RESUMEN
The siRNA transfection efficiency of nanoparticles (NPs), composed of a superparamagnetic iron oxide core modified with polycationic polymers (poly(hexamethylene biguanide) or branched polyethyleneimine), were studied in CHO-K1 and HeLa cell lines. Both NPs demonstrated to be good siRNA transfection vehicles, but unmodified branched polyethyleneimine (25 kD) was superior on both cell lines. However, application of an external magnetic field during transfection (magnetofection) increased the efficiency of the superparamagnetic NPs. Furthermore, our results reveal that these NPs are less toxic towards CHO-K1 cell lines than the unmodified polycationic-branched polyethyleneimine (PEI). In general, the external magnetic field did not alter the cell's viability nor it disrupted the cell membranes, except for the poly(hexamethylene biguanide)-modified NP, where it was observed that in CHO-K1 cells application of the external magnetic field promoted membrane damage. This paper presents new polycationic superparamagnetic NPs as promising transfection vehicles for siRNA and demonstrates the advantages of magnetofection.
RESUMEN
Borane-mediated reduction of aryl and alkyl ketones with alpha-aryl- and alpha-pyridyloxy groups affords beta-hydroxy ethers in high enantiomeric purity (up to 99% ee) and in good yield, using as catalyst 10 mol % of spiroborate ester 1 derived from (S)-diphenylprolinol. Representative beta-hydroxy ethers are successfully converted to beta-amino ethers, with minor epimerization, by phthalimide substitution under Mitsunobu's conditions followed by hydrazinolysis to obtain primary amino ethers or by imide reduction with borane to afford beta-2,3-dihydro-1H-isoindol ethers. Nonracemic Mexiletine and nAChR analogues with potential biological activity are also synthesized in excellent yield by mesylation of key beta-hydroxy pyridylethers and substitution with five-, six-, and seven-membered ring heterocyclic amines.
