新型葫芦[6]脲纳米颗粒超极化129Xe“分子笼”研究

doi:10.11938/cjmr20192742

波谱学杂志 ›› 2019, Vol. 36 ›› Issue (4): 472-480.doi: 10.11938/cjmr20192742

新型葫芦[6]脲纳米颗粒超极化¹²⁹Xe“分子笼”研究

袁晨露^1,2, 郭茜旎¹, 陈世桢¹, 周欣¹

1. 波谱与原子分子物理国家重点实验室, 武汉磁共振中心(中国科学院武汉物理与数学研究所), 湖北武汉 430071;
2. 中国科学院大学, 北京 100049

收稿日期:2019-04-26 出版日期:2019-12-05 发布日期:2019-05-30
通讯作者: 周欣 E-mail:xinzhou@wipm.ac.cn
基金资助:
国家自然科学基金资助项目（91859206，81625011）；国家重点研发计划（2016YFC1304704）；中国科学院前沿科学重点研究计划（QYZDY-SSWSLH018）.

A Novel Molecular Cage for Hyperpolarized ¹²⁹Xe Based on Cucurbit[6]uril Nanoparticles

YUAN Chen-lu^1,2, GUO Qian-ni¹, CHEN Shi-zhen¹, ZHOU Xin¹

1. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan(Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences), Wuhan 430071, China;
2. University of Chinese Academy of Sciences, Beijing 100049

Received:2019-04-26 Online:2019-12-05 Published:2019-05-30

摘要/Abstract

摘要： 在相同浓度下，超极化¹²⁹Xe的核磁共振（NMR）灵敏度是传统质子NMR的10 000倍以上，但单原子Xe不具有靶向性，只有单一NMR信号.若超极化¹²⁹Xe与“分子笼”相结合，就能获得新的“笼”内Xe信号，为发展超极化¹²⁹Xe分子探针奠定基础.因此，构建新型的“分子笼”是发展新型超极化¹²⁹Xe分子探针的一个重要方向.葫芦[6]脲纳米颗粒的出现能改善以葫芦[6]脲为主体的¹²⁹Xe分子探针水溶性差、信号弱等缺点.本文构建了水溶性的葫芦[6]脲纳米颗粒，并发现其具有葫芦[6]脲/纳米颗粒内部两个“笼”内¹²⁹Xe信号.这一发现使这种纳米颗粒具有成为超极化¹²⁹Xe分子探针的潜力，能降低检测结果中假阳性和假阴性的发生率，值得更深入的探索和研究.

关键词: 超极化¹²⁹Xe核磁共振, 双信号, 化学交换饱和转移(CEST), 纳米颗粒, 葫芦[6]脲

Abstract: Hyperpolarized ¹²⁹Xe NMR has a detection sensitivity up to 10 000 times higher than that in the conventional ¹H NMR. Hyperpolarized ¹²⁹Xe gas has only one NMR signal, but can produce multiple signals when combined with molecular cages, providing the chances to develop targeted molecular probes. In this paper, water-soluble cucurbit[6]uril nanoparticles were used for loading hyperpolarized ¹²⁹Xe gas to construct targeted molecular probes. It was observed that such molecular probes had double "cage" signals and the potential to be developed into multi-functional probes.

Key words: hyperpolarized ¹²⁹Xe nuclear magnetic resonance, chemical exchange saturation transfer (CEST), nanoparticle, cucurbit[6]uril

中图分类号:

O482.53

袁晨露, 郭茜旎, 陈世桢, 周欣. 新型葫芦[6]脲纳米颗粒超极化¹²⁹Xe“分子笼”研究[J]. 波谱学杂志, 2019, 36(4): 472-480.

YUAN Chen-lu, GUO Qian-ni, CHEN Shi-zhen, ZHOU Xin. A Novel Molecular Cage for Hyperpolarized ¹²⁹Xe Based on Cucurbit[6]uril Nanoparticles[J]. Chinese Journal of Magnetic Resonance, 2019, 36(4): 472-480.

