Dataset Information

Aptamer-Functionalized Exosomes: Elucidating the Cellular Uptake Mechanism and the Potential for Cancer-Targeted Chemotherapy.

ABSTRACT: Exosomes (Exos) are nanoscale natural vehicles for transporting biomolecules to facilitate cell-to-cell communication, indicating a high potential of them for delivering therapeutics/diagnostics. To improve their delivery capacity, a simple, noninvasive, and efficient strategy for functionalizing Exos with effective targeting ligands as well as elucidation of the cellular uptake mechanism of these functionalized Exos was found be to necessary, but remained a challenge. In this work, we used diacyllipid-aptamer conjugates as the targeting ligand to develop an aptamer-functionalized Exos (Apt-Exos) nanoplatform for cell type-specific delivery of molecular therapeutics. The cellular uptake mechanism of Apt-Exos was investigated in details, and distinct behavior was observed in comparison to free Exos. By combining the excellent molecular recognition capability of aptamers and the superiority of Exos as natural vehicles, Apt-Exos can efficiently deliver molecular drugs/fluorophores to target cancer cells, providing a promising delivery platform for cancer theranostics.

SUBMITTER: Zou J

PROVIDER: S-EPMC6662586 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Aptamer-Functionalized Exosomes: Elucidating the Cellular Uptake Mechanism and the Potential for Cancer-Targeted Chemotherapy.

Zou Jianmei J Shi Muling M Liu Xiaojing X Jin Cheng C Xing Xiaojing X Qiu Liping L Tan Weihong W

Analytical chemistry 20190124 3

Exosomes (Exos) are nanoscale natural vehicles for transporting biomolecules to facilitate cell-to-cell communication, indicating a high potential of them for delivering therapeutics/diagnostics. To improve their delivery capacity, a simple, noninvasive, and efficient strategy for functionalizing Exos with effective targeting ligands as well as elucidation of the cellular uptake mechanism of these functionalized Exos was found be to necessary, but remained a challenge. In this work, we used diac ...[more]

PMID: 30620179

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Project description:BackgroundBoth TGFβ and estradiol (E2), a form of estrogen, are pro-fibrotic in the skin. In the connective tissue disease, systemic sclerosis (SSc), both TGFβ and E2 are likely pathogenic. Yet the regulation of TGFβ in E2-induced dermal fibrosis remains ill-defined. Elucidating those regulatory mechanisms will improve the understanding of fibrotic disease pathogenesis and set the stage for developing potential therapeutics. Using E2-stimulated primary human dermal fibroblasts in vitro and human skin tissue ex vivo, we identified the important regulatory proteins for TGFβ and investigated the extracellular matrix (ECM) components that are directly stimulated by E2-induced TGFβ signaling.MethodsWe used primary human dermal fibroblasts in vitro and human skin tissue ex vivo stimulated with E2 or vehicle (ethanol) to measure TGFβ1 and TGFβ2 levels using quantitative PCR (qPCR). To identify the necessary cell signaling proteins in E2-induced TGFβ1 and TGFβ2 transcription, human dermal fibroblasts were pre-treated with an inhibitor of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway, U0126. Finally, human skin tissue ex vivo was pre-treated with SB-431542, a TGFβ receptor inhibitor, and ICI 182,780, an estrogen receptor α (ERα) inhibitor, to establish the effects of TGFβ and ERα signaling on E2-induced collagen 22A1 (Col22A1) transcription.ResultsWe found that expression of TGFβ1, TGFβ2, and Col22A1, a TGFβ-responsive gene, is induced in response to E2 stimulation. Mechanistically, Col22A1 induction was blocked by SB-431542 and ICI 182,780 despite E2 stimulation. Additionally, inhibiting E2-induced ERK/MAPK activation and early growth response 1 (EGR1) transcription prevents the E2-induced increase in TGFβ1 and TGFβ2 transcription and translation.ConclusionsWe conclude that E2-induced dermal fibrosis occurs in part through induction of TGFβ1, 2, and Col22A1, which is regulated through EGR1 and the MAPK pathway. Thus, blocking estrogen signaling and/or production may be a novel therapeutic option in pro-fibrotic diseases.

Dataset Information

Aptamer-Functionalized Exosomes: Elucidating the Cellular Uptake Mechanism and the Potential for Cancer-Targeted Chemotherapy.

Publications

Aptamer-Functionalized Exosomes: Elucidating the Cellular Uptake Mechanism and the Potential for Cancer-Targeted Chemotherapy.

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