scholarly journals Near-Infrared Fluorescent Agent for In Vitro Screening of Endometrial Cancer and Precancerous Lesions

2021 ◽  
Vol 11 ◽  
Author(s):  
Dongxin Liang ◽  
Xiaoqian Tuo ◽  
Qing Wang ◽  
Lanbo Zhao ◽  
Kailu Zhang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Folic Acid ◽  
Predictive Value ◽  
Near Infrared ◽  
Diagnostic Utility ◽  
H Nmr ◽  
Ultraviolet Spectra ◽  
Precancerous Change ◽  
Fluorescent Agent

The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.

scholarly journals A Targeted Folate Receptor-α Near-infrared Fluorescent Agent Used for in Vitro Diagnosis of Endometrial Cytology

2020 ◽  
Author(s):  
Dongxin Liang ◽  
Xiaoqian Tuo ◽  
Lanbo Zhao ◽  
Kailu Zhang ◽  
Yiran Wang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Efficient Method ◽  
Predictive Value ◽  
Near Infrared ◽  
Folate Receptor ◽  
Intraoperative Imaging ◽  
False Negative ◽  
Endometrial Cytology ◽  
In Vitro Diagnosis

Abstract Background Endometrial cancer is the second-most prevalent cancer after breast cancer. Endometrial cytology test is a new diagnosis method for endometrial lesions. However, some unresolved issues limited the application of endometrial cytology test (ECT) in early diagnosis and screening of endometrial cancer. Evidence suggests that FRα is overexpressed in various solid tumors such as endometrial cancer, breast carcinoma, ovarian cancer and so on. Based on the expression of FR-α, the agent used in intraoperative imaging, FRα-targeting antibody drugs and diagnosis were developed previously. Nevertheless, research regarding agents used in the diagnosis of endometrial cancer is rarely carried out yet. Methods To obtain a promising and efficient method for in vitro and screening diagnosis of endometrial cytology, we performed the synthesis and evaluation of the new near-infrared targeting fluorescent dye folic acid-ZW800-1 (ZW-FA) and to explore its potential feasibility for in vitro diagnosis of endometrial cancer. Characterisation and Folate receptor-α (FR-α) targeting verification of ZW-FA were performed first and 92 patients were recruited, after liquid-based cytology preparations, during a 15-month period. ZW-FA and Hematoxylin-Eosin (H&E) staining were performed on all cytological slides successively; the histological diagnoses were regarded as the gold standard for ROC curve analysis. Results The cut-off value of ZW-FA fluorescence intensity is 62.9745; the sensitivity (Se), specificity (Sp), false-negative rate (FNR), false-positive rate (FPR), positive predictive value (PV+) percentage and negative predictive value (PV–) of the ZW-FA method are 84.6%, 85.2%, 15.4%,14.8%, 93.2% and 69.7%, respectively. Conclusions ZW-FA is potentially efficient for in vitro diagnosis of endometrial lesions based on the FR-α expression level of different endometrial lesions. This research offers a promising and efficient method for in vitro and screening diagnosis of endometrial cytology. Trial registration: ChiCTR1800020123. Registered December 15, 2018.

scholarly journals A targeted folate receptor-α near-infrared fluorescent agent used for in vitro diagnosis of endometrial cytology

2020 ◽  
Author(s):  
Dongxin Liang ◽  
Xiaoqian Tuo ◽  
Lanbo Zhao ◽  
Kailu Zhang ◽  
Yiran Wang ◽  
...  
Keyword(s):  
Predictive Value ◽  
Near Infrared ◽  
Folate Receptor ◽  
False Positive Rate ◽  
False Negative ◽  
False Negative Rate ◽  
Roc Curve Analysis ◽  
Fluorescent Agent ◽  
In Vitro Diagnosis

