Tuning Surface Plasmon Resonance Responses through Size and Crosslinking Control of Multivalent Protein Binding-Capable Nanoscale Hydrogels.

Surface plasmon resonance (SPR) phenomena have been widely studied to detect biomolecules because of their high sensitivity and ability to determine biomolecular interactions with kinetic information. However, highly selective detection in specific concentration ranges relevant to target biomolecules is still a challenging task. Recently, we developed bioresponsive nanoscale hydrogels to selectively intensify SPR signals through multivalent protein binding (MPB) events with target biomolecules, including IL-2, where we were able to demonstrate exceptional selectivity for target biomolecules with minimal responses to nonspecific and monovalent binding events. In this work, we systematically explored the relationship between the physical properties of MPB-capable nanoscale hydrogels and their SPR response induced in the presence of the programmed cell death protein 1 antibody (PD-1Ab) as a model target biomolecule. First, we developed a synthetic protocol by controlling various reaction parameters to construct a library of nanoscale poly(N-isopropylacrylamide-co-acrylic acid) hydrogels (NHs) with different sizes (from 400 nm to 1 µm) and degrees of crosslinking (from 2 to 8%). Then, by incorporating MPB-capable PD-1 receptors onto the surface of NHs to form PD-1-responsive nanoscale hydrogels (PNHs), the hydrogel size and crosslinking dependency of their SPR responses were investigated. Our results reveal the appropriate hydrogel size regime and degree of crosslinking for effective PD-1Ab detection at specific concentrations range between a few nM and 1 µM. Overall, our study demonstrates that by tuning the physical properties of the nanoscale hydrogel matrix, the sensitivity and detection range of MPB-based SPR sensors can be modulated to potentially benefit clinical applications such as monitoring diverse therapeutic biomolecules.

Simple Host-Guest Assembly for High-Resolution Magnetic Resonance Imaging of Microvasculature.

Magnetic resonance angiography (MRA) is an important imaging technique that can be used to identify and characterize various types of vascular diseases. However, currently used molecular contrast agents are unsuitable for MRA due to the short intravascular retention time, the whole-body distribution, and the relatively low contrast effect. In this study, we developed a vascular analysis contrast agent (i.e., VasCA) for MRA, which is a simple and biocompatible 1:1 host-guest assembly of PEGylated ß-cyclodextrin and gadolinium chelate with renal clearable size and high relaxivity (r1 = 9.27 mM-1 s-1). Its biocompatibility was confirmed by in vivo animal studies as well as in vitro 3D cell culture. In a tumor-bearing rat model, VasCA circulated in the blood vessels much longer (4.3-fold increase) than gadoterate meglumine (Dotarem) and was mainly excreted by the renal system after intravenous injection. This feature of VasCA allows characterization of tumor microvasculature (e.g., feeding and draining vessels) as well as visualization of small vessels in the brain and body organs. Furthermore, after treatment with an angiogenesis inhibitor (i.e., sorafenib), VasCA revealed the vessel normalization process and allowed the assessment of viable and necrotic tumor regions. Our study provides a useful tool for diverse MRA applications, including tumor characterization, early-stage evaluation of drug efficacy, and treatment planning, as well as diagnosis of cardiovascular diseases.

Relationship between Age at Menarche and Metabolic Syndrome in Premenopausal Women: Korea National Health and Nutrition Examination Survey 2013-2014.

BACKGROUND: Early menarche may be associated with increased risk of cardiovascular disease. The aim of this study was to evaluate the relationship between age at menarche and metabolic syndrome (MetS) in Korean premenopausal women. METHODS: We used nationally representative data from the Korea National Health and Nutrition Examination Survey from 2013 to 2014, and 3,023 premenopausal women aged 20-55 years were our subjects. We defined early menarche as age at first menstrual period less than 12 years. Multivariable logistic regression analysis was used to evaluate the relationship between age at menarche and MetS after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables. RESULTS: MetS was much more common in women aged 40-55 years than in women aged 20-39 years (4.1% vs. 15.1%). Compared with women who experienced menarche at age 12-15 years, the risk of MetS in the early menarche group was not higher in either age group, after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables (odds ratio [OR], 1.767; 95% confidence interval [CI], 0.718-4.351 in those aged 20-39 years; OR, 1.780; 95% CI, 0.775-4.085 in those aged 40-55 years). The risk of MetS in women with menarche at age ≥16 years was not higher than in women with menarche at age 12-15 years. CONCLUSION: Early or late menarche was not associated with an increased risk of MetS in premenopausal Korean women. Even before menopause, current age has a major influence on the development of MetS.