Chowdhury Sayan Mullick, Xie Shawn, Fang Justin, Lee Stephen K, Sitharaman Balaji
Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York 11794, United States.
ACS Biomater Sci Eng. 2016 Dec 12;2(12):2153-2161. doi: 10.1021/acsbiomaterials.6b00338. Epub 2016 Oct 28.
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--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 Ca 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.
药物递送系统（DDSs）的细胞特异性摄取对于实现许多药物的最佳疗效至关重要。广泛采用的促进靶向细胞内药物递送的策略包括将靶向配体（肽或抗体）附着到DDSs上。靶受体突变可能会限制这种方法的有效性。在此，我们通过体外抑制和药物递送研究证明，用名为PEG-DSPE（（1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[氨基（聚乙二醇）]）的两亲聚合物水分散的石墨烯纳米带（GNRs）会诱导膜去极化介导的表皮生长因子受体（EGFR）激活。这种现象不依赖配体，并且EGFR激活是通过细胞外空间的钙离子内流发生的。我们通过体内研究进一步提供证据，表明这种机制可用于促进向过度表达EGFR的肿瘤中有效递送药物。结果表明，瞬时膜去极化促进的细胞受体激活可作为增强细胞内药物递送的替代策略。
