Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers

Hui Liu; Xiao Liu; Yuan-Qiao Cao; Ming Liu; Miao-Miao Han; Sheng-Xiang Ji

doi:10.1007/s10118-022-2859-1

Your Location：

Home >

Browse articles >

Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers

RESEARCH ARTICLE | Updated：2023-01-18

- Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers
- Chinese Journal of Polymer Science Vol. 41, Issue 3, Pages: 345-355(2023)
- Affiliations：
  
  a.Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
  b.University of Science and Technology of China, Hefei 230026, China
- Author bio：
  
  hanmiaomiao@ciac.ac.cn (M.M.H.)
  sji@ciac.ac.cn (S.X.J.)
- Funds：
- DOI：10.1007/s10118-022-2859-1
  CLC：
- Received：18 July 2022，
  
  Revised：2022-8-18，
  
  Accepted：23 August 2022，
  
  Online First：20 October 2022，
  
  Published：01 March 2023
- Accepted：
Scan QR Code
Liu, H.; Liu, X.; Cao, Y. Q.; Liu, M.; Han, M. M.; Ji, S. X. Engineering antibacterial activities and biocompatibility of hyperbranched lysine-based random copolymers. Chinese J. Polym. Sci. 2023, 41, 345–355

Hui Liu, Xiao Liu, Yuan-Qiao Cao, et al. Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers[J]. Chinese Journal of Polymer Science, 2023, 41(3): 345-355.
Liu, H.; Liu, X.; Cao, Y. Q.; Liu, M.; Han, M. M.; Ji, S. X. Engineering antibacterial activities and biocompatibility of hyperbranched lysine-based random copolymers. Chinese J. Polym. Sci. 2023, 41, 345–355 DOI： 10.1007/s10118-022-2859-1.

Hui Liu, Xiao Liu, Yuan-Qiao Cao, et al. Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers[J]. Chinese Journal of Polymer Science, 2023, 41(3): 345-355. DOI： 10.1007/s10118-022-2859-1.

摘要

The toxicity of hyperbranched poly(lysine) (HPL) was engineered by copolymerizing lysine with hydrophobic amino acids such as alanine

tryptophan

or phenylalanine to obtain hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered.

Abstract

Antimicrobial peptides (AMPs) have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance. Hyperbranched polylysine (HPL)

an AMP mimics

has gained attention due to its broad-spectrum antibacterial activities

but it also suffers from high toxicity. Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine (K) with a hydrophobic amino acid

e.g.

alanine (A)

tryptophan (W) or phenylalanine (F)

to afford hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and

in vivo

toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized. The

G. mellonella

infection model demonstrates that the copolymers are effective against the

S. aureus

infection

in vivo

. The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers.

关键词

Keywords

references

Hutchings, M. I.; Truman, A. W.; Wilkinson, B . Antibiotics: past, present and future . Curr. Opin. Microbiol. , 2019 . 51 72 - 80 . DOI: 10.1016/j.mib.2019.10.008 http://doi.org/10.1016/j.mib.2019.10.008 .

Broughton, C. E.; Van Den Berg, H. A.; Wemyss, A. M.; Roper, D. I.; Rodger, A . Beyond the discovery void: new targets for antibacterial compounds . Sci. Prog. , 2016 . 99 153 - 182 . DOI: 10.3184/003685016X14616130512308 http://doi.org/10.3184/003685016X14616130512308 .

Shen, S.; Huang, Y.; Yuan, A.; Lv, F.; Liu, L.; Wang, S . Electrochemical regulation of antibacterial activity using ferrocene-containing antibiotics . CCS Chem. , 2021 . 3 129 - 135 . DOI: 10.31635/ccschem.021.202000570 http://doi.org/10.31635/ccschem.021.202000570 .

Duval, R . E.; Grare, M.; Demore, B. Fight against antimicrobial resistance: we always need new antibacterials but for right bacteria . Molecules , 2019 . 24 9 .

Blaskovich, M. A. T . The fight against antimicrobial resistance is confounded by a global increase in antibiotic usage . ACS Infect. Dis. , 2018 . 4 868 - 870 . DOI: 10.1021/acsinfecdis.8b00109 http://doi.org/10.1021/acsinfecdis.8b00109 .

