Multifunctional
poly(ethylene glycol)-block-poly(lactic
acid) (PEG-b-PLA) nanoparticles for cancer cell targeting
and imaging have been designed by a combination of ring-opening polymerization
and “click” chemistry. Nanoparticles containing both
a targeting ligand and a fluorescent probe were prepared by blending
PLA-b-PEG–ligand, PLA-b-PEG–fluorescent
probe, and PLA-b-PEG–OMe copolymers at the
molar ratios necessary to achieve the desired surface ligand and fluorescent
probe densities. This strategy has been illustrated by the preparation
of a large library of a variety of nanoparticles, such as ligand-decorated
nanoparticles (with biotin, folic acid or anisamide), fluorescent
nanoparticles (UV–vis or near-infrared dyes), and multifunctional
nanoparticles decorated with a targeting ligand and a fluorescent
probe. Successful targeting was demonstrated by surface plasmon resonance
and in vitro experiments on different cancer cell lines.
A definition of a partial agonists serotonin 5-HT3 pharmacophore was carried out by considering a three-dimensional model which correlates the chemical structures of series of piperazinopyrrolothienopyrazines, piperazinopyridopyrrolopyrazines, piperazinopyrroloquinolaxines, piperazinopyridopyrroloquinoxalines, aminoalkyloximinopyrroloindoles, aminoalkyloximinothienopyrrolizines, and aminoalkyloximinopyrrolizines with the biological affinities. The model is formed by five features corresponding to two hydrogen bond acceptors, one aromatic ring, one hydrophobic group, and one positive ionizable site (quaternary ammonium ions). The nature of the features and the distances between them explain the partial agonist activities of these compounds.
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