Proton sponge mechanism

MCF-7 cells and their xenograph tumors, and compared with DOX-loaded pH-insensitive micelles made of PLLA-PEG with folate targeting groups (PHlM/f) [99]. The cellular localization of the nanoparticles was confirmed by confocal microscopy (Fig. 10.13). DOX delivered by PHSM/f was found uniformly distributed in the cytosol as well as in the nucleus, while DOX/PHlM/f was entrapped in endosome and multivesicular bodies. It was thus hypothesized that PHis, which is known to have an endosomal membrane-disruption activity induced by a proton sponge mechanism of its imidazole groups [209, 210], disrupted the compartment membrane and released DOX into the cytosol. As a result, DOX/PHSM/f showed much higher in vitro and in vivo anticancer activities toward DOX-resistant cells (Fig. 10.14). 

Scheme 14 The proposed proton sponge mechanism of endosmnal escape. (A) Polyplexes enclosed in an endosrane after endocytosis. (B) Due to the pH buffering in the taidosome, the protons continue to be pumped into the vesicle, resulting in CP influx and an increase in the osmolarity inside the endosomal vesicle. (C) Because of the osmolarity increase, water passes into the endosomal vesicle. (D) The increase in water voltune results in the swelling of the endosomal compartment until it ruptures. (E) Release of the polyplex into the cytoplasm, which leads to nuclear uptake of DNA. Reprinted with permission from [119]. Copyright 2011 Elsevier...

From a mixture of the dicarbaborane arachnoA -G i n, excess NaH, 2 equiv. proton sponge, and 3 equiv. PCI3 the triphosphacarbaborane 4-CI l3- /spectroscopical investigations and quantum mechanical calculations.129... 

The kinetics and mechanism of proton transfer from diarylcyanomethanes to a proton-sponge, c/i-l,2-bis(diethylaminomethyl)cyclohexane, in acetonitrile has been studied. 

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