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Bioinspired chiral supramolecular hydrogels
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
Hydrogels are generally regarded as biocompatible materials for cell therapy, tissue engineering, drug delivery and many other biomedical applications. Recently, there has been a focus on a new generation of dynamic hydrogels that are capable of responding to artificial triggers and biological signals with great precision [1]. Among the stimuli to induce controlled degradation of hydrogels, light showed great advantages such as non-invasiveness as well as temporal and spatial control with high precision [2]. However, most photo-degradable hydrogels consist of o-nitrobenzyl or azobenzene, which require multi-step synthesis and tedious purification procedures. Here we developed a one-step method to form a light-responsive hydrogel with the properties of rapid forming and injectable for controlled drug release (Fig. 1). The hydrogel was composed of a fourarm poly(ethylene glycol) (PEG) bearing thiol terminal groups and 3,6dichloro-1,2,4,5-tetrazine. The hydrogel quickly formed in a buffer solution within 3 min upon mixing the two solutions by forming covalent cross-links and anticancer drugs could be encapsulated inside the hydrogels. Interestingly, the hydrogel could be degraded upon irradiation with a 365 nm ultraviolet (UV) light. A gel-sol phase transition was observed within 15 min upon UV exposure. Anticancer drug doxorubicin entrapped in the hydrogel could be released and efficiently kill surrounding cancer cells under UV light irradiation. This study provides a facile strategy for light-responsive hydrogels for controlled drug release.
Fig. 1. (a) Schematic illustration of UV light-triggered hydrogel degradation and drug release. (b) Chemical structure of the hydrogel components and the model anticancer drug doxorubicin. (c) The chemical reaction during hydrogel formation and lighttriggered gel degradation.
Keywords: hydrogel, light-responsive, PEG, drug delivery Acknowledgements We thank financial support from the National Natural Science Foundation of China (21474044) and the Shanghai Municipal Science and Technology Commission (148014518).
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Bioinspired chiral supramolecular hydrogels Chuanliang Feng⁎, Guofeng Liu State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China ⁎Corresponding author. E-mail address: [email protected] (C. Feng) Chirality is one of life’s most distinctive biochemical signatures and has great influence on many biological events, e.g. maintaining normal functions for living cells. It reveals that cells can sense surface chiral molecules to show differential behaviors on enantiomorphous surfaces. So far, the researches are mainly confined to the role of molecular chirality on two dimensional (2D) surface and a lot of questions remain to be answered. Among them, how nanofibrous chirality influences cell behaviors in three dimensional (3D) extracellular matrices (ECM) is especially important, since it is only the 3D ECM nanofibrous structure can really mimick the necessary biophysical environment for tissue engineering and helical nanofibrous structure is closely related with relevant biological events. To explore this, supramolecular gelators are of particular interest candidate because their assembly arises from non–covalent interactions. With the rational design of chemical composition and molecular structures, surpramolecular gelators can be efficiently self-assemble into two or three dimensional microstructures, showing a big potential as biomimetic scaffold for multi-dimensional cell culture. With variation of physical or chemical properties, the chiral structures with the varied surface composition, mechanical strength, and surface wettability can be constructed and chirality regulated cell adhesion can be obtained in 3D (Fig. 1). Moreover, a smart control of cell adhesion is also realized by applying external fields, such as light, pH and so on. Typically, to visualize the interaction between chiral nanofibers and cells, supramolecular gelators with fluorescent emission are also designed. The study paves a way to explore the influence of chiraity of nanostructures on cell behaviors cell culture in 3D chiral environments.
Fig. 1. (a) Molecular structures of left handed chiral gelators (LPH) and right handed chiral gelators (DPH); (b) CD spectra of chiral gelators and their assembled nanofibers; (c) SEM images of LPH and DPH nanofibers; (d) Cells proliferation in LPH and DPH hydrogels, respectively, the enhanced cell proliferation in LPH hydrogels was achieved.
Keywords: gelators, hydrogels, chirality, self-assembly, cells Acknowledgements This work is supported by the National Natural Science Foundation of China (51573092, 51273111, 51173105).
References [1] J.A. Burdick, W.L. Murphy, Moving from static to dynamic complexity in hydrogel design, Nat. Commun. 3 (2012) 1269-1276. [2] X.Y. Wang, C.P. Wang, Q. Zhang, Y.Y. Cheng, Near infrared light-responsive and injectable supramolecular hydrogels for on-demand drug delivery, Chem. Comm. 52 (2016) 978-981.
doi:10.1016/j.jconrel.2017.03.067
References [1] G. F. Liu, D. Zhang, C. L. Feng, The nanofibers' chirality controlled three dimensional cell adhesion, Angew. Chem. Int. Ed. 53 (2014) 7789-7793. [2] G. F. Liu, L. Y. Zhu, W. Ji, C. L. Feng, Z. X. Wei, Achiral molecules triggered supramolecular chirality inversion of nanofibrous structures through co-assembly, Angew. Chem. Int. Ed. 55 (2015) 2411-2415.