Luong, H. X.; Thanh, T. T.; Tran, T. H . Antimicrobial peptides–advances in development of therapeutic applications . Life Sci. , 2020 . 260 118407 DOI: 10.1016/j.lfs.2020.118407 http://doi.org/10.1016/j.lfs.2020.118407 .

Xie, X.; Gao, B.; Ma, Z.; Liu, J.; Zhang, J.; Liang, J.; Chen, Z.; Wu, L.; Li, W . Host–guest interaction driven peptide assembly into photoresponsive two-dimensional nanosheets with switchable antibacterial activity . CCS Chem. , 2021 . 3 1949 - 1962 . DOI: 10.31635/ccschem.020.202000312 http://doi.org/10.31635/ccschem.020.202000312 .

Cruz, J.; Ortiz, C.; Guzman, F.; Fernandez-Lafuente, R.; Torres, R . Antimicrobial peptides: promising compounds against pathogenic microorganisms . Curr. Med. Chem. , 2014 . 21 2299 - 2321 . DOI: 10.2174/0929867321666140217110155 http://doi.org/10.2174/0929867321666140217110155 .

Hancock, R. E. W.; Sahl, H. G . Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies . Nat. Biotechnol. , 2006 . 24 1551 - 1557 . DOI: 10.1038/nbt1267 http://doi.org/10.1038/nbt1267 .

Da Costa, J . P.; Cova, M.; Ferreira, R.; Vitorino, R. Antimicrobial peptides: an alternative for innovative medicines . Appl. Microbiol. Biot. , 2015 . 99 2023 - 2040 . DOI: 10.1007/s00253-015-6375-x http://doi.org/10.1007/s00253-015-6375-x .

Wang, J. J.; Dou, X. J.; Song, J.; Lyu, Y. F.; Zhu, X.; Xu, L.; Li, W. Z.; Shan, A. S . Antimicrobial peptides: promising alternatives in the post feeding antibiotic era . Med. Res. Rev. , 2019 . 39 831 - 859 . DOI: 10.1002/med.21542 http://doi.org/10.1002/med.21542 .

Kawano, Y.; Jordan, O.; Hanawa, T.; Borchard, G.; Patrulea, V . Are antimicrobial peptide dendrimers an Escape from ESKAPE . Adv. Wound Care , 2020 . 9 378 - 395 . DOI: 10.1089/wound.2019.1113 http://doi.org/10.1089/wound.2019.1113 .

Ciornei, C . D.; Sigurdardottir, T.; Schmidtchen, A.; Bodelsson, M. Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37 . Antimicrob. Agents Chemother. , 2005 . 49 2845 - 2850 . DOI: 10.1128/AAC.49.7.2845-2850.2005 http://doi.org/10.1128/AAC.49.7.2845-2850.2005 .

Hartlieb, M.; Williams, E. G. L.; Kuroki, A.; Perrier, S.; Locock, K. E. S . Antimicrobial polymers: mimicking amino acid functionality, sequence control and three-dimensional structure of host-defense peptides . Curr. Med. Chem. , 2017 . 24 2115 - 2140 . .

Salas-Ambrosio, P.; Tronnet, A.; Verhaeghe, P.; Bonduelle, C . Synthetic polypeptide polymers as simplified analogues of antimicrobial peptides . Biomacromolecules , 2021 . 22 57 - 75 . DOI: 10.1021/acs.biomac.0c00797 http://doi.org/10.1021/acs.biomac.0c00797 .

Shen, W.; He, P.; Xiao, C.; Chen, X . From antimicrobial peptides to antimicrobial poly(alpha-amino acid)s . Adv. Healthc. Mater. , 2018 . 7 1800354 DOI: 10.1002/adhm.201800354 http://doi.org/10.1002/adhm.201800354 .

Shima, S.; Matsuoka, H.; Iwamoto, T.; Sakai, H . Antibacterial action of epsilon-poly-L-lysine . J. Antibiot. , 1984 . 37 1449 - 1455 . DOI: 10.7164/antibiotics.37.1449 http://doi.org/10.7164/antibiotics.37.1449 .

Katchalski, E.; Grossfeld, I.; Frankel, M . Poly-condensation of alpha-amino acid derivatives. 3. Poly-lysine . J. Am. Chem. Soc. , 1948 . 70 2094 - 2101 . DOI: 10.1021/ja01186a032 http://doi.org/10.1021/ja01186a032 .

