Detection of breast cancer cells using targeted magnetic nanoparticles and ultra-sensitive magnetic field sensors

Introduction

Breast cancer detection using mammography has improved clinical outcomes for many women, because mammography can detect very small (5 mm) tumors early in the course of the disease. However, mammography fails to detect 10 - 25% of tumors, and the results do not distinguish benign and malignant tumors. Reducing the false positive rate, even by a modest 10%, while improving the sensitivity, will lead to improved screening, and is a desirable and attainable goal. The emerging application of magnetic relaxometry, in particular using superconducting quantum interference device (SQUID) sensors, is fast and potentially more specific than mammography because it is designed to detect tumor-targeted iron oxide magnetic nanoparticles. Furthermore, magnetic relaxometry is theoretically more specific than MRI detection, because only target-bound nanoparticles are detected. Our group is developing antibody-conjugated magnetic nanoparticles targeted to breast cancer cells that can be detected using magnetic relaxometry.

Methods

To accomplish this, we identified a series of breast cancer cell lines expressing varying levels of the plasma membrane-expressed human epidermal growth factor-like receptor 2 (Her2) by flow cytometry. Anti-Her2 antibody was then conjugated to superparamagnetic iron oxide nanoparticles using the carbodiimide method. Labeled nanoparticles were incubated with breast cancer cell lines and visualized by confocal microscopy, Prussian blue histochemistry, and magnetic relaxometry.

Results

We demonstrated a time- and antigen concentration-dependent increase in the number of antibody-conjugated nanoparticles bound to cells. Next, anti Her2-conjugated nanoparticles injected into highly Her2-expressing tumor xenograft explants yielded a significantly higher SQUID relaxometry signal relative to unconjugated nanoparticles. Finally, labeled cells introduced into breast phantoms were measured by magnetic relaxometry, and as few as 1 million labeled cells were detected at a distance of 4.5 cm using our early prototype system.

Conclusions

These results suggest that the antibody-conjugated magnetic nanoparticles are promising reagents to apply to in vivo breast tumor cell detection, and that SQUID-detected magnetic relaxometry is a viable, rapid, and highly sensitive method for in vitro nanoparticle development and eventual in vivo tumor detection.     

Utilization of Maternal Health Care Among Immigrant Mothers in New York City, 2016–2018

Immigrant women represent half of New York City (NYC) births, and some immigrant groups have elevated risk for poor maternal health outcomes. Disparities in health care utilization across the maternity care spectrum may contribute to differential maternal health outcomes. Data on immigrant maternal health utilization are under-explored in the literature. We conducted a cross-sectional analysis of the population-based NYC Pregnancy Risk Assessment Monitoring System survey, using 2016–2018 data linked to birth certificate variables, to explore self-reported utilization of preconception, prenatal, and postpartum health care and potential explanatory pathways. We stratified results by maternal nativity and, for immigrants, by years living in the US; geographic region of origin; and country of origin income grouping. Among immigrant women, 43% did not visit a health care provider in the year before pregnancy, compared to 27% of US-born women (risk difference [RD] = 0.16, 95% CI [0.13, 0.20]), 64% had no dental cleaning during pregnancy compared to 49% of US-born women (RD = 0.15, 95% CI [0.11, 0.18]), and 11% lost health insurance postpartum compared to 1% of US-born women (RD = 0.10, 95% CI [0.08, 0.11]). The largest disparities were among recent arrivals to the US and immigrants from countries in Central America, South America, South Asia, and sub-Saharan Africa. Utilization differences were partially explained by insurance type, paternal nativity, maternal education, and race and ethnicity. Disparities may be reduced by collaborating with community-based organizations in immigrant communities on strategies to improve utilization and by expanding health care access and eligibility for public health insurance coverage before and after pregnancy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11524-021-00584-5.     

Characterization of a new curtovirus,pepper yellow dwarf virus,from chile pepper and distribution in weed hosts in New Mexico

Over 4,950 asymptomatic weed samples from more than 20 weed species that are host plants for curtoviruses were collected from ten chile pepper fields in southern New Mexico (NM) during 2003, 2004 and 2005 to identify whether they were infected with curtoviruses and to determine which curtoviruses were distributed in the weed population. Polymerase chain reaction using primers designed to detect a portion of the coat protein (cp) gene were used to detect curtoviruses, and infected plants were further tested for specific curtoviruses using primers designed to detect to a portion of the replication-associated protein (rep) gene. Amplification of the cp gene was successful from 3.7, 1.17, and 1.9% of the weed samples in 2003, 2004, and 2005, respectively. Seventy-three amplicons from those samples were sequenced and compared to well-characterized curtoviruses. Analysis of the rep nucleotide sequences showed that ~32.9% of the weed isolates tested were closely related to beet mild curly top virus (BMCTV). Approximately 12.4% were closely related to beet severe curly top virus (BSCTV). The rest of the weed isolates (54.7%), which shared a very high level of nucleotide sequence identity to each other, represent a new curtovirus species. Using eight primers designed for PCR, complete genomes of three curtoviruses isolated from chile pepper samples representing the three groups of curtoviruses in southern New Mexico were sequenced. Comparisons of whole sequences of the genomes revealed that the DG2SW171601 isolate (2,929 nucleotides) was nearly identical to BMCTV-W4 (~98% nucleotide sequence identity). The LRME27601 isolate (2,927 nucleotides) was most closely related to BSCTV (~92% nucleotide sequence identity). The LJN17601 isolate (2,959 nucleotides) shared only from 49.9 to 88.8% nucleotide sequence identity with other well-characterized curtoviruses. Based on the accepted cut-off of 89%, we propose that the LJN17601 isolate is a member of a new curtovirus species. Chile peppers infected with this virus in the field express chlorotic stunting symptoms, so we propose the name pepper yellow dwarf virus (PeYDV). This new curtovirus species may be the result of mutations in the genome and recombination between BMCTV-W4 and BSCTV.