title: Quantitative Monitoring of Hypoxia-Induced Intracellular Acidification in Lung Tumor Cells and Tissues Using Activatable Surface-Enhanced Raman Scattering Nanoprobes.
abstract: Hypoxia is considered to contribute to pathophysiology in various cells and tissues, and a clear understanding about the relationship between hypoxia and intracellular acidification will help to elucidate the complex mechanism of glycolysis under hypoxia. However, current studies are mainly focused on overexpression of intracellular reductases accelerated by hypoxia, and the investigations focusing on the relationship between hypoxic degree and intracellular acidification remain to be explored. For this vacuity, we report herein a new activatable nanoprobe for sensing pH change under different degrees of hypoxia by surface-enhanced Raman spectroscopy (SERS). The monitoring was based on the SERS spectra changes of 4-nitrothiophenol (4-NTP)-functionalized gold nanorods (AuNR@4-NTP) resulting from the nitroreductase (NTR)-triggered reduction under hypoxic conditions while the as-generated 4-aminothiophenol (4-ATP) is a pH-sensitive molecule. This unique property can ensure the SERS monitoring of intracellular acidification in living cells and tissues under hypoxic conditions. Dynamic pH analysis indicated that the pH decreased from 7.1 to 6.5 as a function of different degrees of hypoxia (from 15 to 1%) due to excessive glycolytic activity triggered by hypoxia. Given the known advantages of SERS sensing, these findings hold promise in studies of pathophysiological pathways involving hypoxia.
authors: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, China.
authors: Dandan
authors: D
authors: Ma
authors: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, China.
authors: Jing
authors: J
authors: Zheng
authors: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, China.
authors: Pinting
authors: P
authors: Tang
authors: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, China.
authors: Weijian
authors: W
authors: Xu
authors: School of Chemistry and Biological Engineering, Changsha University of Science and Technology , Changsha, Hunan 410004, China.
authors: Zhihe
authors: Z
authors: Qing
authors: School of Chemistry and Biological Engineering, Changsha University of Science and Technology , Changsha, Hunan 410004, China.
authors: Sheng
authors: S
authors: Yang
authors: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, China.
authors: Jishan
authors: J
authors: Li
authors: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, China.|School of Chemistry and Biological Engineering, Changsha University of Science and Technology , Changsha, Hunan 410004, China.
authors: Ronghua
authors: R
authors: Yang
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D015394:Molecular Structure; D009601:Nitroreductases / Q000737:chemistry / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties
chemical_list: D013438:Sulfhydryl Compounds; C014712:4-nitrothiophenolate; D006046:Gold; D009601:Nitroreductases