Katchalski, E.; Bichowskislomnitzki, L.; Volcani, B. E . The action of some water-soluble poly-alpha-amino acids on bacteria . Biochem. J. , 1953 . 55 671 - 680 . DOI: 10.1042/bj0550671 http://doi.org/10.1042/bj0550671 .

Mayandi, V.; Xi, Q. X.; Goh, E. T. L.; Koh, S. K.; Toh, T. Y. J.; Barathi, V. A.; Fazil, M.; Chalasani, M. L. S.; Varadarajan, J.; Ting, D. S. J.; Beuerman, R. W.; Chan, L. W.; Agrawal, R.; Barkham, T. M. S.; Zhou, L.; Verma, N . K.; Lakshminarayanan, R. Rational substitution of epsilon-lysine for alpha-lysine enhances the cell and membrane selectivity of pore-forming melittin . J. Med. Chem. , 2020 . 63 3522 - 3537 . DOI: 10.1021/acs.jmedchem.9b01846 http://doi.org/10.1021/acs.jmedchem.9b01846 .

Zhou, C. C.; Qi, X. B.; Li, P.; Chen, W. N.; Mouad, L.; Chang, M. W.; Leong, S. S. J.; Chan-Park, M. B . High potency and broad-spectrum antimicrobial peptides synthesized via ring-opening polymerization of alpha-aminoacid- N -carboxyanhydrides . Biomacromolecules , 2010 . 11 60 - 67 . DOI: 10.1021/bm900896h http://doi.org/10.1021/bm900896h .

Zhou, X.; Su, X.; Tan, Z.; Zhou, C . Synthesis of triblock amphiphilic copolypeptides with excellent antibacterial activity . Eur. Polym. J. , 2018 . 106 175 - 181 . DOI: 10.1016/j.eurpolymj.2018.07.017 http://doi.org/10.1016/j.eurpolymj.2018.07.017 .

Lam, S. J.; O'Brien-Simpson, N. M.; Pantarat, N.; Sulistio, A.; Wong, E. H.; Chen, Y. Y.; Lenzo, J. C.; Holden, J. A.; Blencowe, A.; Reynolds, E. C.; Qiao, G. G . Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers . Nat. Microbiol. , 2016 . 1 16162 DOI: 10.1038/nmicrobiol.2016.162 http://doi.org/10.1038/nmicrobiol.2016.162 .

Chen, Y. F.; Lai, Y. D.; Chang, C. H.; Tsai, Y. C.; Tang, C. C.; Jan, J. S . Star-shaped polypeptides exhibit potent antibacterial activities . Nanoscale , 2019 . 11 11696 - 11708 . DOI: 10.1039/C9NR02012H http://doi.org/10.1039/C9NR02012H .

Chen, S. J.; Huang, S. T.; Li, Y.; Zhou, C. C . Recent advances in epsilon-poly-L-lysine and L-lysine-based dendrimer synthesis, modification, and biomedical applications . Front. Chem. , 2021 . 9 14 .

Hyldgaard, M.; Mygind, T.; Vad, B. S.; Stenvang, M.; Otzen, D. E.; Meyer, R. L . The antimicrobial mechanism of action of epsilon-poly-L-lysine . Appl. Environ. Microbiol. , 2014 . 80 7758 - 7770 . DOI: 10.1128/AEM.02204-14 http://doi.org/10.1128/AEM.02204-14 .

Zou, Y. J.; He, S. S.; Du, J. Z . Epsilon-poly(L-lysine)-based hydrogels with fast-acting and prolonged antibacterial activities . Chinese J. Polym. Sci. , 2018 . 36 1239 - 1250 . DOI: 10.1007/s10118-018-2156-1 http://doi.org/10.1007/s10118-018-2156-1 .

Shi, C.; He, Y.; Feng, X. B.; Fu, D. H . Epsilon-polylysine and next-generation dendrigraft poly-L-lysine: chemistry, activity, and applications in biopharmaceuticals . J. Biomater. Sci., Polym. Ed. , 2015 . 26 1343 - 1356 . DOI: 10.1080/09205063.2015.1095023 http://doi.org/10.1080/09205063.2015.1095023 .

