Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma

Zhang, Mengzi; Zhou, Xingyao; Wang, Bo; Yung, Bryant C.; Lee, Ly J.; Ghoshal, Kalpana; Lee, Robert J.

doi:10.1016/j.jconrel.2013.03.020

Cited by 79 publications

(67 citation statements)

References 43 publications

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“…Modification of the oligonucleotide backbone also increases the stability of the miRs against enzymatic degradation and facilitates direct delivery to cells without the need for transfection. However, these methods are limited by their efficacy in vivo by serum nucleases, lysosomal degradation, and non-specific absorption [20]. …”

Section: Discussionmentioning

confidence: 99%

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Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine

Yin

et al. 2017

Cell Physiol Biochem

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Background/Aims: MicroRNA-21 is an oncogenic miR (oncomiR) frequently elevated in gastric cancer (GC). Overexpression of miR-21 decreases the sensitivity of GC cells to 5-fluorouridine (5-Fu) and trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including anti-miRNA oligonucleotides (AMOs). This study is a continuation of earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target GC with HER2 receptor over-expression using anti-miRNA-21 (AMO-21) and 5-Fu. Methods: HER-PEG-PCL NPs were prepared by one-step carbodiimide coupling using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAc) and Sulfo-NHS in aqueous phase. Covalent coupling of amino groups at the surface of PEG-PCL with the carboxyl groups of trastuzumab was analyzed by X-ray photoelectron spectroscopy (XPS). AMO-21/5-Fu NPs were formulated by a double-emulsion solvent evaporation technique. The cell line specificity, cellular uptake and AMO-21 delivery were investigated through the rhodamine-B-labeled 6-carboxyfluorescein (FAM)-AMO-21-PEG-PCL NPs coated with or without the antibody in both Her2-positive (NUGC4) and negative GC cells (SGC7901) visualized by fluorescence microscopy. The cytotoxicity of the HER-PEG-PCL NPs encapsulating AMO-21 was evaluated by MTT and apoptosis. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to examine miR-21 and phosphatase and tensin homolog (PTEN) and Sprouty2 expression in GC cell lines. The antitumor effects of AMO-21/5-Fu NPs were compared with other groups in xenograft gastric cancer mice. Results: The antibody conjugates significantly enhanced the cellular uptake of NPs. The AMO-21/5-Fu NPs effectively suppressed the target miRNA expression in GC cells, which further up-regulated PTEN and Sprouty2. As a result, the sensitivity of HER2-expressing gastric cancer to trastuzumab and 5-Fu were enhanced both in vitro and in vivo. The approach enhanced the targeting by trastuzumab as well as antibody-dependent cellular cytotoxicity (ADCC) of immune effector cells Conclusions: Taken together, the results provide insight into the biological and clinical potential of targeted AMO-21 and 5-Fu co-delivery using modified trastuzumab for GC treatment.

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Section: Discussionmentioning

confidence: 99%

“…Nanodelivery systems have been shown to overcome the challenges posed by AMOs in therapeutic drug delivery in cancer using miRNA interference [20, 21]. The challenges of effective gene silencing relate to active recognition of target cells, without affecting normal cells [22].…”

Section: Introductionmentioning

confidence: 99%

Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine

Yin

et al. 2017

Cell Physiol Biochem

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“…Its intravenous injection has allowed the efficient diffusion of molecules of anti-miR155 to the liver of wild-type mice, leading to a preferential accumulation of anti-miR-155 in hepatocytes and upregulation of miR-155 target genes. 92 To date, no studies have compared different formulations in the same preclinical model or with the same molecule, so a comparative assessment of the different formulations in terms of efficacy and safety of delivery is difficult. However, data emerging from recent studies strongly suggest the usefulness of nanotechnology approaches for implementing miRNAbased therapeutics against HCC.…”

Section: Nanotechnologies For In Vivo Delivery Of Mirnasmentioning

confidence: 99%

Emerging role of microRNAs in the treatment of hepatocellular carcinoma

Callegari¹,

Domenicali²,

Gramantieri³

et al. 2015

GICTT

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Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA)-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma.

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“…Trang and colleagues [23] successfully delivered, systemically, synthetic miR-34a and let-7 mimics targeting lung tissues by using a neutral lipid emulsion and caused a reduction in lung tumor in mice. Zhang et al [24] designed a hepatocyte-targeting ligand to increase the efficiency of anti-miR-155 targeted delivery. These previous methods resulted in the production of strong antitumor effects of miRNAs.…”

Section: Research Highlightmentioning

confidence: 99%

Cholesterol-conjugated let-7a miRNA mimics: promising tools for HCC systemic

Liu¹,

Li²,

Xia³

et al. 2015

RNA Dis

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Let-7 microRNA (miRNA) family members have been demonstrated to have potential therapeutic value in vitro and in vivo as tumor suppressors that act by regulating Ras at a posttranscriptional level. Previous studies on these miRNAs have primarily focused on certain cancers in which mutation and abnormal activation of k-ras/K-Ras occur, such as lung cancer and pancreatic cancers. However, the antitumor potential of let-7 in the case of hepatocellular carcinoma (HCC) has remained untested. Moreover, a major hurdle that limits the clinical use of miRNAs through systemic delivery, including the delivery of let-7 for HCC therapy, is the lack of an effective carrier for targeting tumors. Recently, we confirmed the antitumor efficacy of cholesterol-conjugated let-7a mimics ("Chol-let-7a") in vitro and in vivo and verified-for the first time-that Chol-let-7a can effectively carry let-7a to orthotopic tumors in the liver and successfully inhibit tumor growth in a preclinical model when delivered systemically. We also evaluated for the first time the potential damages that Chol-let-7a could cause to the liver and kidney at histological and ultrastructural levels after long-term systemic delivery, in which Chol-let-7a mainly reached and remained at these organs. Lastly, we showed that Chol-let-7a downregulated all 3 human ras/Ras at transcriptional and translational levels and primarily functioned in the cytoplasm. Overall, our data suggest that the use of cholesterol-conjugated miRNAs is a promising tool for HCC systemic therapy.

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Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma

Cited by 79 publications

References 43 publications

Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine

Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine

Emerging role of microRNAs in the treatment of hepatocellular carcinoma

Cholesterol-conjugated let-7a miRNA mimics: promising tools for HCC systemic

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