Aza-Michael Mono-addition Using Acidic Alumina under Solventless Conditions. Molecules. 2016; 21(6). PMC: 6273892. DOI: 10.3390/molecules21060815. View

Campbell J, Vikulina A . Layer-By-Layer Assemblies of Biopolymers: Build-Up, Mechanical Stability and Molecular Dynamics. Polymers (Basel). 2020; 12(9). PMC: 7564420. DOI: 10.3390/polym12091949. View

Halperin A, Kroger M, Winnik F . Poly(N-isopropylacrylamide) Phase Diagrams: Fifty Years of Research. Angew Chem Int Ed Engl. 2015; 54(51):15342-67. DOI: 10.1002/anie.201506663. View

Chopko C, Lowden E, Engler A, Griffith L, Hammond P . Dual responsiveness of a tunable thermo-sensitive polypeptide. ACS Macro Lett. 2014; 1(6):727-731. PMC: 4036704. DOI: 10.1021/mz300088w. View

Iatrou H, Frielinghaus H, Hanski S, Ferderigos N, Ruokolainen J, Ikkala O . Architecturally induced multiresponsive vesicles from well-defined polypeptides: formation of gene vehicles. Biomacromolecules. 2007; 8(7):2173-81. DOI: 10.1021/bm070360f. View

Grigsby J, Blanch H, Prausnitz J . Effect of secondary structure on the potential of mean force for poly-L-lysine in the alpha-helix and beta-sheet conformations. Biophys Chem. 2002; 99(2):107-16. DOI: 10.1016/s0301-4622(02)00138-2. View

Shen Y, Fu X, Fu W, Li Z . Biodegradable stimuli-responsive polypeptide materials prepared by ring opening polymerization. Chem Soc Rev. 2014; 44(3):612-22. DOI: 10.1039/c4cs00271g. View

10.

Xiao Y, Tang C, Chen Y, Lang M . Dual stimuli-responsive polypeptide prepared by thiol-ene click reaction of poly(l-cysteine) and N, N-dimethylaminoethyl acrylate. Biopolymers. 2019; 110(9):e23318. DOI: 10.1002/bip.23318. View

11.

Dzwolak W, Muraki T, Kato M, Taniguchi Y . Chain-length dependence of alpha-helix to beta-sheet transition in polylysine: model of protein aggregation studied by temperature-tuned FTIR spectroscopy. Biopolymers. 2004; 73(4):463-9. DOI: 10.1002/bip.10582. View

12.

Zhang Y, Furyk S, Bergbreiter D, Cremer P . Specific ion effects on the water solubility of macromolecules: PNIPAM and the Hofmeister series. J Am Chem Soc. 2005; 127(41):14505-10. DOI: 10.1021/ja0546424. View

13.

Zheng M, Pan M, Zhang W, Lin H, Wu S, Lu C . Poly(α-l-lysine)-based nanomaterials for versatile biomedical applications: Current advances and perspectives. Bioact Mater. 2020; 6(7):1878-1909. PMC: 7744653. DOI: 10.1016/j.bioactmat.2020.12.001. View

14.

Chen C, Wang Z, Li Z . Thermoresponsive polypeptides from pegylated poly-L-glutamates. Biomacromolecules. 2011; 12(8):2859-63. DOI: 10.1021/bm200849m. View

15.

Stuart M, Huck W, Genzer J, Muller M, Ober C, Stamm M . Emerging applications of stimuli-responsive polymer materials. Nat Mater. 2010; 9(2):101-13. DOI: 10.1038/nmat2614. View

16.

Klouda L . Thermoresponsive hydrogels in biomedical applications: A seven-year update. Eur J Pharm Biopharm. 2015; 97(Pt B):338-49. DOI: 10.1016/j.ejpb.2015.05.017. View