Manipulation of the dually thermoresponsive behavior of peptide-based vesicles through modification of collagen-like peptide domains
Manipulation of the dually thermoresponsive behavior of peptide-based vesicles through modification of collagen-like peptide domains
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DOI：
10.1002/btm2.10145
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发表时间：
2019-10-16
影响因子：
7.4
通讯作者：
Kiick, Kristi L.
中科院分区：
文献类型：
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作者：
Dunshee, Lucas C.;Sullivan, Millicent O.;Kiick, Kristi L.
响应于时间上限定的外源性线索的材料继续是对按需纳米颗粒药物递送应用的研究的积极追求，并且使用一种或多种外源性温度刺激可以显著扩展基于纳米颗粒的药物递送制剂在高温和低温条件下的应用。以前，我们已经报道了一种生物相容性和热响应性弹性蛋白-b-胶原蛋白样多肽（ELP-CLP）缀合物的开发，该缀合物能够自组装成囊泡并封装小分子治疗剂，该小分子治疗剂可以通过单一温度刺激以不同的速率递送。本文中，我们报告了多种ELP-CLP缀合物的评价，证明了ELP-CLP的逆转变温度（T-t）可以通过改变CLP结构域的解链温度（T-m）来操纵，并且ELP-CLP缀合物的总体亲水性也可以改变T-t。基于这些设计参数，我们证明了ELP-CLP序列（VPFG）（6）-（VPFG）（7）GG可以在25 ℃下自组装成稳定的囊泡，并在升高的温度下通过CLP结构域在其T-m以上的解折叠解离。我们还证明了在这里的第一次，这种ELP-CLP囊泡解离的能力，通过利用ELP中发现的逆转变温度（T-T）现象的手段，通过低温温度刺激。设计规则的开发，用于操纵这些生物共轭物的热性能将使未来的修改ELP或CLP序列，以更精细地调整特定的生物医学应用的共轭物的过渡。
Materials that respond to temporally defined exogenous cues continue to be an active pursuit of research toward on-demand nanoparticle drug delivery applications, and using one or more exogenous temperature stimuli could significantly expand the application of nanoparticle-based drug delivery formulations under both hyperthermal and hypothermal conditions. Previously we have reported the development of a biocompatible and thermoresponsive elastin-b-collagen-like polypeptide (ELP-CLP) conjugate that is capable of self-assembling into vesicles and encapsulating small molecule therapeutics that can be delivered at different rates via a single temperature stimulus. Herein we report the evaluation of multiple ELP-CLP conjugates, demonstrating that the inverse transition temperature (T-t) of the ELP-CLPs can be manipulated by modifying the melting temperature (T-m) of the CLP domain, and that the overall hydrophilicity of the ELP-CLP conjugate also may alter the T-t. Based on these design parameters, we demonstrate that the ELP-CLP sequence (VPGFG)(6)-(GPO)(7)GG can self-assemble into stable vesicles at 25 degrees C and dissociate at elevated temperatures by means of the unfolding of the CLP domain above its T-m. We also demonstrate here for the first time the ability of this ELP-CLP vesicle to dissociate via a hypothermic temperature stimulus by means of exploiting the inverse transition temperature (T-t) phenomena found in ELPs. The development of design rules for manipulating the thermal properties of these bioconjugates will enable future modifications to either the ELP or CLP sequences to more finely tune the transitions of the conjugates for specific biomedical applications.