Abstract
Cell-specific uptake of drug delivery systems (DDSs) are crucial to achieve optimal efficacy of many drugs. Widely employed strategies to facilitate targeted intracellular drug delivery involves attachment of targeting ligands (peptides or antibodies) to DDSs. Target receptors mutations can limit the effectiveness of this approach. Herein, we demonstrate, through in vitro inhibitory and drug delivery studies, that graphene nanoribbons (GNRs), water dispersed with the amphiphilic polymer called PEG-DSPE ((1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N [amino (polyethylene glycol)]) (induce membrane depolarization-mediated epidermal growth factor receptor (EGFR) activation. This phenomenon is ligand-independent and EGFR activation occurs via influx of Ca2+ ions from the extracellular space. We further provide evidence, through in vivo studies, that this mechanism could be exploited to facilitate efficacious drug delivery into tumors that overexpress EGFR. The results suggest that transient membrane depolarization-facilitated cell receptor activation can be employed as an alternate strategy for enhanced intracellular drug delivery.
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