AbstractThe aim of this study is to perform the synthesis and evaluation of the new near-infrared targeting fluorescent dye folic acid-ZW800-1 (ZW-FA) and to explore its potential feasibility for in vitro diagnosis of endometrial cancer. Characterisation and Folate receptor-α (FR-α) targeting verification of ZW-FA were performed first and 92 patients were recruited, after liquid-based cytology preparations, during a 15-month period. ZW-FA and Hematoxylin-Eosin (H&E) staining were performed on all cytological slides successively; the histological diagnoses were regarded as the gold standard for ROC curve analysis. The cut-off value of ZW-FA fluorescence intensity is 62.9745; the sensitivity (Se), specificity (Sp), false-negative rate (FNR), false-positive rate (FPR), positive predictive value (PV+) percentage and negative predictive value (PV–) of the ZW-FA method are 84.6%, 85.2%, 15.4%,14.8%, 93.2% and 69.7%, respectively. ZW-FA is potentially efficient for in vitro diagnosis of endometrial lesions based on the FR-α expression level of different endometrial lesions.

Folic Acid Functionalized Chlorin e6-Superparamagnetic Iron Oxide Nanocarriers as a Theranostic Agent for MRI-Guided Photodynamic Therapy

2021 ◽  
Vol 17 (2) ◽  
pp. 205-215
Author(s):  
Zhenbo Sun ◽  
Mingfang Luo ◽  
Jia Li ◽  
Ailing Wang ◽  
Xucheng Sun ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Folic Acid ◽  
Iron Oxide ◽  
Near Infrared ◽  
Biological Fluids ◽  
Superparamagnetic Iron Oxide ◽  
Chlorin E6 ◽  
Theranostic Agent

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.

scholarly journals PEGylated-folic acid–modified black phosphorus quantum dots as near-infrared agents for dual-modality imaging-guided selective cancer cell destruction

Nanophotonics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 2425-2435 ◽  
Author(s):  
Jing Wang ◽  
Dong Liang ◽  
Zehua Qu ◽  
Ivan M. Kislyakov ◽  
Valery M. Kiselev ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Folic Acid ◽  
Cancer Cells ◽  
Near Infrared ◽  
Processing System ◽  
Black Phosphorus ◽  
Optical Absorbance ◽  
Present Design ◽  
Black Phosphorus Quantum Dots

AbstractBiological systems have high transparence to 700–1100-nm near-infrared (NIR) light. Black phosphorus quantum dots (BPQDs) have high optical absorbance in this spectrum. This optical property of BPQDs integrates both diagnostic and therapeutic functions together in an all-in-one processing system in cancer theranostic approaches. In the present study, BPQDs were synthesized and functionalized by targeting moieties (PEG-NH2-FA) and were further loaded with anticancer drugs (doxorubicin) for photodynamic–photothermal–chemotherapy. The precise killing of cancer cells was achieved by linking BPQDs with folate moiety (folic acid), internalizing BPQDs inside cancer cells with folate receptors and NIR triggering, without affecting the receptor-free cells. These in vitro experiments confirm that the agent exhibited an efficient photokilling effect and a light-triggered and heat-induced drug delivery at the precise tumor sites. Furthermore, the nanoplatform has good biocompatibility and effectively obliterates tumors in nude mice, showing no noticeable damages to noncancer tissues. Importantly, this nanoplatform can inhibit tumor growth through visualized synergistic treatment and photoacoustic and photothermal imaging. The present design of versatile nanoplatforms can allow for the adjustment of nanoplatforms for good treatment efficacy and multiplexed imaging, providing an innovation for targeted tumor treatment.

scholarly journals Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo

2015 ◽  
Vol 27 (2) ◽  
pp. 427-438 ◽  
Author(s):  
Allison S. Cohen ◽  
Renata Patek ◽  
Steven A. Enkemann ◽  
Joseph O. Johnson ◽  
Tingan Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Opioid Receptor ◽  
Near Infrared ◽  
Delta Opioid Receptor ◽  
Fluorescent Agent

scholarly journals 880 nm NIR-Triggered Organic Small Molecular-Based Nanoparticles for Photothermal Therapy of Tumor

