scholarly journals A Novel Approach of Targeted Immunotherapy against Adenocarcinoma Cells with Nanoparticles Modified by CD16 and MUC1 Aptamers

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lianyuan Yu ◽  
Yan Hu ◽  
Jinhong Duan ◽  
Xian-Da Yang

Mucin 1 (MUC1) is a potentially important target of cancer therapy, being a glycoprotein that is overexpressed on cell surface of many types of adenocarcinomas, including breast, ovarian, colon, lung, and prostatic cancers. Several MUC1-targeted drug delivery systems have been developed and reported, but mobilizing natural killer cells (NK) to fight against MUC1-positive tumor has not been attempted. In this study, we introduced a novel amphipathic nanoparticle (NP) for enhancing the NK cytotoxicity to MUC1-positive cancer cells. The amphipathic NP had CD16 and MUC1 aptamers on its surface and was designed to bind with both the CD16-positive NK cells and the MUC1-positive tumor cells and pull the two types of cells close to each other. The fabricated amphipathic NP had an average size of 574 nm. The aptamers’ conjugation with the NP was confirmed by DNA hybridization experiments. Dark-field microscopy revealed that the amphipathic NP could recruit more NK cells to the vicinity of MUC1-positive cancer cells. Additionally, the amphipathic NP significantly enhanced the NK cytotoxicity to MUC1-positive cancer cellsp<0.01, but not that to the MUC1-negative control cells. The results suggest that NK cells may potentially be mobilized to selectively fight against MUC1-positive cancer cells.

Sensors ◽  
2019 ◽  
Vol 19 (21) ◽  
pp. 4652
Author(s):  
Rita La Spina ◽  
Diana C. António ◽  
Cloe Desmet ◽  
Andrea Valsesia ◽  
Radoslaw Bombera ◽  
...  

Development of sensitive methods for the determination of E. coli bacteria contamination in water distribution systems is of paramount importance to ensure the microbial safety of drinking water. This work presents a new sensing platform enabling the fast detection of bacteria in field samples by using specific antibodies as the biorecognition element and dark field microscopy as the detection technique. The development of the sensing platform was performed using non-pathogenic bacteria, with the E. coli DH5α strain as the target, and Bacillus sp. 9727 as the negative control. The identification of the captured bacteria was made by analyzing the dark field microscopy images and screening the detected objects by using object circularity and size parameters. Specificity tests revealed the low unspecific attachment of either E. coli over human serum albumin antibodies (negative control for antibody specificity) and of Bacillus sp. over E. coli antibodies. The system performance was tested using field samples, collected from a wastewater treatment plant, and compared with two quantification techniques (i.e., Colilert-18 test and quantitative polymerase chain reaction (qPCR)). The results showed comparable quantification capability. Nevertheless, the present method has the advantage of being faster, is easily adaptable to in-field analysis, and can potentially be extended to the detection of other bacterial strains.


2017 ◽  
Vol 53 (97) ◽  
pp. 13047-13050 ◽  
Author(s):  
Meng Li Liu ◽  
Hong Yan Zou ◽  
Chun Mei Li ◽  
Rong Sheng Li ◽  
Cheng Zhi Huang

Selenium nanoparticles with good water solubility and excellent biocompatibility are used for the first time as a light-scattering nanoprobe with aptamer modification to image nucleolin-overexpressing cancer cells through dark-field microscopy.


Author(s):  
J. Langmore ◽  
M. Isaacson ◽  
J. Wall ◽  
A. V. Crewe

High resolution dark field microscopy is becoming an important tool for the investigation of unstained and specifically stained biological molecules. Of primary consideration to the microscopist is the interpretation of image Intensities and the effects of radiation damage to the specimen. Ignoring inelastic scattering, the image intensity is directly related to the collected elastic scattering cross section, σɳ, which is the product of the total elastic cross section, σ and the eficiency of the microscope system at imaging these electrons, η. The number of potentially bond damaging events resulting from the beam exposure required to reduce the effect of quantum noise in the image to a given level is proportional to 1/η. We wish to compare η in three dark field systems.


Author(s):  
William Krakow

Tilted beam dark-field microscopy has been applied to atomic structure determination in perfect crystals, several synthesized molecules with heavy atcm markers and in the study of displaced atoms in crystals. Interpretation of this information in terms of atom positions and atom correlations is not straightforward. Therefore, calculated dark-field images can be an invaluable aid in image interpretation.


2019 ◽  
Vol 15 (2) ◽  
pp. 138-149
Author(s):  
Saleem Farooq ◽  
Javid A. Banday ◽  
Aashiq Hussain ◽  
Momina Nazir ◽  
Mushtaq A. Qurishi ◽  
...  

