Dynamic Imine Bonding Facilitates Mannan Release from a Nanofibrous Peptide Hydrogel.
Dynamic Imine Bonding Facilitates Mannan Release from a Nanofibrous Peptide Hydrogel.
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DOI：
10.1021/acs.bioconjchem.2c00461
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发表时间：
2023-01-18
影响因子：
4.7
通讯作者：
McHugh KJ
中科院分区：
文献类型：
--
作者：
Pogostin BH;Saenz G;Cole CC;Euliano EM;Hartgerink JD;McHugh KJ
最近，人们对使用甘露聚糖作为免疫调节生物缀合物的兴趣增加。尽管甘露聚糖的还原（R-Man）和氧化（O-Man）形式之间存在显著的免疫学和功能差异，但关于甘露聚糖氧化态对其体内持久性的影响或其从生物材料中潜在的控制释放（可改善免疫或预防功效）的影响知之甚少。在这里，我们研究了氧化态对甘露聚糖从生物相容性和免疫刺激性多结构域肽水凝胶K2（SL）6 K2（缩写为K2）中体外和体内释放的影响，该水凝胶先前已用于蛋白质和小分子有效载荷的控释。我们观察到O-Man在体外从K2水凝胶中的释放比R-Man慢。在体内，O-Man从K2水凝胶中的清除比O-Man单独的清除慢。我们将较慢的释放速率归因于O-Man上的反应性醛基与K2上的赖氨酸残基之间形成动态亚胺键。还观察到这种亚胺相互作用改善了K2 + O-Man水凝胶强度和剪切恢复，而不显著影响二级结构或肽的形成。在K2中加载的O-Man、K2中加载的R-Man和单独的R-Man的体内释放速率中没有观察到差异。这些数据表明，在皮下注射后，R-Man在体内比O-Man自然持续更长时间，并且与肽水凝胶的相互作用最小。这些结果突出了O-Man和R-Man的体内行为的潜在关键的但先前未报道的差异，并证明K2可用于使O-Man的释放相对于R-Man的释放标准化。O-Man和K2的组合可用于增强O-Man的免疫刺激作用。用于传染病疫苗和癌症免疫治疗等应用。
Recently, there has been increased interest in using mannan as an immunomodulatory bioconjugate. Despite notable immunological and functional differences between the reduced (R-Man) and oxidized (O-Man) forms of mannan, little is known about the impact of mannan oxidation state on its in vivo persistence or its potential controlled release from biomaterials that may improve immunotherapeutic or prophylactic efficacy. Here, we investigate the impact of oxidation state on the in vitro and in vivo release of mannan from a biocompatible and immunostimulatory multidomain peptide hydrogel, K2(SL)6K2 (abbreviated as K2), that has been previously used for the controlled release of protein and small molecule payloads. We observed that O-Man released more slowly from K2 hydrogels in vitro than R-Man. In vivo, the clearance of O-Man from K2 hydrogels was slower than O-Man alone. We attributed the slower release rate to the formation of dynamic imine bonds between reactive aldehyde groups on O-Man and the lysine residues on K2. This imine interaction was also observed to improve K2 + O-Man hydrogel strength and shear recovery without significantly influencing secondary structure or peptide nanofiber formation. There were no observed differences in the in vivo release rates of O-Man loaded in K2, R-Man loaded in K2, and R-Man alone. These data suggest that, after subcutaneous injection, R-Man naturally persists longer in vivo than O-Man and minimally interacts with the peptide hydrogel. These results highlight a potentially critical, but previously unreported, difference in the in vivo behavior of O-Man and R-Man and demonstrate that K2 can be used to normalize the release of O-Man to that of R-Man. Further, since K2 itself is an adjuvant, a combination of O-Man and K2 could be used to enhance the immunostimulatory effects of O-Man for applications such as infectious disease vaccines and cancer immunotherapy.
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影响因子：
5.5
作者：
Cong Truc Huynh;Minh Khanh Nguyen;Lee, Doo Sung
通讯作者：
Lee, Doo Sung
影响因子：
17.1
作者：
Chakraborty, Priyadarshi;Guterman, Tom;Gazit, Ehud
通讯作者：
Gazit, Ehud
影响因子：
5.6
作者：
Caisova, Veronika;Uher, Ondrej;Zenka, Jan
通讯作者：
Zenka, Jan
影响因子：
4.3
作者：
Francois-Heude, Marc;Mendez-Ardoy, Alejandro;Djedaini-Pilard, Florence
通讯作者：
Djedaini-Pilard, Florence
DOI：
10.1016/j.jconrel.2018.01.027
发表时间：
2018-03-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Chen N;Johnson MM;Collier MA;Gallovic MD;Bachelder EM;Ainslie KM
通讯作者：
Ainslie KM