Fluorinated amphiphiles are gaining attention in nanomedicine for their unique self-assembly properties and stability, offering opportunities for intracellular drug delivery platforms. We synthesized a tunable series of “fluorosomes” (amine, glutamine, glutamic acid, succinic acid, folate terminus, FITC reporter) based on monodisperse poly(ethylene glycol) (PEG) that spontaneously assemble into nanoparticles with terminal-group-dependent ζ-potentials and morphologies (DLS/TEM). Using a suite of cell lines, we examined cellular uptake, intracellular localization, and cytotoxicity, revealing that despite the superhydrophobic nature of longer fluorinated chains, surface charge still plays a role in modulating nanoparticle - cell interactions. Confocal microscopy revealed a distinct and conserved perinuclear distribution pattern consistent with an endoplasmic reticulum association. This suggests that the observed trafficking occurs predominantly in the proximity of the ER and is largely independent of terminal charge, with folate representing a notable exception. The intracellular distribution pattern suggests a potential preference for nonlysosomal trafficking pathways, possibly involving caveolae-mediated endocytosis, although further mechanistic studies are required to confirm this hypothesis. In vivo NIR imaging of charged variants showed rapid hepatic accumulation, followed by hepatobiliary transit to the intestine and residual signals in the kidneys and lymph nodes through 24–48 h. These data position fluorosomes as possible intracellular carriers for future nanomedicine applications.
Vratović et al. (Thu,) studied this question.