Liu, X.; Guo, J. W.; Liu, Y. D.; Liu, M.; Liu, H.; Han, M. M.; Ji, S. X . Antibacterial thermoplastic polyurethane/PL-DOSS composite films . Chinese J. Polym. Sci. , 2021 . 39 1020 - 1028 . DOI: 10.1007/s10118-021-2578-z http://doi.org/10.1007/s10118-021-2578-z .

Ye, R.; Xu, H.; Wan, C.; Peng, S.; Wang, L.; Xu, H.; Aguilar, Z . P.; Xiong, Y.; Zeng, Z.; Wei, H. Antibacterial activity and mechanism of action of ε -poly-L-lysine . Biochem. Biophys. Res. Commun. , 2013 . 439 148 - 153 . DOI: 10.1016/j.bbrc.2013.08.001 http://doi.org/10.1016/j.bbrc.2013.08.001 .

Shukla, S. C.; Singh, A.; Pandey, A. K.; Mishra, A . Review on production and medical applications of ɛ -polylysine . Biochem. Eng. J. , 2012 . 65 70 - 81 . DOI: 10.1016/j.bej.2012.04.001 http://doi.org/10.1016/j.bej.2012.04.001 .

Harada, K . Thermal homopolymerization of lysine and copolymerization with neutral and acidic amino acids . Bull. Chem. Soc. Jpn. , 1959 . 32 1007 - 1008 . DOI: 10.1246/bcsj.32.1007 http://doi.org/10.1246/bcsj.32.1007 .

Harada K; W., F. S . Characterization of thermal polymers of neutral α -amino acids with dicarboxylic amino acids or lysine . Arch. Biochem. Biophys. , 1965 . 109 49 - 56 . DOI: 10.1016/0003-9861(65)90285-7 http://doi.org/10.1016/0003-9861(65)90285-7 .

Scholl, M.; Kadlecova, Z.; Klok, H. A . Dendritic and hyperbranched polyamides . Prog. Polym. Sci. , 2009 . 34 24 - 61 . DOI: 10.1016/j.progpolymsci.2008.09.001 http://doi.org/10.1016/j.progpolymsci.2008.09.001 .

Liu, X.; Yang, Y.; Han, M.; Guo, J.; Liu, H.; Liu, Y.; Xu, J.; Ji, S.; Chen, X . Guanylated hyperbranched polylysines with high in vitro and in vivo antifungal activity . Adv. Healthc. Mater. , 2022 . 2201091 DOI: 10.1002/adhm.202201091 http://doi.org/10.1002/adhm.202201091 .

Kadlecova, Z.; Rajendra, Y.; Matasci, M.; Baldi, L.; Hacker, D. L.; Wurm, F. M.; Klok, H. A . DNA delivery with hyperbranched polylysine: a comparative study with linear and dendritic polylysine . J. Controlled Release , 2013 . 169 276 - 288 . DOI: 10.1016/j.jconrel.2013.01.019 http://doi.org/10.1016/j.jconrel.2013.01.019 .

Kadlecova, Z.; Baldi, L.; Hacker, D.; Wurm, F. M.; Klok, H. A . Comparative study on the in vitro cytotoxicity of linear, dendritic, and hyperbranched polylysine analogues . Biomacromolecules , 2012 . 13 3127 - 3137 . DOI: 10.1021/bm300930j http://doi.org/10.1021/bm300930j .

Thompson, M.; Scholz, C . Highly branched polymers based on poly(amino acid)s for biomedical application . Nanomaterials , 2021 . 11 23 .

Ramarao, N.; Nielsen-Leroux, C.; Lereclus, D . The insect Galleria mellonella as a powerful infection model to investigate bacterial pathogenesis . JoVE , 2012 . 70 4392 .

Balouiri, M.; Sadiki, M.; Ibnsouda, S. K . Methods for in vitro evaluating antimicrobial activity: a review . J. Pharm. Anal. , 2016 . 6 71 - 79 . DOI: 10.1016/j.jpha.2015.11.005 http://doi.org/10.1016/j.jpha.2015.11.005 .

Fischer, W. Lipoteichoic acid and lipids in the membrane of Staphylococcus aureus . Med. Microbiol. Immunol. 1994, 183 , 61-76.