doi:10.1016/j.jconrel.2017.03.068
Hydrogels are generally regarded as biocompatible materials for cell therapy, tissue engineering, drug delivery and many other biomedical applications. Recently, there has been a focus on a new generation of dynamic hydrogels that are capable of responding to artificial triggers and biological signals with great precision [1]. Among the stimuli to induce controlled degradation of hydrogels, light showed great advantages such as non-invasiveness as well as temporal and spatial control with high precision [2]. However, most photo-degradable hydrogels consist of o-nitrobenzyl or azobenzene, which require multi-step synthesis and tedious purification procedures. Here we developed a one-step method to form a light-responsive hydrogel with the properties of rapid forming and injectable for controlled drug release (Fig. 1). The hydrogel was composed of a fourarm poly(ethylene glycol) (PEG) bearing thiol terminal groups and 3,6dichloro-1,2,4,5-tetrazine. The hydrogel quickly formed in a buffer solution within 3 min upon mixing the two solutions by forming covalent cross-links and anticancer drugs could be encapsulated inside the hydrogels. Interestingly, the hydrogel could be degraded upon irradiation with a 365 nm ultraviolet (UV) light. A gel-sol phase transition was observed within 15 min upon UV exposure. Anticancer drug doxorubicin entrapped in the hydrogel could be released and efficiently kill surrounding cancer cells under UV light irradiation. This study provides a facile strategy for light-responsive hydrogels for controlled drug release.
Fig. 1. (a) Schematic illustration of UV light-triggered hydrogel degradation and drug release. (b) Chemical structure of the hydrogel components and the model anticancer drug doxorubicin. (c) The chemical reaction during hydrogel formation and lighttriggered gel degradation.
Keywords: hydrogel, light-responsive, PEG, drug delivery Acknowledgements We thank financial support from the National Natural Science Foundation of China (21474044) and the Shanghai Municipal Science and Technology Commission (148014518).
e19
Bioinspired chiral supramolecular hydrogels Chuanliang Feng⁎, Guofeng Liu State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China ⁎Corresponding author. E-mail address: [email protected] (C. Feng) Chirality is one of life’s most distinctive biochemical signatures and has great influence on many biological events, e.g. maintaining normal functions for living cells. It reveals that cells can sense surface chiral molecules to show differential behaviors on enantiomorphous surfaces. So far, the researches are mainly confined to the role of molecular chirality on two dimensional (2D) surface and a lot of questions remain to be answered. Among them, how nanofibrous chirality influences cell behaviors in three dimensional (3D) extracellular matrices (ECM) is especially important, since it is only the 3D ECM nanofibrous structure can really mimick the necessary biophysical environment for tissue engineering and helical nanofibrous structure is closely related with relevant biological events. To explore this, supramolecular gelators are of particular interest candidate because their assembly arises from non–covalent interactions. With the rational design of chemical composition and molecular structures, surpramolecular gelators can be efficiently self-assemble into two or three dimensional microstructures, showing a big potential as biomimetic scaffold for multi-dimensional cell culture. With variation of physical or chemical properties, the chiral structures with the varied surface composition, mechanical strength, and surface wettability can be constructed and chirality regulated cell adhesion can be obtained in 3D (Fig. 1). Moreover, a smart control of cell adhesion is also realized by applying external fields, such as light, pH and so on. Typically, to visualize the interaction between chiral nanofibers and cells, supramolecular gelators with fluorescent emission are also designed. The study paves a way to explore the influence of chiraity of nanostructures on cell behaviors cell culture in 3D chiral environments.
Fig. 1. (a) Molecular structures of left handed chiral gelators (LPH) and right handed chiral gelators (DPH); (b) CD spectra of chiral gelators and their assembled nanofibers; (c) SEM images of LPH and DPH nanofibers; (d) Cells proliferation in LPH and DPH hydrogels, respectively, the enhanced cell proliferation in LPH hydrogels was achieved.
Keywords: gelators, hydrogels, chirality, self-assembly, cells Acknowledgements This work is supported by the National Natural Science Foundation of China (51573092, 51273111, 51173105).
References [1] J.A. Burdick, W.L. Murphy, Moving from static to dynamic complexity in hydrogel design, Nat. Commun. 3 (2012) 1269-1276. [2] X.Y. Wang, C.P. Wang, Q. Zhang, Y.Y. Cheng, Near infrared light-responsive and injectable supramolecular hydrogels for on-demand drug delivery, Chem. Comm. 52 (2016) 978-981.
doi:10.1016/j.jconrel.2017.03.067
References [1] G. F. Liu, D. Zhang, C. L. Feng, The nanofibers' chirality controlled three dimensional cell adhesion, Angew. Chem. Int. Ed. 53 (2014) 7789-7793. [2] G. F. Liu, L. Y. Zhu, W. Ji, C. L. Feng, Z. X. Wei, Achiral molecules triggered supramolecular chirality inversion of nanofibrous structures through co-assembly, Angew. Chem. Int. Ed. 55 (2015) 2411-2415.
doi:10.1016/j.jconrel.2017.03.068