Drug-Initiated Synthesis of Cladribine-Based Polymer Prodrug Nanoparticles: Biological Evaluation and Structure Activity Relationships

International audienceBy using two reversible deactivation radical polymerization techniques, either nitroxide-mediated polymerization or reversible addition-fragmentation chain transfer polymerization, the "drug-initiated" approach was applied to cladribine (CdA) as an anticancer drug to synthesize small libraries of well-defined and self-stabilized CdA-based polymer prodrug nanoparticles, differing from the nature and the molar mass of the grown polymer, and the nature of the linker between CdA and the polymer, thus allowing structure-cytotoxicity relationships to be determined. Their biological evaluation was investigated in vitro on L1210 cancer cells. The preparation of fluorescent CdA-based nanoparticles with excellent imaging ability was also reported by applying the "drug-initiated" approach to an aggregation-induced emission-active dye

Neurochemical coding of enteric neurons in adult and embryonic zebrafish (<i>Danio rerio</i>)

Although the morphology and development of the zebrafish enteric nervous system have been extensively studied, the precise neurochemical coding of enteric neurons and their proportional enteric distribution are currently not known. By using immunohistochemistry, we determined the proportional expression and coexpression of neurochemical markers in the embryonic and adult zebrafish intestine. Tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) were observed only in nerve fibers, whereas other markers were also detected in neuronal cell bodies. Calretinin and calbindin had similar distributions. In embryos, all markers, except for choline acetyltransferase (ChAT) and TH, were present from 72 hours postfertilization. Nitrergic neurons, evenly distributed and remaining constant in time, constituted the major neuronal subpopulation. The neuronal proportions of the other markers increased during development and were characterized by regional differences. In the adult, all markers examined were expressed in the enteric nervous system. A large percentage of enteric neurons displayed calbindin and calretinin, and serotonin was the only marker showing significant distribution differences in the three intestinal regions. Colocalization studies showed that serotonin was not coexpressed with any of the other markers. At least five neuronal subpopulations were determined: a serotonergic, a nitrergic noncholinergic, two cholinergic nonnitrergic subpopulations along with one subpopulation expressing both ChAT and neuronal nitric oxide synthase. Analysis of nerve fibers revealed that nitrergic neurons coexpress VIP and PACAP, and that nitrergic neurons innervate the tunica muscularis, whereas serotonergic and cholinergic nonnitrergic neurons innervate the lamina propria and the tunica muscularis