Quantitative profiling of integrin αvβ3 on single cells with quantum dot labeling to reveal the phenotypic heterogeneity of glioblastoma

Wang, Tingting; Li, Guang; Wang, Dianbing; Li, Feng; Men, Dong; Hu, Tao; Yan, Xin; Zhang, Xian-En

doi:10.1039/c9nr01105f

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…It is publicly acknowledged that three-dimensional (3D)-SIM is potentially faster and more photon efficient than other SR techniques in increasing the spatial resolution, a QD-based probe is a useful tool for molecular profiling and U87MG has the highest expression level of integrin αvβ3 , heterodimeric cell-surface receptors, among glioma cell lines U87MG, U251, and LN229.…”

Section: Experimental Sectionmentioning

confidence: 99%

Calibration-Free Single-Molecule Absolute Quantification Using Super-resolution Microscopy

Zhang

2021

Anal. Chem.

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Single-molecule (SM) quantification has become a powerful analytical technique in the fields of physics, chemistry, and biology. SM imaging, especially with super-resolution (SR) techniques, has dramatically facilitated the study of individual molecules that may function as disease-related biomarkers. Although multiple properties can be used for quantitative imaging analysis, counting may be the simplest and most direct way. Consequently, how to utilize the greater spatial resolution to overcome undercounting or overcounting errors in certain conditions shows promising potential to unravel intracellular mechanisms of isolated biomolecules. From this perspective, we present an absolute quantification approach, termed crucial connected-component entropy (CCCE), with subresolution accuracy for the SR SM detection platform without the need for prior knowledge of calibration, and a cross-validation analytical pipeline based on SM profiling for nanoscale performance assessments. Considering its high efficiency, accuracy, and robustness for routine SM quantification compared with commonly used strategies, we believe that this protocol will indubitably find wide applications in biochemistry research, drug discovery, and clinical diagnostics, especially molecular diagnostics.

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Section: Experimental Sectionmentioning

confidence: 99%

Calibration-Free Single-Molecule Absolute Quantification Using Super-resolution Microscopy

Zhang

2021

Anal. Chem.

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“…Gold nanoparticles targeted to integrin αvβ3 inhibited the integrin-dependent melanoma tumor cell adhesion to vitronectin, with very low non-specific background binding, making them a highly selective diagnostic probe and therapy [ 37 ]. Recently, a study quantified the density of integrin αvβ3 on glioblastoma cells and found that the density of receptors dictated the cell response to inhibitor molecules [ 38 ]. Cell viability and invasion following the inhibitor treatment correlated with the density of the integrin receptor at the surface.…”

Section: Nanoscale Cell Surface Receptor Regulation For Bio-instructive Therapeutic Designmentioning

confidence: 99%

“…Newer techniques including instant two-photon SIM or light-sheet SIM are being reported, but they are yet to be applied specifically to study the cell–material interface. [ 38 , 126 – 129 ] Electron microscopy Scanning electron microscopy (SEM) and Focused ion beam (FIB)-SEM ✔ ✔ ✔ < 5 nm (XY), 50 nm (Z) - ✖ ✖ ✖ -Very time- and labor-intensive sample preparation. Can be subject to artifacts due to sample dehydration, processing, and staining.…”

Section: Nanoscale Imaging Of Cell Surface Receptor Organization and Cell–materials Interactionsmentioning

confidence: 99%

Advancing Cell-Instructive Biomaterials Through Increased Understanding of Cell Receptor Spacing and Material Surface Functionalization

Maynard

Winter

Cunnane

et al. 2020

Regen. Eng. Transl. Med.

