合成生物学 ›› 2022, Vol. 3 ›› Issue (4): 728-747.doi: 10.12211/2096-8280.2021-094
杨兆颖1,2, 张帆1,2, 郭建文1,2, 高卫平1
收稿日期:
2021-09-27
修回日期:
2021-11-11
出版日期:
2022-08-31
发布日期:
2022-09-08
通讯作者:
高卫平
作者简介:
基金资助:
Zhaoying YANG1,2, Fan ZHANG1,2, Jianwen GUO1,2, Weiping GAO1
Received:
2021-09-27
Revised:
2021-11-11
Online:
2022-08-31
Published:
2022-09-08
Contact:
Weiping GAO
摘要:
类弹性蛋白多肽(elastin-like polypeptide,ELP)是一种衍生于天然弹性蛋白,可人工合成的多肽聚合物。ELP具有特殊的温度响应性,它会随温度的变化表现出可逆相转变行为,并且当它与其他小分子或多肽偶联时,该温敏特性可以被充分保留。借助基因工程可以人工合成ELP与ELP融合蛋白,精确调控ELP的结构与功能,在其序列中添加反应性氨基酸或多肽。同时,ELP由天然氨基酸组成,其生物相容性好,易于生物降解,免疫原性低,无毒性作用。基于以上优势,ELP已被广泛应用于蛋白的表达纯化、体外诊断、药物递送和组织工程等生物医药领域。本文结合国内外研究报道,简要介绍了ELP的设计原理、理化特性和生物合成方法,并列举了一些ELP应用于药物递送系统中有代表性的工作,最后总结了该研究领域面临的挑战和问题。
中图分类号:
杨兆颖, 张帆, 郭建文, 高卫平. 类弹性蛋白多肽的生物合成及其药物递送应用[J]. 合成生物学, 2022, 3(4): 728-747, doi: 10.12211/2096-8280.2021-094.
Zhaoying YANG, Fan ZHANG, Jianwen GUO, Weiping GAO. Biosynthesis of elastin-like polypeptides and their applications in drug delivery[J]. Synthetic Biology Journal, 2022, 3(4): 728-747, doi: 10.12211/2096-8280.2021-094.
图4
温度响应性ELP的局部缓释(a,b)温度响应性药物-ELP融合蛋白、药物-ELP偶联物在高于相变温度后会发生相变,形成聚集体,经皮下注射原位形成储库,并以单分子形式缓释入血液循环系统;(c)药物ELP偶联物可以通过EPR效应进入肿瘤,然后被MMP-2在肿瘤中分裂成游离的IFNα和ELP(V),从而增强肿瘤的穿透性和抗肿瘤疗效[51];(d)以MTD皮下注射Cy5标记的IFNα-MMPS-ELP(V)、IFNα-MMPS-ELP(A)、IFNα-ELP(V)和IFNα后的小鼠活体荧光成像;(e,f)以MTD皮下注射IFNα-MMPS-ELP(V)、IFNα-MMPS-ELP(A)、IFNα-ELP(V)和IFNα的药物代谢动力学(e)和抗肿瘤治疗效果(f)
表1
ELP用于药物递送的实例
药物递送策略 | 应用 | ELP药物 | ELP序列信息 | 文献 |
---|---|---|---|---|
延长药物体内循环半衰期 | 髓样乳腺癌 | SynB1-ELP-DOX | (VPGXG)150 X=V5G3A2 | [ |
感染性休克 | NtTNF-VHHELP | (VPGXG)100 X=V5G3A2 | [ | |
淋巴瘤 | IFN-ELP | (VPGXG)90 X=V5G3A2 | [ | |
药物储库 | 2型糖尿病 | (GLP-1)-ELP | (GVGVP)120 | [ |
卵巢癌和黑色素瘤 | IFN-ELP | (VPGVG)90 | [ | |
胶质母细胞瘤 | IFN-ELP和替莫唑胺联合用药 | (VPGVG)90 | [ | |
黑色素瘤和卵巢癌 | IFN-MMPS-ELP | (VPGVG)90 | [ | |
创伤后关节炎 | xELP[IL-1Ra] | VPGKG(VPGVG)16~102 | [ | |
神经炎症 | ELP-curcumin | [VPGXG] L=60,80,160; X = V/I/E [1∶3∶1] | [ | |
骨损伤 | rhBMP-2-ELP | (VPGVG)40[(VPGVG)2(VPGCG)(VPGVG)2]2 | [ | |
热靶向治疗 | 卵巢癌、宫颈癌、人源咽鳞癌 | ELP1 | (VPGXG)150 X=V5G3A2 | [ |
两亲性自组装体 | 卵巢癌 | IFNα-ELPdiblock | ELP(A)48-ELP(V)48 | [ |
乳腺癌 | FKBP-ELP | G(Val-Pro-Gly-Ile-Gly)48(Val-Pro-Gly-Ser-Gly)48Y | [ | |
混合组装体 | 乳腺癌 | LHRH-ELP-DOX | (VPGXG)160 X=V1A8G7 | [ |
结肠癌 | ELP-(YG)6-(CGG)8-GEM | (VPGAG)160 | [ | |
乳腺癌 | DOXENC,M-ELP90A,120 | (VPGXG)120 X=A9V1 | [ | |
黑色素瘤 | DOX/PPy-ELP-F3 | (XGVPG)160 | [ | |
黑色素瘤、颈瘤、膀胱癌 | ELP-AuNP | (VPGVG)60 | [ | |
ELP水凝胶 | 骨再生 | CDEc | (VPGVG)120 | [ |
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