Nanoparticle-Facilitated Membrane Depolarization-Induced Receptor Activation: Implications on Cellular Uptake and Drug Delivery.

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.

Clinically relevant CNT dispersions with exceptionally high dielectric properties for microwave theranostic applications.

We present a formulation for achieving stable high-concentration (up to 20 mg/ml) aqueous dispersions of carbon nanotubes (CNTs) with exceptionally high microwave-frequency (0.5-6 GHz) dielectric properties. The formulation involves functionalizing CVD-synthesized CNTs via sonication in nitric and sulfuric acid. The overall chemical integrity of the CNTs is largely preserved, as demonstrated via physical and chemical characterizations, despite significant shortening and functionalization with oxygen-containing groups. This is attributed to the protected inner walls of double-walled CNTs in the samples. The resulting CNT dispersions show greatly enhanced dielectric properties compared to a CNT-free control. For example, at 3 GHz, the average relative permittivity and effective conductivity across several 20 mg/ml CNT samples were increased by ∼ 70% and ∼ 400%, respectively, compared to the control. These CNT dispersions exhibit the stability and extraordinary microwave properties desired in systemically administered theranostic agents for microwave diagnostic imaging and/or thermal therapy.