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 773
Author(s):  
Yunying Zhao ◽  
Zheng He ◽  
Qiang Zhang ◽  
Jing Wang ◽  
Wenying Jia ◽  
...  
Keyword(s):  
Folic Acid ◽  
Polyethylene Glycol ◽  
Tumor Microenvironment ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Selective Treatment ◽  
Deep Tissue ◽  
Constant Attention ◽  
Nir Laser

Photothermal therapy (PTT) has received constant attention as an efficient cancer therapy method due to locally selective treatment, which is not affected by the tumor microenvironment. In this study, a novel 880 nm near-infrared (NIR) laser-triggered photothermal agent (PTA), 3TT-IC-4Cl, was used for PTT of a tumor in deep tissue. Folic acid (FA) conjugated amphiphilic block copolymer (folic acid-polyethylene glycol-poly (β-benzyl-L-aspartate)10, FA-PEG-PBLA10) was employed to encapsulate 3TT-IC-4Cl by nano-precipitation to form stable nanoparticles (TNPs), and TNPs exhibit excellent photothermal stability and photothermal conversion efficiency. Furthermore, the in vitro results showed TNPs display excellent biocompatibility and significant phototoxicity. These results suggest that 880 nm triggered TNPs have great potential as effective PTAs for photothermal therapy of tumors in deep tissue.

scholarly journals Use in vitro of Gold Nanoparticles Functionalized with Folic Acid as a Photothermal Agent on Treatment of HeLa Cells

2018 ◽  
Vol 62 (1) ◽  
Author(s):  
Linda Bertel Garay ◽  
Fernando Martínez Ortega ◽  
Stelia Carolina Méndez-Sanchez
Keyword(s):  
Gold Nanoparticles ◽  
Folic Acid ◽  
Cancer Cells ◽  
Hela Cells ◽  
Near Infrared ◽  
Infrared Light ◽  
Molar Ratio ◽  
Functionalized Gold Nanoparticles ◽  
Dose Dependent

<p>Folic acid (FA) is used as a recognition molecule to achieve selective internalization in cancer cells. Here functionalized gold nanoparticles with folic acid (AuNP-FA) are proposed as suitable therapeutic agents for cervix cancer cells by photothermal damage. The functionalized gold nanoparticles with folic acid were synthesized by mixing hydrogen tetrachloroaurate with folic acid in a molar ratio of 0.56/1 under radiation of mercury lamp (λ<sub>max</sub>=254 nm). HeLa cells were incubated with AuNP-FA during 48 h, then were irradiated and the cytotoxicity was analyzed 12 h after irradiation. The AuNP-FA were dose-dependent cytotoxic under irradiation and not cytotoxic in the absence of radiation. The viability of cancer cells treated with functionalized and non-functionalized gold nanoparticles (AuNPs), with and without near infrared light at 808 nm, was measured by MTT assays. This work provides useful guidance toward the synthesis of biocompatible nanomaterials for biological applications.</p>

scholarly journals NIR Photosensitizer for Two-Photon Fluorescent Imaging and Photodynamic Therapy of Tumor

2021 ◽  
Vol 9 ◽  
Author(s):  
Lujia Chen ◽  
Meijuan Chen ◽  
Yuping Zhou ◽  
Changsheng Ye ◽  
Ruiyuan Liu
Keyword(s):  
Photodynamic Therapy ◽  
Near Infrared ◽  
Fluorescent Imaging ◽  
Deep Tissue ◽  
Two Photon ◽  
Nir Emission ◽  
Good Biocompatibility ◽  
Fluorescent Agent

Preparation of near-infrared (NIR) emissive fluorophore for imaging-guided PDT (photodynamic therapy) has attracted enormous attention. Hence, NIR photosensitizers of two-photon (TP) fluorescent imaging and photodynamic therapy are highly desirable. In this contribution, a novel D-π-A structured NIR photosensitizer (TTRE) is synthesized. TTRE demonstrates near-infrared (NIR) emission, good biocompatibility, and superior photostability, which can act as TP fluorescent agent for clear visualization of cells and vascular in tissue with deep-tissue penetration. The PDT efficacy of TTRE as photosensitizer is exploited in vitro and in vivo. All these results confirm that TTRE would serve as potential platform for TP fluorescence imaging and imaging-guided photodynamic therapy.