参考文献

[1] TERRENO E, CASTELLI D D, VIATE A, et al. Challenges for molecular magnetic resonance imaging[J]. Chem Rev, 2010, 110(5):3019-3042.
[2] GAO D L, SUN P, ZHANG X, et al. Interactions between albumin and fatty acids studied by NMR spectroscopy[J]. Chinese J Magn Reson, 2018, 35(3):338-344. 高东莉, 孙鹏, 张许, 等. 运用NMR研究白蛋白与脂肪酸的相互作用[J]. 波谱学杂志, 2018, 35(3):338-344.
[3] PALANIAPPAN K K, FRANCIS M B, PINES A, et al. Molecular sensing using hyperpolarized xenon NMR spectroscopy[J]. Israel J Chem, 2014, 54(1/2):104-112.
[4] WALKER T, HAPPER W. Spin-exchange optical pumping of noble-gas nuclei[J]. Rev Mod Phys, 1997, 69(2):629-642.
[5] ZHOU X, SUN X P, LUO J, et al. Production of hyperpolarized Xe-129 gas without nitrogen by optical pumping at Cs-133 D-2 line in flow system[J]. Chin Phys Lett, 2004, 21(8):1501-1503.
[6] ZHOU X, GRAZIANI D, PINES A. Hyperpolarized xenon NMR and MRI signal amplification by gas extraction[J]. Proc Natl Acad Sci U S A, 2009, 106(40):16903-16906.
[7] ZHAO X C, SUN X P, ZHOU X, et al. Measuring polarization of hyperpolarized xenon-129 gas with low-field NMR[J]. Chinese J Magn Reson, 2016, 33(3):458-467. 赵修超, 孙献平, 周欣, 等. 超极化气体氙-129的低场NMR测量[J]. 波谱学杂志, 2016, 33(3):458-467.
[8] SCHLUNDT A, KILIAN W, BEYERMANN M, et al. A xenon-129 biosensor for monitoring MHC-peptide interactions[J]. Angew Chem Int Ed, 2009, 48(23):4142-4145.
[9] BOUTIN C, STOPIN A, LENDA F, et al. Cell uptake of a biosensor detected by hyperpolarized Xe-129 NMR:The transferrin case[J]. Bioorg Med Chem, 2011, 19(13):4135-4143.
[10] KOTERA N, DUBOST E, MILANOLE G, et al. A doubly responsive probe for the detection of Cys4-tagged proteins[J]. Chem Commun, 2015, 51(57):11482-11484.
[11] WEI Q, SEWARD G K, HILL P A, et al. Designing Xe-129 NMR biosensors for matrix metalloproteinase detection[J]. J Am Chem Soc, 2006, 128(40):13274-13283.
[12] CHAMBERS J M, HILL P A, AARON J A, et al. Cryptophane xenon-129 nuclear magnetic resonance biosensors targeting human carbonic anhydrase[J]. J Am Chem Soc, 2009, 131(2):563-569.
[13] ROY V, BROTIN T, DUTASTA J P, et al. A cryptophane biosensor for the detection of specific nucleotide targets through xenon NMR spectroscopy[J]. Chemphyschem, 2007, 8(14):2082-2085.
[14] KHAN N S, RIGGLE B A, SEWARD G K, et al. Cryptophane-folate biosensor for Xe-129 NMR[J]. Bioconjugate Chem, 2015, 26(1):101-109.
[15] PALANIAPPAN K K, RAMIREZ R M, BAJAJ V S, et al. Molecular imaging of cancer cells using a bacteriophage-based ¹²⁹Xe NMR biosensor[J]. Angew Chem Int Ed, 2013, 52(18):4849-4853.
[16] ROSSELLA F, ROSE H M, WITTE C, et al. Design and characterization of two bifunctional cryptophane A-based host molecules for xenon magnetic resonance imaging applications[J]. Chempluschem, 2014, 79(10):1463-1471.
[17] WITTE C, MARTOS V, ROSE H M, et al. Live-cell MRI with xenon Hyper-CEST biosensors targeted to metabolically labeled cell-surface glycans[J]. Angew Chem Int Ed, 2015, 54(9):2806-2810.
[18] ROSE H M, WITTE C, ROSSELLAA F, et al. Development of an antibody-based, modular biosensor for Xe-129 NMR molecular imaging of cells at nanomolar concentrations[J]. Proc Natl Acad Sci U S A, 2014, 111(32):11697-11702.
[19] YANG S J, JIANG W P, REN L L, et al. Biothiol xenon MRI sensor based on thiol-addition reaction[J]. Anal Chem, 2016, 88(11):5835-5840.
