Dataset Information

Tailored Lipoprotein-Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor-Stimulated Macropinocytosis.

ABSTRACT: Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein-like nanostructure is developed to amplify their internalization into GICs through receptor-stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor-stimulated macropinocytosis pathway in GICs, this CXCR4 receptor-stimulated lipoprotein-like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA-34a in the core, this tailored SLNP reduces sex-determining region Y-box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs-bearing mice. Taken together, a tailored lipoprotein-based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor-stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma.

SUBMITTER: Jiang G

PROVIDER: S-EPMC7055550 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Tailored Lipoprotein-Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor-Stimulated Macropinocytosis.

Jiang Gan G Chen Huan H Huang Jialin J Song Qingxiang Q Chen Yaoxing Y Gu Xiao X Jiang Zhenhuan Z Huang Yukun Y Lin Yingying Y Feng Junfeng J Jiang Jiyao J Bao Yinghui Y Zheng Gang G Chen Jun J Chen Hongzhuan H Gao Xiaoling X

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200120 5

Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein-like nanostructure is developed to amplify their internalization into GICs ...[more]

PMID: 32154087

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Project description:Transport of therapeutic agents across epithelial barriers is an important element in drug delivery. Transepithelial flux is widely used as a measure of transit across an epithelium, however it is most typically employed as a relative as opposed to absolute measure of molecular movement. Here, we have used the calcium switch approach to measure the maximum rate of paracellular flux through unencumbered intercellular junctions as a method to calibrate the flux rates for a series of tracers ranging in 0.6-900kDa in size across barriers composed of human colon epithelial (Caco-2) cells. We then examined the effects of nanostructured films (NSFs) on transepithelial transport. Two different NSF patterns were used, Defined Nanostructure (DN) 2 imprinted on polypropylene (PP) and DN3 imprinted on polyether ether ketone (PEEK). NSFs made direct contact with cells and decreased their barrier function, as measured by transepithelial resistance (TER), however cell viability was not affected. When NSF-induced transepithelial transport of Fab fragment (55kDa) and IgG (160kDa) was measured, it was unexpectedly found to be significantly greater than the maximum paracellular rate as predicted using cells cultured in low calcium. These data suggested that NSFs stimulate an active transport pathway, most likely transcytosis, in addition to increasing paracellular flux. Transport of IgG via transcytosis was confirmed by immunofluorescence confocal microscopy, since NSFs induced a significant level of IgG endocytosis by Caco-2 cells. Thus, NSF-induced IgG flux was attributable to both transcytosis and the paracellular route. These data provide the first demonstration that transcytosis can be stimulated by NSFs and that this was concurrent with increased paracellular permeability. Moreover, NSFs with distinct architecture paired with specific substrates have the potential to provide an effective means to regulate transepithelial transport in order to optimize drug delivery.

Dataset Information

Tailored Lipoprotein-Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor-Stimulated Macropinocytosis.

Publications

Tailored Lipoprotein-Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor-Stimulated Macropinocytosis.

Similar Datasets

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