scholarly journals Targeted Nanoparticles for Fluorescence Imaging of Folate Receptor Positive Tumors

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1651
Author(s):  
Aimee J. Marko ◽  
Ballav M. Borah ◽  
Kevin E. Siters ◽  
Joseph R. Missert ◽  
Anurag Gupta ◽  
...  
Keyword(s):  
Folic Acid ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Folate Receptor ◽  
Cyanine Dye ◽  
Target Specificity ◽  
Nir Fluorescence ◽  
Positive Breast Cancer

This report presents the synthesis and folate receptor target-specificity of amino-functionalized polyacrylamide nanoparticles (AFPAA NPs) for near-infrared (NIR) fluorescence imaging of cancer. For the synthesis of desired nano-constructs, the AFPAA NPs (hereafter referred to as NPs) were reacted with a NIR cyanine dye (CD) bearing carboxylic acid functionality by following our previously reported approach, and the resulting conjugate (NP-CD) on further reaction with folic acid (FA) resulted in a new nano-construct, FA-NP-CD, which demonstrated significantly higher uptake in folate receptor-positive breast cancer cells (KB+) and in folate receptor over-expressed tumors in vivo. The target-specificity of these nanoparticles was further confirmed by inhibition assay in folate receptor-positive (KB+) and -negative (HT-1080) cell lines. To show the advantages of polyacrylamide (PAA)-based NPs in folate receptor target-specificity, the CD used in preparing the FA-NP-CD construct was also reacted with folic acid alone and the synthetic conjugate (CD-FA) was also investigated for its target-specificity. Interestingly, in contrast to NPs (FA-NP-CD), the CD-FA conjugate did not show any significant in vitro or in vivo specificity toward folate receptors, showing the advantages of PAA-based nanotechnology in delivering the desired agent to tumor cells.

Tissue plasminogen activator as a novel diagnostic aid in acute pulmonary embolism

VASA ◽  
2014 ◽  
Vol 43 (6) ◽  
pp. 450-458 ◽  
Author(s):  
Julio Flores ◽  
Ángel García-Avello ◽  
Esther Alonso ◽  
Antonio Ruíz ◽  
Olga Navarrete ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Negative Predictive Value ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Predictive Value ◽  
Acute Pulmonary Embolism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diagnostic Utility ◽  
Tissue Plasminogen ◽  
D Dimer

Background: We evaluated the diagnostic efficacy of tissue plasminogen activator (tPA), using an enzyme-linked immunosorbent assay (ELISA) and compared it with an ELISA D-dimer (VIDAS D-dimer) in acute pulmonary embolism (PE). Patients and methods: We studied 127 consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on a clinical probability pretest for PE and a strict protocol of imaging studies. A plasma sample to measure the levels of tPA and D-dimer was obtained at enrollment. Diagnostic accuracy for tPA and D-dimer was determined by the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity, predictive values, and the diagnostic utility of tPA with a cutoff of 8.5 ng/mL and D-dimer with a cutoff of 500 ng/mL, were calculated for PE diagnosis. Results: PE was confirmed in 41 patients (32 %). Areas under ROC curves were 0.86 for D-dimer and 0.71 for tPA. The sensitivity/negative predictive value for D-dimer using a cutoff of 500 ng/mL, and tPA using a cutoff of 8.5 ng/mL, were 95 % (95 % CI, 88–100 %)/95 % (95 % CI, 88–100 %) and 95 % (95 % CI, 88–100 %)/94 %), respectively. The diagnostic utility to exclude PE was 28.3 % (95 % CI, 21–37 %) for D-dimer and 24.4 % (95 % CI, 17–33 %) for tPA. Conclusions: The tPA with a cutoff of 8.5 ng/mL has a high sensitivity and negative predictive value for exclusion of PE, similar to those observed for the VIDAS D-dimer with a cutoff of 500 ng/mL, although the diagnostic utility was slightly higher for the D-dimer.

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