Aptamer-Dendrimer Bioconjugates for Targeted Delivery of miR-34a Expressing Plasmid and Antitumor Effects in Non-Small Cell Lung Cancer Cells

Wang, Hongmei; Zhao, Xin; Guo, Chenyu; Ren, Dunqiang; Zhao, Yandong; Wu, Xiao; Jiao, Wenjie

doi:10.1371/journal.pone.0139136

Cited by 66 publications

(28 citation statements)

References 40 publications

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“…In order to prevent the toxicity of PAMAMs, substances with an opposite charge, such as polyethylene glycol (PEG) have been conjugated (Jiang et al, ; Labieniec‐Watala, Karolczak, Siewiera, & Watala, ). Aptamer sequences, as negatively charged single‐strand oligonuclotides, were conjugated with PAMAMs to increase cellular uptake of miR‐34a‐containing plasmid in lung cancer cells in vitro (Wang et al, ). Another modification for refinement of dendrimer‐based delivery of miRNA is diversification of chemical structure.…”

Section: Microrna Replacement Therapymentioning

confidence: 99%

Treating cancer with microRNA replacement therapy: A literature review

Hosseinahli¹,

Aghapour²,

Duijf

et al. 2018

Journal Cellular Physiology

258

184

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microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally by interfering with the translation of one or more target mRNAs. The unique miRNA sequences are involved in many physiological and pathological processes. Dysregulation of miRNAs contributes to the pathogenesis of all types of cancer. Notably, the diminished expression of tumor suppressor miRNAs, such as members of the Let-7 and miR-34 family, promotes tumor progression, invasion and metastasis. The past lustrum in particular, has witnessed substantial improvement of miRNA replacement therapy. This approach aims to restore tumor suppressor miRNA function in tumor cells using synthetic miRNA mimics or miRNA expression plasmids. Here, we provide a comprehensive review of recent advances in miRNA replacement therapy for treatment of cancer and its advantages over conventional gene therapy. We discuss a wide variety of delivery methods and vectors, as well as obstacles that remain to be overcome. Lastly, we review efforts to reverse epigenetic alterations, which affect miRNA expression in cancer cells, and the promising observation that restoring miRNA function re-sensitizes resistant tumor cells to chemotherapeutic drugs. The fact that various miRNA replacement therapies are currently in clinical trial demonstrates the great potential of this approach to treat cancer.

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Section: Microrna Replacement Therapymentioning

confidence: 99%

Treating cancer with microRNA replacement therapy: A literature review

Hosseinahli¹,

Aghapour²,

Duijf

et al. 2018

Journal Cellular Physiology

258

184

View full text Add to dashboard Cite

show abstract

“…miR-34a is a recently identified miRNA that has been associated with tumor development, vascular injury, cell proliferation and apoptosis (27). Furthermore, overexpression of miR-34a may inhibit the proliferation and migration of various tumor cells, including lung, colon and gastric cancer cells (28,29). Overexpression of miR-34a may also induce the apoptosis of human brain glioblastoma cells (30).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms in vascular injury induced by hypertension: Expression and role of microRNA‑34a

Liu

Cheng

et al. 2017

Exp Ther Med

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Abstract. The aim of the present study was to investigate the expression and function of microRNA (miR)-34a in patients with primary hypertension. The expression of miR-34a was measured in the peripheral blood of 50 patients with primary hypertension and 28 normal controls by reverse transcription quantitative polymerase chain reaction. In addition, human umbilical vein endothelial cells (HUVECs) were transfected with an miR-34a inhibitor to suppress the expression of miR-34a, and the proliferation, migration and cell cycle distribution of HUVECs were measured by Cell Counting Kit-8, Transwell and flow cytometry assays. The target of miR-34a was also predicted by bioinformatics analysis and verified by a dual-luciferase reporter gene assay and western blot analysis. miR-34a was significantly upregulated in the peripheral blood of patients with hypertension when compared with controls (P<0.05), and upregulation of miR-34a was associated with a higher clinical stage of hypertension (phase III; P<0.05). In vitro experiments demonstrated that inhibition of miR-34a promoted the proliferation, migration and G1/S transition of HUVECs, relative to scramble-miR controls (P<0.05). Furthermore, transforming growth factor β-induced factor homeobox 2 (TIGF2) was predicted and verified to be a direct target of miR-34a. Collectively, these data suggested that miR-34a was upregulated in the peripheral blood of patients with hypertension, and that upregulated miR-34a may promote vascular endothelial injury by targeting TIGF2.

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“…In addition to drug delivery, the aptamer-conjugated dendrimer has been successfully used for miR delivery [125]. The tumor suppressor miR-34a was encapsulated into a dendrimer linked to an anti-lung cancer cells aptamer (S6), significantly improving miR cellular uptake in NSCLC cells.…”

Section: Aptamer-nanoparticles Systemsmentioning

confidence: 99%

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

2016

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The selective delivery of drugs in a cell- or tissue-specific manner represents the main challenge for medical research; in order to reduce the occurrence of unwanted off-target effects. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules due to their ability to bind with high affinity to specific ligands; their high chemical flexibility; as well as tissue penetration capability. To date, different aptamer-drug systems and aptamer–nanoparticles systems, in which nanoparticles function together with aptamers for the targeted delivery, have been successfully developed for a wide range of therapeutics, including toxins; peptides; chemotherapeutics and oligonucleotides. Therefore, aptamer-mediated drug delivery represents a powerful tool for the safe and effective treatment of different human pathologies, including cancer; neurological diseases; immunological diseases and so on. In this review, we will summarize recent progress in the field of aptamer-mediated drug delivery and we will discuss the advantages, the achieved objectives and the challenges to be still addressed in the near future, in order to improve the effectiveness of therapies.

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Aptamer-Dendrimer Bioconjugates for Targeted Delivery of miR-34a Expressing Plasmid and Antitumor Effects in Non-Small Cell Lung Cancer Cells

Cited by 66 publications

References 40 publications

Treating cancer with microRNA replacement therapy: A literature review

Treating cancer with microRNA replacement therapy: A literature review

Molecular mechanisms in vascular injury induced by hypertension: Expression and role of microRNA‑34a

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

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