Abstract
A series of thermoresponsive cationic dendronized copolymers and their corresponding nanogels containing dendritic oligoethylene glycol (OEG) units and guanidine groups were prepared, and their complexation, protection, and release of nucleic acids were investigated. The dendritic OEGs endow these copolymer materials with good biocompatibility and characteristic thermoresponsiveness, while cationic guanidine groups can efficiently bind with the nucleic acids. The dendritic topology also affords the copolymers specific shielding effect which plays an essential role in protecting the activity of nucleic acids. At room temperature, dendronized copolymers and the corresponding nanogels could efficiently capture and condense the nucleic acids, while above their cloud points (Tcps), more than 75% of siRNA could be released in 1 h triggered by ATP. More importantly, the copolymer showed protective capability to siRNA, while nanogels exhibit even better protection when compared to the copolymers due to the synergetic effect from the three-dimensional cross-linked network and high density of dendritic units in vicinity. This kind of smart dendronized copolymer nanogels form a novel class of scaffolds as promising materials for biomedical applications.
Similar content being viewed by others
References
Zan, G.; Wu, Q. Biomimetic and bioinspired synthesis of nanomaterials/nanostructures. Adv. Mater.2016, 28, 2099–2147.
Trzebicka, B.; Szweda, R.; Kosowski, D.; Szweda, D.; Otulakowski, Ł.; Haladjova, E.; Dworak, A. Thermoresponsive polymerpeptide/protein conjugates. Prog. Polym. Sci.2017, 68, 35–76.
Wu, Y.; Ng, D. Y.; Kuan, S. L.; Weil, T. Protein-polymer therapeutics: a macromolecular perspective. Biomater. Sci.2015, 3, 214–230.
Zhu, J.; Zhang, Y.; Lu, D.; Zare, R. N.; Ge, J.; Liu, Z. Temperature-responsive enzyme-polymer nanoconjugates with enhanced catalytic activities in organic media. Chem. Commun.2013, 49, 6090–6092.
Wang, B.; Ma, R.; Liu, G.; Li, Y.; Liu, X.; An, Y.; Shi, L. Glucose-responsive micelles from self-assembly of poly(ethylene glycol)-b-poly(acrylic acid-co-acrylamidophenylboronic acid) and the controlled release of insulin. Langmuir2009, 25, 12522–12528.
Liu, J.; Pang, Y.; Huang, W.; Zhu, Z.; Zhu, X.; Zhou, Y.; Yan, D. Redox-responsive polyphosphate nanosized assemblies: a smart drug delivery platform for cancer therapy. Biomacromolecules2011, 12, 2407–2415.
Mogaki, R.; Hashim, P. K.; Okuro, K.; Aida, T. Guanidinium-based “molecular glues” for modulation of biomolecular functions. Chem. Soc. Rev.2017, 46, 6480–6491.
Yu, S.; Chen, J.; Dong, R.; Su, Y.; Ji, B.; Zhou, Y.; Zhu, X.; Yan, D. Enhanced gene transfection efficiency of PDMAEMA by incorporating hydrophobic hyperbranched polymer cores: effect of degree of branching. Polym. Chem.2012, 3, 3324–3329.
Yang, J.; Zhang, Q.; Chang, H.; Cheng, Y. Sufaace-engineered dendrimers in gene delivery. Chem. Rev.2015, 115, 5274–300.
Feng, C.; Huang, X. Polymer brushes: efficient synthesis and applications. Acc. Chem. Res.2018, 51, 2314–2323.
Huang, X.; Yin, Y.; Tang, Y.; Bai, X.; Zhang, Z.; Xu, J.; Liu, J.; Shen, J. Smart microgel catalyst with modulatory glutathione peroxidase activity. Soft Matter2009, 5, 1905–1911.
Liu, F.; Cui, Y.; Wang, L.; Wang, H.; Yuan, Y.; Pan, J.; Chen, H.; Yuan, L. Temperature-responsive poly(N-sopropylacrylamide) modified gold nanoparticle-protein conjugates for bioactivity modulation. ACS Appl. Mater. Interfaces2015, 7, 11547–11554.
Li, F.; Gao, Q.; Yang, M.; Guo, W. Regulation of catalytic DNA activities with thermosensitive gold nanoparticle surfaces. Langmuir2018, 34, 14932–14939.
Yoshimatsu, K.; Lesel, B. K.; Yonamine, Y.; Beierle, J. M.; Hoshino, Y.; Shea, K. J. Temperature-responsive “catch and release” of proteins by using multifunctional polymer-based nanoparticles. Angew. Chem. Int. Ed.2012, 51, 2405–2408.
Raynal, M.; Ballester, P.; Vidal-Ferran, A.; van Leeuwen, P. W. Supramolecular catalysis. Part 2: artificial enzyme mimics. Chem. Soc. Rev.2014, 43, 1734–1787.
Shi, H.; Liu, Y.; Qu, R.; Li, Y.; Ma, R.; An, Y.; Shi, L. A facile one-pot method to prepare peroxidase-like nanogel artificial enzymes for highly efficient and controllable catalysis. Colloid Surf. B-Biointerfaces2019, 174, 352–359.
Schlüter, A. D.; Rab, J. P. Dendronized polymers: synthesis, characterization, assembly at interfaces, and manipulation. Angew. Chem. Int. Ed.2000, 39, 864–883.
Chen, Y.; Xiong, X. Tailoring dendronized polymers. Chem. Commun.2010, 46, 5049–5060.