Background: Natural product, osthol has been found to have important biological and pharmacological roles particularly having inhibitory effect on multiple types of cancer. Objective: The unmet needs in cancer therapeutics make its derivatization an important and exciting field of research. Keeping this in view, a whole new series of diverse analogues of osthol (1) were synthesized. Method: All the newly synthesized compounds were made through modification in the lactone ring as well as in the side chain of the osthol molecule and were subjected to anti-proliferative screening through 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) against four different human cancers of diverse origins viz. Colon (Colo-205), lung (A549), Leukemia (THP- 1) and breast (MCF-7) including SV40 transformed normal breast epithelial cell (fR-2). Results: Interestingly, among the tested molecules, most of the analogs displayed better antiproliferative activity than the parent Osthol 1. However, among all the tested analogs, compound 28 exhibited the best results against leukemia (THP1) cell line with IC50 of 5µM.Compound 28 induced potent apoptotic effects and G1 phase arrest in leukemia cancer cells (THP1). The population of apoptotic cells increased from 13.8% in negative control to 26.9% at 8μM concentration of 28. Compound 28 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of the cancer cells. Conclusion: A novel series of molecules derived from natural product osthol were synthesized, wherein compound 28 was found to be most effective against leukemia and with 10 fold less toxicity against normal cells. The compound induced cancer inhibition mainly through apoptosis and thus has a potential in cancer therapeutics.


2020 ◽  
Vol 19 ◽  
pp. 153303382098328
Author(s):  
Zhen-Hua Du ◽  
Yu Xia ◽  
Qing Yang ◽  
Song Gao

Background and Objective: We have previously reported that BRCA2 N372 H i.a.1342A>C heterozygous variation presented in platinum-resistant patients. This study aimed to further investigate the mechanism of BRCA2 N372 H mutation in the development of platinum resistance in ovarian cancer. Methods: The BRCA2 N372 H i.a.1342A>C was synthesized and used to exchange 1 wildtype allele followed by sequencing to confirm the mutant allele sequence. Plasmids were constructed and transfected into the OVCAR-3 cells after lentiviral packaging. BRCA2 N372 H mRNA was detected by qPCR. BRCA2 protein was assessed by immunoblotting. Binding of the BRCA2 to Rad51 was detected by immunofluorescence staining. Sensitivity of the cells to cisplatin treatment was assessed with CCK-8 assay. Results: It was found that expression of BRCA2 protein in ovarian cancer cells transfected with BRCA2 N372 H i.a.1342A>C gene (2.177 ± 0.003) was significantly increased compared to that of the cells transfected with lenti-EGFP only (1.227 ± 0.003, P < 0.001). Binding of the BRCA2 and Rad51 proteins was significantly increased in the cells with BRCA2 N372 H i.a.1342A>C mutation (3.542 ± 0.24) than that in the cells transfected with lenti-EGFP (1.29 ± 0.32) or empty cells (1.363 ± 0.32, P < 0.001). Cell viability significantly increased in the cells transfected with BRCA2 N372 H mutant gene. The IC50 value was significantly higher in the cells transfected with BRCA2 N372 H mutant gene (1.963 ± 0.04) than that of the cells transfected with lenti-EGFP (0.955 ± 0.03, P < 0.01) or empty cells (1.043 ± 0.007, P < 0.01). Conclusion: Over expression of mRNA and protein of BRCA2 was detected in the cells with BRCA2 N372 H i.a.1342A>C mutation but not in the lentivirus negative control (lenti-EGFP) or the cells without transfection (empty cells), which may lead to resistance to platinum-based drugs in ovarian cancer cells through homologous recombination repair pathway.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3509
Author(s):  
Paule Marcoux-Valiquette ◽  
Cécile Darviot ◽  
Lu Wang ◽  
Andrée-Anne Grosset ◽  
Morteza Hasanzadeh Kafshgari ◽  
...  

Reliable cytopathological diagnosis requires new methods and approaches for the rapid and accurate determination of all cell types. This is especially important when the number of cells is limited, such as in the cytological samples of fine-needle biopsy. Immunoplasmonic-multiplexed- labeling may be one of the emerging solutions to such problems. However, to be accepted and used by the practicing pathologists, new methods must be compatible and complementary with existing cytopathology approaches where counterstaining is central to the correct interpretation of immunolabeling. In addition, the optical detection and imaging setup for immunoplasmonic-multiplexed-labeling must be implemented on the same cytopathological microscope, not interfere with standard H&E imaging, and operate as a second easy-to-use imaging method. In this article, we present multiplex imaging of four types of nanoplasmonic markers on two types of H&E-stained cytological specimens (formalin-fixed paraffin embedded and non-embedded adherent cancer cells) using a specially designed adapter for SI dark-field microscopy. The obtained results confirm the effectiveness of the proposed optical method for quantitative and multiplex identification of various plasmonic NPs, and the possibility of using immunoplasmonic-multiplexed-labeling for cytopathological diagnostics.


Nanoscale ◽  
2021 ◽  
Author(s):  
Paula Zamora-Perez ◽  
Beatriz Pelaz ◽  
Dionysia Tsoutsi ◽  
Mahmoud G. Soliman ◽  
Wolfgang J. Parak ◽  
...  

Hyperspectral-enhanced dark field microscopy to correlate Au/CuS NPs’ changes in their physicochemical properties induced by cellular environments with their functionality as photothermal probes by tracking their scattering profile evolution in real time.


Sign in / Sign up

Export Citation Format

Share Document