Articles

Cathepsin B Triggered Hyperpolarization 129Xe MRI Probe for Ultra-Sensitive Lung Cancer Cells Detection

  • Chong-wu WANG ,
  • Xi HUANG ,
  • Lei SHI ,
  • Shi-zhen CHEN ,
  • Xin ZHOU
Expand
  • 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, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences), Wuhan 430071, China
    2. University of Chinese Academy of Sciences, Beijing 100049, China

Received date: 2020-04-25

  Online published: 2020-05-27

Abstract

Cathepsin B (Cat B) is a lysosomal cysteine protease that plays an essential role in cellular metabolism. Cat B is overexpressed in lung cancer cells. Fluorescence imaging techniques have been developed for measuring intracellular Cat B levels, which, however, suffers from limited penetration depth and interferences from autofluorescence background. To resolve these technical difficulties, we designed a novel Cat B biosensor detected by hyperpolarized xenon magnetic resonance imaging. It consists of a cryptophane cage as a 129Xe NMR reporter and an amide bond as a Cat B-specific cleavable group. When the biosensor interacts with Cat B, the cleavage of amide bond leads to changes in 129Xe chemical shift. Combing with hyperpolarization-chemical exchange saturation transfer (Hyper-CEST), our biosensor provides a novel method for responsive detection of Cat B.

Cite this article

Chong-wu WANG , Xi HUANG , Lei SHI , Shi-zhen CHEN , Xin ZHOU . Cathepsin B Triggered Hyperpolarization 129Xe MRI Probe for Ultra-Sensitive Lung Cancer Cells Detection[J]. Chinese Journal of Magnetic Resonance, 2021 , 38(3) : 336 -344 . DOI: 10.11938/cjmr20202828

References

1 López-otín C , Matrisian L M . Emerging roles of proteases in tumorsuppression[J]. Nat Rev Cancer, 2007, 7 (10): 800- 808.
2 Sinha A A , Jamuar M P , Wilson M J , et al. Plasma membrane association of cathepsin B in human prostate cancer: biochemical and immunogold electron microscopic analysis[J]. Prostate, 2001, 49 (3): 172- 184.
3 MAHMOOD U , TUNG C H , BOGDANOV A JR , et al. Near-infrared optical imaging of protease activity for tumor detection[J]. Radiology, 1999, 213 (3): 866- 870.
4 HABIBOLLAHI P , FIGUEIREDO J , HEIDARI P , et al. Optical imaging with a Cathepsin B activated probe for the enhanced detection of esophageal adenocarcinoma by dual channel fluorescent upper GI endoscopy[J]. Theranostics, 2012, 2 (2): 227- 234.
5 RYAN L S , LIPPERT A R . Ultrasensitive chemiluminescent detection of cathepsin B: insights into the new frontier of chemiluminescent imaging[J]. Angew Chem Int Ed Engl, 2018, 57 (3): 622- 624.
6 TASSALI N , KOTERA N , BOUTIN C , et al. Smart detection of toxic metal ions, Pb2+ and Cd2+, using a 129Xe NMR-based sensor[J]. Anal Chem, 2014, 86 (3): 1783- 1788.
7 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.
7 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.
8 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.
9 WALKER T , HAPPER W . Spin-exchange optical pumping of noble-gas nuclei[J]. Rev Mod Phys, 1997, 69 (2): 629- 642.
10 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.
11 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.
12 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.
12 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.
13 WANG Y F , DMOCHOWSKI I J . An expanded palette of xenon-129 NMR biosensors[J]. Acc Chem Res, 2016, 49 (10): 2179- 2187.
14 YUAN C L , GUO Q N , CHEN S Z , et al. A novel molecular cage for hyperpolarized 129Xe based on cucurbit [6] uril nanoparticles[J]. Chinese J Magn Reson, 2019, 36 (4): 472- 480.
14 袁晨露, 郭茜旎, 陈世桢, 等. 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.
15 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.
16 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.
17 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.
18 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.
19 ZENG Q B , GUO Q N , YUAN Y P , et al. Mitochondria targeted and intracellular biothiol triggered hyperpolarized 129Xe magnetofluorescent biosensor[J]. Anal Chem, 2017, 89 (4): 2288- 2295.
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]. Chemistry, 2010, 16 (43): 41- 46.
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 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.
23 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.
24 YANG S J , YUAN Y P , JIANG W P , et al. Hyperpolarized Xe-129 magnetic resonance imaging sensor for H2S[J]. Chemistry-A European Journal, 2017, 23 (32): 7648- 7652.
25 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.
26 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.
27 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.
28 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.
29 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.
30 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.
31 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.
32 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.
33 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.
34 BROKER L E , HUISMAN C , SPAN S W , et al. Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells[J]. Cancer Research, 2004, 64, 27- 30.
Outlines

/