Novel cationic biodegradable multiblock poly(ε-caprolactone urethane)s that contain gemini quaternary ammonium side groups on the hard segments were developed. To obtain these polyurethanes, a new L-lysine-derivatized diamine containing gemini quaternary ammonium side groups (GA8) was first synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectra (NMR), mass spectrometry (MS), and high-resolution mass spectra (HRMS). Then a series of gemini poly(ε-caprolactone urethane)s were designed and prepared using L-lysine ethyl ester diisocyanate (LDI), poly(ε-caprolactone) (PCL) diols, 1,4-butandiol (BDO), and GA8 and were terminated by methoxyl-poly(ethylene glycol) (m-PEG). The obtained polyurethanes were fully characterized by 1 H NMR, gel permeation chromatograph (GPC), differential scanning calorimetry (DSC), FTIR, and water contact angle (WCA) measurement. The gemini polyurethane shows a rapid rate of hydrolytic and enzymatic degradation, as demonstrated by weight loss and polarizing light microscopy (PLM) observations. In vitro cytotoxicity analysis suggests that both the polyurethanes and their degradation products do not show significant inhibition effect against fibroblasts. Our work provides a new way to synthesize nontoxic and amphiphilic multiblock polyurethanes with rapid degradation rate, and these new materials could be good candidates as biodegradable carriers for drug and gene delivery.
Unique self-assembly behavior of novel nontoxic gemini cationic biodegradable multiblock poly(3-caprolactone urethane)s which contain both gemini quaternary ammonium and PEG groups is firstly reported. The micellar size, size distributions, zeta potential, CMC and K v could be well-tailored for application in drug and gene delivery.
Human red blood cells (hRBCs) possess a unique biconcave structure with a highly deformable cell membrane and condensed cytosol hemoglobin for oxygen delivery. Inspired by hRBCs, novel deformable core‐shell particles are developed as perfluorocarbon‐based oxygen carriers (OCs), called “cDFCs” (concave‐shaped deformable PFC‐based OCs), using the Shirasu porous glass (SPG) membrane emulsification technique. cDFCs have a perfluorooctyl bromide core of high oxygen solubility and poly(lactide‐co‐caprolactone) shell, which is thin and highly deformable. They have an optical equivalent diameter of 7.9 ± 2.5 µm and a unique concave shape. Owing to their low Young's modulus (93 kPa) and their diameter and shape, they successfully pass through a 4.5‐µm‐gap silicon microchannel as a blood capillary model. Enhanced oxygen supply to multiple layered cells is demonstrated under hypoxic conditions, indicating their efficiency as OCs. cDFCs are new potential OCs in tissue engineering and blood substitution in the future.
Background
The battle against Helicobacter pylori (H. pylori) infections demands fast, reliable, and sensitive methods for pathogen identification (ID), antimicrobial susceptibility tests (ASTs) based on metabolic response, and genome-wide mutation profiling that reveals resistance mechanisms.
Methods
Here we introduce Clinical Antimicrobial Susceptibility Test Ramanometry for H. pylori (CAST-R-HP), and its validation with clinical samples. This method performs rapid ID, metabolism inhibition–based AST, and high-quality whole-genome sequencing for cells of targeted resistance phenotype, all at precisely 1-cell resolution and directly from biopsy samples.
Results
In CAST-R-HP, automated acquisition and machine learning of single-cell Raman spectra (SCRS) enable distinguishing individual H. pylori cells directly from a biopsy sample, with 98.5 ± 0.27% accuracy in ID. Moreover, by adding a 48- to72-h D2O feeding and drug exposure step prior to SCRS acquisition, CAST-R-HP reports AST for levofloxacin and clarithromycin with 100% accuracy, based on metabolic inhibition level. Furthermore, CAST-R-HP supports rapid sorting, low-bias DNA amplification, and full genome sequencing of single H. pylori cells with the SCRS defined, targeted drug-susceptibility phenotype, via Raman-activated gravity-driven cell encapsulation and sequencing. The genome-wide mutation map (maximum 99.70% coverage), at precisely 1-cell resolution, not only elucidates the drug-susceptibility phenotypes but also unveils their underlying molecular mechanisms.
Conclusion
The culture independency, shorter turnaround time, high resolution, and comprehensive information output suggest that CAST-R-HP is a powerful tool for diagnosing and treating H. pylori infections.
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