Beveridge, T. J . Structures of gram-negative cell walls and their derived membrane vesicles . J. Bacteriol. , 1999 . 181 4725 - 4733 . DOI: 10.1128/JB.181.16.4725-4733.1999 http://doi.org/10.1128/JB.181.16.4725-4733.1999 .

Li, P.; Zhou, C.; Rayatpisheh, S.; Ye, K.; Poon, Y. F.; Hammond, P. T.; Duan, H.; Chan-Park, M. B . Cationic peptidopolysaccharides show excellent broad-spectrum antimicrobial activities and high selectivity . Adv. Mater. , 2012 . 24 4130 - 4137 . DOI: 10.1002/adma.201104186 http://doi.org/10.1002/adma.201104186 .

Lu, C.; Quan, G. L.; Su, M.; Nimmagadda, A.; Chen, W. D.; Pan, M.; Teng, P.; Yu, F. Y.; Liu, X.; Jiang, L.; Du, W. Y.; Hu, W.; Yao, F.; Pan, X.; Wu, C. B.; Liu, D. J.; Cai, J. F . Molecular architecture and charging effects enhance the in vitro and in vivo performance of multi-arm antimicrobial agents based on star-shaped poly(L-lysine) . Adv. Ther. , 2019 . 2 11 .

Yeaman, M. R.; Yount, N. Y. . Mechanisms of antimicrobial peptide action and resistance . Pharmacol. Rev. , 2003 . 55 27 - 55 . DOI: 10.1124/pr.55.1.2 http://doi.org/10.1124/pr.55.1.2 .

Nam, S. Y.; Lee, J.; Shin, S. S.; Yoo, H. J.; Yun, M.; Kim, S.; Kim, J. H.; Lee, J. H . Antibacterial and cytotoxic properties of star-shaped quaternary ammonium-functionalized polymers with different pendant groups . Polym. Chem. , 2022 . 13 1763 - 1773 . DOI: 10.1039/D2PY00007E http://doi.org/10.1039/D2PY00007E .

Al-Badri, Z. M.; Som, A.; Lyon, S.; Nelson, C. F.; Nusslein, K.; Tew, G. N . Investigating the effect of increasing charge density on the hemolytic activity of synthetic antimicrobial polymers . Biomacromolecules , 2008 . 9 2805 - 2810 . DOI: 10.1021/bm800569x http://doi.org/10.1021/bm800569x .

Palermo, E. F.; Kuroda, K . Structural determinants of antimicrobial activity in polymers which mimic host defense peptides . Appl. Microbiol. Biot. , 2010 . 87 1605 - 1615 . DOI: 10.1007/s00253-010-2687-z http://doi.org/10.1007/s00253-010-2687-z .

Li, P.; Poon, Y. F.; Li, W.; Zhu, H.-Y.; Yeap, S. H.; Cao, Y.; Qi, X.; Zhou, C.; Lamrani, M.; Beuerman, R. W.; Kang, E.-T.; Mu, Y.; Li, C. M.; Chang, M. W.; Jan Leong, S. S.; Chan-Park, M. B . A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability . Nat. Mater. , 2011 . 10 149 - 156 . DOI: 10.1038/nmat2915 http://doi.org/10.1038/nmat2915 .

Eisenberg, D.; Weiss, R. M.; Terwilliger, T. C.; Wilcox, W . Hydrophobic moments and protein-structure . Faraday Symp. Chem. Soc. , 1982 . 17 109 - 120 . DOI: 10.1039/fs9821700109 http://doi.org/10.1039/fs9821700109 .

Van den Bergen, G.; Stroet, M.; Caron, B.; Poger, D.; Mark, A. E . Curved or linear? Predicting the 3-dimensional structure of α -helical antimicrobial peptides in an amphipathic environment . FEBS Lett. , 2020 . 594 1062 - 1080 . DOI: 10.1002/1873-3468.13705 http://doi.org/10.1002/1873-3468.13705 .

Su, X.; Zhou, X.; Tan, Z.; Zhou, C . Highly efficient antibacterial diblock copolypeptides based on lysine and phenylalanine . Biopolymers , 2017 . 107 23041 DOI: 10.1002/bip.23041 http://doi.org/10.1002/bip.23041 .