Fuhrmann, G.; Grotzky, A.; Lukic, R.; Matoori, S.; Luciani, P.; Yu, H.; Zhang, B.; Walde, P.; Schluter, A. D.; Gauthier, M. A.; Leroux, J. C. Sustained gastrointestinal activity of dendronized polymerenzyme conjugates. Nat. Chem.2013, 5, 582–589.
Zeng, H.; Little, H. C.; Tiambeng, T. N.; Williams, G. A.; Guan, Z. Multifunctional dendronized peptide polymer platform for safe and effective siRNA delivery. J. Am. Chem. Soc.2013, 155, 4962–4965.
Junk, M. J.; Li, W.; Schluter, A. D.; Wegner, G.; Spiess, H. W.; Zhang, A.; Hinderberger, D. EPR spectroscopic characterization of local nanoscopic heterogeneities during the thermal collapse of thermoresponsive dendronized polymers. Angew. Chem. Int. Ed.2010, 49, 5683–5687.
Liu, L.; Li, W.; Liu, K.; Yan, J.; Hu, G.; Zhang, A. Comblike thermoresponsive polymers with sharp transitions: synthesis, characterization, and their use as sensitive colorimetric sensors. Macromolecules2011, 44, 8614–8621.
Feng, X.; Liu, J.; Xu, G.; Zhang, X.; Su, X.; Li, W.; Zhang, A. Thermoresponsive double network cryogels from dendronized copolymers showing tunable encapsulation and release of proteins. J. Mater. Chem. B2018, 6, 1903–1911.
Zhou, C.; Abdel-Rahman, M. A.; Li, W.; Liu, K.; Zhang, A. Thermoresponsive dendronized copolymers for protein recognitions based on biotin-avidin interaction. Chin. Chem. Lett.2017, 28, 832–838.
Yan, J.; Liu, K.; Li, W.; Shi, H.; Zhang, A. Thermoresponsive dendronized polypeptides showing switchable recognition to catechols. Macromolecules2016, 49, 510–517.
Stanzl, E. G.; Trantow, B. M.; Vargas, J. R.; Wender, P. A. Fifteen years of cell-penetrating, guanidinium-rich molecular transporters: basic science, research tools, and clinical applications. Acc. Chem. Res.2013, 46, 2944–2954.
Li, W.; Zhang, A.; Feldman, K.; Walde, P.; Schluter, A. D. Thermoresponsive dendronized polymers. Macromolecules2010, 41, 3659–3667.
Funhoff, A. M.; van Nostrum, C. F.; Lok, M. C.; Fretz, M. M.; Crommelin, D. J. A.; Hennink, W. E. ooly(3-gunnidmopropyl methacrylate): a novel cationic polymer for gene delivery. Bioconjugate Chem.2004, 15, 1212–1220.
Biltresse, S.; Attolini, M.; Dive, G.; Cordi, A.; Tucker, G. C.; Marchand-Brynaert, J. Novel RGD-like molecules based on the tyrosine template: design, synthesis, and biological evaluation on isolated integrins αvβ3/α∥bβ3 and in cellular adhesion tests. Bioorg. Med. Chem.2004, 12, 5379–5393.
Li, W.; Zhang, A.; Schluter, A. D. Thermoresponsive dendronized polymers with tunable lower critical solution temperatures. Chem. Commun.2008, 5523–5525.
Ping, Y.; Liu, C.; Zhang, Z.; Liu, K. L.; Chen, J.; Li, J. Chitosan-graft-(PEI-β-cyclodextrin) copolymers and their supramolecular PEGylation for DNA and siRNA delivery. Biomaterials2011, 32, 8328–8341.
Liu, L.; Li, W.; Yan, J.; Zhang, A. Thermoresponsive dendronized polymeric sensors. J. Polym. Sci., Part A: Polym. Chem.2014, 52, 1706–1713.
Di Virgilio, F. Dr. Jekyll/Mr. Hyde: the dual role of extracellular ATP. J. Auton. Nerv. Syst.2000, 81, 59–63.
Cheng, Q.; Huang, Y.; Zheng, H.; Wei, T.; Zheng, S.; Huo, S.; Wang, X.; Du, Q.; Zhang, X.; Zhang, H. Y.; Liang, X. J.; Wang, C.; Tang, R.; Liang, Z. The effect of guanidinylation of PEGylated poly(2-aminoethyl methacrylate) on the systemic delivery of siRNA. Biomaterials2013, 34, 3120–3131.
Okuro, K.; Sasaki, M.; Aida, T. Boronic acid-appended molecular glues for ATP-responsive activity modulation of enzymes. J. Am. Chem. Soc.2016, 138, 5527–5530.
Acknowledgments
We sincerely thank Dr. Hongmei Deng from the Instrumental Analysis and Research Center of Shanghai University for her assistance with NMR measurements. This work was financially supported by the National Natural Science Foundation of China (Nos. 21971161, 21971160, and 21574078), Shanghai Pujiang Program (No. 19PJ1403700), and Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning.
Author information
Authors and Affiliations
Corresponding authors
Electronic Supplementary Information
Rights and permissions
About this article
Cite this article
Yao, Y., Wu, JH., Cao, SJ. et al. Thermoresponsive Nanogels from Dendronized Copolymers for Complexation, Protection and Release of Nucleic Acids. Chin J Polym Sci 38, 1164–1170 (2020). https://doi.org/10.1007/s10118-020-2452-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10118-020-2452-4