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Regenerative medicine is aimed at restoring normal tissue function and can benefit from the application of tissue engineering and nano-therapeutics. In order for regenerative therapies to be effective, the spatiotemporal integration of tissue-engineered scaffolds by the native tissue, and the binding/release of therapeutic payloads by nano-materials, must be tightly controlled at the nanoscale in order to direct cell fate. However, due to a lack of insight regarding cell–material interactions at the nanoscale and subsequent downstream signaling, the clinical translation of regenerative therapies is limited due to poor material integration, rapid clearance, and complications such as graft-versus-host disease. This review paper is intended to outline our current understanding of cell–material interactions with the aim of highlighting potential areas for knowledge advancement or application in the field of regenerative medicine. This is achieved by reviewing the nanoscale organization of key cell surface receptors, the current techniques used to control the presentation of cell-interactive molecules on material surfaces, and the most advanced techniques for characterizing the interactions that occur between cell surface receptors and materials intended for use in regenerative medicine. Lay Summary The combination of biology, chemistry, materials science, and imaging technology affords exciting opportunities to better diagnose and treat a wide range of diseases. Recent advances in imaging technologies have enabled better understanding of the specific interactions that occur between human cells and their immediate surroundings in both health and disease. This biological understanding can be used to design smart therapies and tissue replacements that better mimic native tissue. Here, we discuss the advances in molecular biology and technologies that can be employed to functionalize materials and characterize their interaction with biological entities to facilitate the design of more sophisticated medical therapies.

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“…Nuclear medicine and molecular imaging are important for the quantitative evaluation of membrane receptors and biological tumour behaviour [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…Integrins are a diverse family of glycoproteins that form heterodimeric receptors for extracellular matrix molecules [15][16][17], of which integrin α v β 3 , with an exposed arginine-glycine-aspartate (RGD) tripeptide sequence, is the most-extensively studied [17]. Integrin α v β 3 is highly expressed in the neovasculature in solid tumours, including neuroblastoma, osteosarcoma, glioblastoma, breast cancer, and prostate cancer [10,[18][19][20][21][22][23][24][25]. The highly restricted expression of integrin α v β 3 in normal tissues compared with its overexpression in tumour cells suggests that it may provide an interesting molecular target for the early detection of malignant tumours [18].…”

Section: Introductionmentioning

confidence: 99%

99mTc-Galacto-RGD2 Integrin αvβ3 Targeted Imaging as a Surrogate for Molecular Phenotyping in Lung Cancer: Prospective Study in the Real World

Fu¹,

Yan²,

Fu³

et al. 2021

Preprint

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Purpose: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of 99mTc-Galacto-RGD2 single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, Integrin αvβ3 expression, and neovascularization in lung cancer subtypes was also addressed. Methods: A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prostective study from January 2013 to December 2016. All patients underwent 99mTc-Galacto-RGD2 imaging. The region of interest was drawn around each primary lesion, and tumour uptake of 99mTc-Galacto-RGD2 was measured as the tumour/normal tissue ratio（T/N）. The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour tissues were obtained from 66 patients with malignant diseases and seven with benign disease. Tumour expression levels of αvβ3, CD31, Ki-67, and CXCR4 were analysed to determine their value for phenotyping and metastasis potential evaluation. Results: The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of 99mTc-Galacto-RGD2 SPECT/CT using a cut-off value of 2.5 were 91.89 %, 48.0 %, and 86.67 %, respectively. Integrin αvβ3 expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αvβ3 expression. Integrin αvβ3 expression levels were significantly higher in advanced (Ⅲ, Ⅳ) than early stages (Ⅰ, Ⅱ). However, there was no significant correlation between tumour uptake and αvβ3 expression. Conclusion: 99mTc-Galacto-RGD2 SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer. RGD imaging may help evaluate the biological behaviour and phenotyping, and thus aid management in lung cancer.

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Quantitative profiling of integrin αvβ3 on single cells with quantum dot labeling to reveal the phenotypic heterogeneity of glioblastoma

Abstract: The distribution, localization and density of individual molecules (e.g. drug-specific receptors) on single cells can offer profound information about cell phenotypes.

Cited by 21 publications

References 33 publications

Calibration-Free Single-Molecule Absolute Quantification Using Super-resolution Microscopy

Calibration-Free Single-Molecule Absolute Quantification Using Super-resolution Microscopy

Advancing Cell-Instructive Biomaterials Through Increased Understanding of Cell Receptor Spacing and Material Surface Functionalization

99mTc-Galacto-RGD2 Integrin αvβ3 Targeted Imaging as a Surrogate for Molecular Phenotyping in Lung Cancer: Prospective Study in the Real World

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