Ramamourthy, G.; Park, J.; Seo, C.; Vogel, H. J.; Park, Y. Antifungal and antibiofilm activities and the mechanism of action of repeating lysine-tryptophan peptides against Candida albicans . Microorganisms 2020, 8 , 22.

Kuroda, K.; Caputo, G. A.; DeGrado, W. F . The role of hydrophobicity in the antimicrobial and hemolytic activities of polymethacrylate derivatives . Chem. Eur. J. , 2009 . 15 1123 - 1133 . DOI: 10.1002/chem.200801523 http://doi.org/10.1002/chem.200801523 .

Zasloff, M . Antimicrobial peptides of multicellular organisms . Nature , 2002 . 415 389 - 395 . DOI: 10.1038/415389a http://doi.org/10.1038/415389a .

Lienkamp, K.; Madkour, A. E.; Kumar, K. N.; Nüsslein, K.; Tew, G. N . Antimicrobial polymers prepared by ring-opening metathesis polymerization: manipulating antimicrobial properties by organic counterion and charge density variation . Chem. Eur. J. , 2009 . 15 11715 - 11722 . DOI: 10.1002/chem.200900606 http://doi.org/10.1002/chem.200900606 .

Chen, L. C.; Kung, S. K.; Chen, H. H.; Lin, S. B . Evaluation of zeta potential difference as an indicator for antibacterial strength of low molecular weight chitosan . Carbohydr. Polym. , 2010 . 82 913 - 919 . DOI: 10.1016/j.carbpol.2010.06.017 http://doi.org/10.1016/j.carbpol.2010.06.017 .

Henkelman, S.; Rakhorst, G.; Blanton, J.; van Oeveren, W . Standardization of incubation conditions for hemolysis testing of biomaterials . Mater. Sci. Eng., C , 2009 . 29 1650 - 1654 . DOI: 10.1016/j.msec.2009.01.002 http://doi.org/10.1016/j.msec.2009.01.002 .

Ong, Z. Y. I.; Yang, C.; Cheng, W.; Voo, Z. X.; Chin, W.; Hedrick, J. L.; Yang, Y. Y . Biodegradable cationic poly(carbonates): effect of varying side chain hydrophobicity on key aspects of gene transfection . Acta Biomater. , 2017 . 54 201 - 211 . DOI: 10.1016/j.actbio.2017.03.027 http://doi.org/10.1016/j.actbio.2017.03.027 .

Chen, J.; Jiao, Z. X.; Lin, L.; Guo, Z. P.; Xu, C. N.; Li, Y. H.; Tian, H. Y.; Chen, X. S . Polylysine-modified polyethylenimines as siRNA carriers for effective tumor treatment . Chinese J. Polym. Sci. , 2015 . 33 830 - 837 . DOI: 10.1007/s10118-015-1632-0 http://doi.org/10.1007/s10118-015-1632-0 .

Monnery, B. D.; Wright, M.; Cavill, R.; Hoogenboom, R.; Shaunak, S.; Steinke, J. H. G.; Thanou, M . Cytotoxicity of polycations: relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity . Int. J. Pharm. , 2017 . 521 249 - 258 . DOI: 10.1016/j.ijpharm.2017.02.048 http://doi.org/10.1016/j.ijpharm.2017.02.048 .

Huang, M.; Khor, E.; Lim, L. Y . Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation . Pharm. Res. , 2004 . 21 344 - 353 . DOI: 10.1023/B:PHAM.0000016249.52831.a5 http://doi.org/10.1023/B:PHAM.0000016249.52831.a5 .

Colomer, A.; Pinazo, A.; Garcia, M. T.; Mitjans, M.; Vinardell, M. P.; Infante, M . R.; Martinez, V.; Perez, L. pH-sensitive surfactants from lysine: assessment of their cytotoxicity and environmental behavior . Langmuir , 2012 . 28 5900 - 5912 . DOI: 10.1021/la203974f http://doi.org/10.1021/la203974f .

Uppu, D.; Samaddar, S.; Hoque, J.; Konai, M. M.; Krishnamoorthy, P.; Shome, B. R.; Haldar, J . Side chain degradable cationic-amphiphilic polymers with tunable hydrophobicity show in vivo activity . Biomacromolecules , 2016 . 17 3094 - 3102 . DOI: 10.1021/acs.biomac.6b01057 http://doi.org/10.1021/acs.biomac.6b01057 .