[20] BERTHAULT P, DESVAUX H, WENDLINGER T, et al. Effect of pH and counterions on the encapsulation properties of xenon in water-soluble cryptophanes[J]. Chem Eur J, 2010, 16(43):12941-12946.
[21] RIGGLE B A, WANG Y, DMOCHOWSKI I J. A "smart" Xe-129 NMR biosensor for pH-dependent cell labeling[J]. J Am Chem Soc, 2015, 137(16):5542-5548.
[22] KOTERA N, TASSALI N, LEONCE E, et al. A sensitive zinc-activated ¹²⁹Xe MRI probe[J]. Angew Chem Int Ed, 2012, 51(17):4100-4103.
[23] TASSALI N, KOTERA N, BOUTIN C, et al. Smart detection of toxic metal ions, Pb²⁺ and Cd²⁺, using a Xe-129 NMR-based sensor[J]. Anal Chem, 2014, 86(3):1783-1788.
[24] ZHANG J, JIANG W P, LUO Q, et al. Rational design of hyperpolarized xenon NMR molecular sensor for the selective and sensitive determination of zinc ions[J]. Talanta, 2014, 122:101-105.
[25] GUO Q N, ZENG Q B, JIANG W P, et al. A molecular imaging approach to mercury sensing based on hyperpolarized Xe-129 molecular clamp probe[J]. Chem Eur J, 2016, 22(12):3967-3970.
[26] WANG Y F, DMOCHOWSKI I J. An expanded palette of xenon-129 NMR biosensors[J]. Acc Chem Res, 2016, 49(10):2179-2187.
[27] KUNTH M, WITTE C, HENNIG A, et al. Identification, classification, and signal amplification capabilities of high-turnover gas binding hosts in ultra-sensitive NMR[J]. Chem Sci, 2015, 6(11):6069-6075.
[28] JON S Y, SELVAPALAM N, OH D H, et al. Facile synthesis of cucurbit[n]uril derivatives via direct functionalization:expanding utilization of cucurbit[n]uril[J]. J Am Chem Soc, 2003, 125(34):10186-10187.
[29] KIM K, SELVAPALAM N, KO Y H, et al. Functionalized cucurbiturils and their applications[J]. Chem Soc Rev, 2007, 36(2):267-279.
[30] LEE H K, PARK K M, JEON Y J, et al. Vesicle formed by amphiphilc cucurbit
[6]uril:versatile, noncovalent modification of the vesicle surface, and multivalent binding of sugar-decorated vesicles to lectin[J]. J Am Chem Soc, 2005, 127(14):5006-5007.
[31] KIM D, KIM E, KIM J, et al. Direct synthesis of polymer nanocapsules with a noncovalently tailorable surface[J]. Angew Chem Int Ed, 2007, 46(19):3471-3474.
[32] KIM D, KIM E, LEE J, et al. Direct synthesis of polymer nanocapsules:self-assembly of polymer hollow spheres through irreversible covalent bond formation[J]. J Am Chem Soc, 2010, 132(28):9908-9919.
[33] YUN G, HASSAN Z, LEE J, et al. Highly stable, water-dispersible metal-nanoparticle-decorated polymer nanocapsules and their catalytic applications[J]. Angew Chem Int Ed, 2014, 53(25):6414-6418.
[34] PARK K M, SUH K, JUNG H, et al. Cucurbituril-based nanoparticles:a new efficient vehicle for targeted intracellular delivery of hydrophobic drugs[J]. Chem Commun, 2009(1):71-73.
[35] AYHAN M M, KAROUI H, HARDY M, et al. Comprehensive synthesis of monohydroxy-cucurbit[n]urils (n=5,6,7,8):high purity and high conversions[J]. J Am Chem Soc, 2015, 137(32):10238-10245.
[36] STEVENS T K, RAMIREZ R M, PINES A. Nanoemulsion contrast agents with sub-picomolar sensitivity for xenon NMR[J]. J Am Chem Soc, 2013, 135(26):9576-9579.

新型葫芦[6]脲纳米颗粒超极化¹²⁹Xe“分子笼”研究

A Novel Molecular Cage for Hyperpolarized ¹²⁹Xe Based on Cucurbit[6]uril Nanoparticles

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 3

编辑推荐

Metrics

本文评价

[1]	魏国境, 易佩伟, 陶泉, 冯衍秋. CEST成像不同量化方式在急性帕金森氏病小鼠模型研究中的应用比较[J]. 波谱学杂志, 2019, 36(2): 195-207.
[2]	陶泉, 易佩伟, 魏国境, 冯衍秋. 基于CEST机制的pH成像方法、原理和应用[J]. 波谱学杂志, 2018, 35(4): 505-519.
[3]	杨永贵, 陈忠, 蔡聪波, 郭岗. 1.5 T磁共振化学交换饱和转移成像的影响因素分析[J]. 波谱学杂志, 2017, 34(3): 275-282.