No abstract

This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier. Chitosan (CS), a natural polysaccharide largely obtained from marine crustaceans, is a promising drug delivery vector for therapeutics and diagnostics, owing to its biocompatibility, biodegradability, low toxicity, and structural variability. This review describes various approaches to obtain novel CS derivatives, including their distinct advantages, as well as different forms of nanomaterials recently developed from CS. The advanced applications of CS-based nanomaterials are presented here in terms of their specific functions. Recent studies have proven that nanotechnology combined with CS and its derivatives could potentially circumvent obstacles in the transport of drugs thereby improving the drug efficacy. CS-based nanomaterials have been shown to be highly effective in targeted drug therapy.

Technologies that can visualize, capture, and identify subsets of biomolecules that are not encoded by the genome in the context of healthy and diseased cells will offer unique opportunities to uncover the molecular mechanism of a multitude of physiological and disease processes. We describe here a chemical reporter strategy for labeling of cell surface glycoconjugates that takes advantage of recombinant glycosyltransferases and a corresponding sugar nucleotide functionalized by biotin. The exceptional efficiency of this method, termed one-step selective exoenzymatic labeling, or SEEL, greatly improved the ability to enrich and identify large numbers of tagged glycoproteins by LC–MS/MS. We further demonstrated that this labeling method resulted in far superior enrichment and detection of glycoproteins at the plasma membrane compared to a sulfo-NHS-activated biotinylation or two-step SEEL. This new methodology will make it possible to profile cell surface glycoproteomes with unprecedented sensitivity in the context of physiological and disease states.

Background: Pyrotinib is an irreversible pan-ErbB inhibitor targeting epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), and HER4. This randomized, double-blinded phase 3 study evaluated the efficacy and safety of pyrotinib plus capecitabine for HER2-positive local relapsed or metastatic breast cancer.Methods: Patients who had been treated with trastuzumab and taxanes were randomized (2:1) to receive either oral pyrotinib or placebo (400 mg, qd) plus capecitabine (1,000 mg/m 2 , bid on days 1-14) for 21-day cycles, using stratified block randomization. The primary endpoint was progression-free survival (PFS) per independent review committee. Patients who progressed on placebo plus capecitabine received subsequent pyrotinib monotherapy. This study is registered with ClinicalTrials.gov (NCT02973737), enrollment is closed.

Cell-surface engineering strategies that permit long-lived display of well-defined, functionally active molecules are highly attractive for eliciting desired cellular responses and for understanding biological processes. Current methodologies for the exogenous introduction of synthetic biomolecules often result in short-lived presentations, or require genetic manipulation to facilitate membrane attachment. Herein, we report a cell-surface engineering strategy that is based on the use of a CMP-Neu5Ac derivative that is modified at C-5 by a bifunctional entity composed of a complex synthetic heparan sulfate (HS) oligosaccharide and biotin. It is shown that recombinant ST6GAL1 can readily transfer the modified sialic acid to N-glycans of glycoprotein acceptors of living cells resulting in long-lived display. The HS oligosaccharide is functionally active, can restore protein binding, and allows activation of cell signaling events of HS-deficient cells. The cell-surface engineering methodology can easily be adapted to any cell type and is highly amenable to a wide range of complex biomolecules.