Choksakulnimitr, S.; Masuda, S.; Tokuda, H.; Takakura, Y.; Hashida, M . In vitro cytotoxicity of macromolecules in different cell culture systems . J. Controlled Release , 1995 . 34 233 - 241 . DOI: 10.1016/0168-3659(95)00007-U http://doi.org/10.1016/0168-3659(95)00007-U .

Morgan, D. M.; Clover, J.; Pearson, J. D . Effects of synthetic polycations on leucine incorporation, lactate dehydrogenase release, and morphology of human umbilical vein endothelial cells . J. Cell Sci. , 1988 . 91 231 - 238 . DOI: 10.1242/jcs.91.2.231 http://doi.org/10.1242/jcs.91.2.231 .

Morgan, D. M.; Larvin, V. L.; Pearson, J. D . Biochemical characterisation of polycation-induced cytotoxicity to human vascular endothelial cells . J. Cell Sci. , 1989 . 94 553 - 559 . DOI: 10.1242/jcs.94.3.553 http://doi.org/10.1242/jcs.94.3.553 .

Frederiksen, N.; Hansen, P . R.; Zabicka, D.; Tomczak, M.; Urbas, M.; Domraceva, I.; Björkling, F.; Franzyk, H. Alternating cationic-hydrophobic peptide/peptoid hybrids: influence of hydrophobicity on antibacterial activity and cell selectivity . ChemMedChem , 2020 . 15 2544 - 2561 . DOI: 10.1002/cmdc.202000526 http://doi.org/10.1002/cmdc.202000526 .

Lee, J.; Kang, D.; Choi, J.; Huang, W.; Wadman, M.; Barron, A. E.; Seo, J . Effect of side chain hydrophobicity and cationic charge on antimicrobial activity and cytotoxicity of helical peptoids . Bioorg. Med. Chem. Lett. , 2018 . 28 170 - 173 . DOI: 10.1016/j.bmcl.2017.11.034 http://doi.org/10.1016/j.bmcl.2017.11.034 .

Lienkamp, K.; Kumar, K. N.; Som, A.; Nüsslein, K.; Tew, G. N . “Doubly selective” antimicrobial polymers: how do they differentiate between bacteria . Chem. Eur. J. , 2009 . 15 11710 - 11714 . DOI: 10.1002/chem.200802558 http://doi.org/10.1002/chem.200802558 .

Konaté, K.; Mavoungou, J. F.; Lepengué, A. N.; Aworet-Samseny, R. R. R.; Hilou, A.; Souza, A.; Dicko, M. H.; M’Batchi, B . Antibacterial activity against β- lactamase producing Methicillin and Ampicillin-resistants Staphylococcus aureus : fractional Inhibitory Concentration Index (FICI) determination . Ann. Clin. Microbiol. Antimicrob. , 2012 . 11 18 DOI: 10.1186/1476-0711-11-18 http://doi.org/10.1186/1476-0711-11-18 .

Kavanagh, K.; Reeves, E. P . Exploiting the potential of insects for in vivo pathogenicity testing of microbial pathogens . FEMS Microbiol. Rev. , 2004 . 28 101 - 112 . DOI: 10.1016/j.femsre.2003.09.002 http://doi.org/10.1016/j.femsre.2003.09.002 .

Desbois, A. P.; Coote, P. J . Wax moth larva ( Galleria mellonella ): an in vivo model for assessing the efficacy of antistaphylococcal agents . J. Antimicrob. Chemother. , 2011 . 66 1785 - 1790 . DOI: 10.1093/jac/dkr198 http://doi.org/10.1093/jac/dkr198 .

Gibreel, T. M.; Upton, M. Synthetic epidermicin NI01 can protect Galleria mellonella larvae from infection with Staphylococcus aureus . J. Antimicrob. Chemother. 2013, 68 , 2269-2273.

Brackman, G.; Cos, P.; Maes, L.; Nelis, H. J.; Coenye, T. Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo . Antimicrob. Agents Chemother. 2011, 55 , 2655-2661.

Peleg, A. Y.; Monga, D.; Pillai, S.; Mylonakis, E.; Moellering, R. C.; Eliopoulos, G. M . Reduced susceptibility to vancomycin influences pathogenicity in Staphylococcus aureus infection . J. Infect. Dis. , 2009 . 199 532 - 536 . DOI: 10.1086/596511 http://doi.org/10.1086/596511 .

