quantifyingtheadhesionforcesoflymphomacellsbyafmsinglecellforcespectroscopy

Cell adhesion plays an important role in regulating diverse physiological functions of cells, and quantitatively characterizing the adhesive behaviors at single-cell level benefits understanding the biology of cells. The advent of atomic force microscopy (AFM) provides a powerful method for investigating the biophysical properties of biological systems at micro/nanoscale under aqueous conditions, and particularly AFM-based single-cell force spectroscopy (SCFS) is able to measure the adhesion forces of single cells. Nevertheless, current SCFS assays are commonly performed on adherent cells, and SCFS studies on mammalian suspended cells are still scarce. In this work, AFM-based SCFS was utilized to measure the adhesion forces of lymphoma cells. First, the adhesion forces between lymphoma cells and rituximab (an antibody which binds to the CD20 antigen on lymphoma cells to activate immunotherapy) were investigated. Then the effects of antibody concentration and experimental parameters on the adhesion force measurements were investigated. Next, the intercellular adhesion forces between lymphoma cells were quantified. The research demonstrates the capabilities of AFM-based SCFS in detecting the adhesive behaviors of mammalian suspended cells and also provides novel insights into the adhesion of lymphoma cells, which will have potential impacts on single-cell biomechanical assays

Enteric Polymer Based on pH-Responsive Aliphatic Polycarbonate Functionalized with Vitamin E To Facilitate Oral Delivery of Tacrolimus

To improve the bioavailability of orally administered drugs, we synthesized a pH-sensitive polymer (poly­(ethylene glycol)–poly­(2-methyl-2-carboxyl-propylene carbonate)–vitamin E, mPEG–PCC–VE) attempting to integrate the advantages of enteric coating and P-glycoprotein (P-gp) inhibition. The aliphatic polycarbonate chain was functionalized with carboxyl groups and vitamin E via postpolymerization modification. Optimized by comparison and central composite design, mPEG₁₁₃–PCC₃₂–VE₄ exhibited low critical micelle concentration of 1.7 × 10^–6 mg/mL and high drug loading ability for tacrolimus (21.2% ± 2.7%, w/w). The pH-responsive profile was demonstrated by pH-dependent swelling and <i>in vitro</i> drug release. Less than 4.0% tacrolimus was released under simulated gastric fluid after 2.5 h, whereas an immediate release was observed under simulated intestinal fluid. The mPEG₁₁₃–PCC₃₂–VE₄ micelles significantly increased the absorption of P-gp substrate tacrolimus in the whole intestine. The oral bioavailability of tacrolimus micelles was 6-fold higher than that of tacrolimus solution in rats. This enteric polymer therefore has the potential to become a useful nanoscale carrier for oral delivery of drugs