Gao, W.; Chua, K.; Davies, J. K.; Newton, H. J.; Seemann, T.; Harrison, P. F.; Holmes, N. E.; Rhee, H. W.; Hong, J. I.; Hartland, E. L.; Stinear, T. P.; Howden, B. P . Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent Infection . PLoS Pathog. , 2010 . 6 100094 .

Peleg, A. Y.; Jara, S.; Monga, D.; Eliopoulos, G. M.; Moellering, R. C., Jr.; Mylonakis, E . Galleria mellonella as a model system to study Acinetobacter baumannii pathogenesis and therapeutics . Antimicrob. Agents Chemother. , 2009 . 53 2605 - 2609 . DOI: 10.1128/AAC.01533-08 http://doi.org/10.1128/AAC.01533-08 .

Tsai, C. J. Y.; Loh, J. M. S.; Proft, T . Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing . Virulence , 2016 . 7 214 - 229 . DOI: 10.1080/21505594.2015.1135289 http://doi.org/10.1080/21505594.2015.1135289 .

Zhang, X. X.; Yang, L.; Lu, X. Q.; Lv, Y.; Jiang, D.; Yu, Y.; Peng, Z.; Dong, Z. H . Characterization and property of dual-functional Zn-incorporated TiO 2 micro-arc oxidation coatings: the influence of current density . J. Alloys Compd. , 2019 . 810 151893 DOI: 10.1016/j.jallcom.2019.151893 http://doi.org/10.1016/j.jallcom.2019.151893 .

Ren, L.; Chen, J. X.; Lu, Q.; Wang, C. B.; Han, J.; Huang, K.; Pan, X. N.; Wu, H . Construction of high selectivity and antifouling nanofiltration membrane via incorporating macrocyclic molecules into active layer . J. Membr. Sci. , 2020 . 597 117641 DOI: 10.1016/j.memsci.2019.117641 http://doi.org/10.1016/j.memsci.2019.117641 .

Brogden, K. A . Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria . Nat. Rev. Microbiol. , 2005 . 3 238 - 250 . DOI: 10.1038/nrmicro1098 http://doi.org/10.1038/nrmicro1098 .

Takahashi, D.; Shukla, S . K.; Prakash, O.; Zhang, G. Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity . Biochimie , 2010 . 92 1236 - 1241 . DOI: 10.1016/j.biochi.2010.02.023 http://doi.org/10.1016/j.biochi.2010.02.023 .

Ganewatta, M. S.; Tang, C . Controlling macromolecular structures towards effective antimicrobial polymers . Polymer , 2015 . 63 A1 - A29 . DOI: 10.1016/j.polymer.2015.03.007 http://doi.org/10.1016/j.polymer.2015.03.007 .

Bechinger, B.; Gorr, S. U . Antimicrobial peptides: mechanisms of action and resistance . J. Dent. Res. , 2017 . 96 254 - 260 . DOI: 10.1177/0022034516679973 http://doi.org/10.1177/0022034516679973 .

Views

219

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Surface-engineered Cationic Copolymer Microspheres with Nano-multiple Humps Topography for Enhancing Antibacterial Efficacy

Facile Fabrication of Hyperbranched Polyacetal Quaternary Ammonium with pH-Responsive Curcumin Release for Synergistic Antibacterial Activity

Experimental Investigation of Graphene and TiO2 Reinforced Poly(vinyl alcohol)-based Fiber Metal Laminates

Energy Storage Performance of Supercapacitors with Polyelectrolyte Surface Coatings: Effects of Dielectric Contrast

Topology-regulated Co-assembly of Single Chain Polymer Nanoparticles and Block Copolymers into Hierarchical Micelle@Vesicle Composite Structures

Related Author

Peng-Fei Song

Yu-Feng He

Rong-Min Wang

Ya-Ping Zhang

Tian Li

Jun Li

Xiao-Qi Cheng

De-Cheng Wu

Related Institution

Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Institute of Polymers, College of Chemistry & Chemical Engineering, Northwest Normal University

Department of Biomedical Engineering, Southern University of Science and Technology

University of Chinese Academy of Sciences

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences

Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Department of Polymer Science and Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University

⁰