Anginex lipoplexes for delivery of anti-angiogenic siRNA

Yousefi, Afrouz; Bourajjaj, Meriem; Babae, Negar; Noort, Paula I. van; Schaapveld, Roel Q.J.; Beijnum, Judy R. van; Storm, Gert; Schiffelers, Raymond M.; Mastrobattista, Enrico

doi:10.1016/j.ijpharm.2014.06.028

Cited by 8 publications

(5 citation statements)

References 54 publications

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“…To use RNA in a therapeutic way, it has to reach the cytosol of cells. Delivery vehicles for siRNA and other nucleic acids include inorganic nanoparticles [27][28][29], lipidbased [30][31][32][33][34][35] or polymeric formulations [36][37][38][39][40][41][42][43][44][45][46][47]. In the field of polymer delivery, solid phase-supported synthesis (SPS) has been applied for the production of sequence-defined oligomers [48][49][50].…”

Section: Introductionmentioning

confidence: 99%

EGF receptor targeted lipo-oligocation polyplexes for antitumoral siRNA and miRNA delivery

et al. 2016

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Antitumoral siRNA and miRNA delivery was demonstrated by epidermal growth factor receptor (EGFR) targeted oligoaminoamide polyplexes. For this purpose, the T-shaped lipo-oligomer 454 was used to complex RNA into a core polyplex, which was subsequently functionalized with the targeting peptide ligand GE11 via a polyethylene glycol (PEG) linker. To this end, free cysteines on the surface of 454 polyplex were coupled with a maleimide-PEG-GE11 reagent (Mal-GE11). Resulting particles with sizes of 120-150 nm showed receptor-mediated uptake into EGFR-positive T24 bladder cancer cells, MDA-MB 231 breast cancer cells and Huh7 liver cancer cells. Furthermore, these formulations led to ligand-dependent gene silencing. RNA interference (RNAi) triggered antitumoral effects were observed for two different therapeutic RNAs, a miRNA-200c mimic or EG5 siRNA. Using polyplexes modified with a ratio of 0.8 molar equivalents of Mal-GE11, treatment of T24 or MDA-MB 231 cancer cells with miR-200c led to the expected decreased proliferation and migration, changes in cell cycle and enhanced sensitivity towards doxorubicin. Delivery of EG5 siRNA into Huh7 cells resulted in antitumoral activity with G2/M arrest, triggered by loss of mitotic spindle separation and formation of mono-astral spindles. These findings demonstrate the potential of GE11 ligand-containing RNAi polyplexes for cancer treatment.

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Section: Introductionmentioning

confidence: 99%

EGF receptor targeted lipo-oligocation polyplexes for antitumoral siRNA and miRNA delivery

et al. 2016

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“…Thus far, few targeted nanoparticle formulations have progressed toward the clinic [64], and most systems have relied on trapping in the tumor environment by means of vascular leakage. Nevertheless, more efficient delivery can be expected with targeted nanoparticles, either toward the tumor cells, or toward the tumor endothelium [36, 65]. Furthermore, the loading of both small molecule drugs and miRNA therapeutics in a single nanocarrier offers the potential of efficient delivery and synergistic effects [30].…”

Section: Mirna-based Therapymentioning

confidence: 99%

“…The targeted particles here were aimed at the tumor endothelial marker αVβ3 integrin, thereby effectively classifying the second approach as a combination therapy. As such, the potential for using tumor vasculature targets for (liposomal) miRNA delivery is underscored by this study, as well as by another study from this group combining galectin-1 targeted formulations for VEGFR2 siRNA [65, 76]. …”

Section: Anti-angiogenic Mirna-based Combination Therapymentioning

confidence: 99%

miRNAs: micro-managers of anticancer combination therapies

et al. 2017

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Angiogenesis is one of the hallmarks of cancer progression and as such has been considered a target of therapeutic interest. However, single targeted agents have not fully lived up to the initial promise of anti-angiogenic therapy. Therefore, it has been suggested that combining therapies and agents will be the way forward in the oncology field. In recent years, microRNAs (miRNAs) have received considerable attention as drivers of tumor development and progression, either acting as tumor suppressors or as oncogenes (so-called oncomiRs), as well as in the process of tumor angiogenesis (angiomiRs). Not only from a functional, but also from a therapeutic view, miRNAs are attractive tools. Thus far, several mimics and antagonists of miRNAs have entered clinical development. Here, we review the provenance and promise of miRNAs as targets as well as therapeutics to contribute to anti-angiogenesis-based (combination) treatment of cancer.

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“…Finally, it is necessary to prevent off-target effects including nucleotide-based immune activation ( 278 , 279 ). To do this, delivery systems have been developed to protect siRNA from nuclease degradation and facilitate cellular uptake at target sites [chemically modified RNAs ( 280 , 281 ), nanoparticles ( 37 , 92 , 93 , 282 ) and lipoplexes ( 283 )]. These strategies have demonstrated effectiveness to some extent.…”

Section: Current Galectin Inhibitorsmentioning

confidence: 99%

Inhibition of galectins in cancer: Biological challenges for their clinical application

Laderach

Compagno

2023

Front. Immunol.

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Galectins play relevant roles in tumor development, progression and metastasis. Accordingly, galectins are certainly enticing targets for medical intervention in cancer. To date, however, clinical trials based on galectin inhibitors reported inconclusive results. This review summarizes the galectin inhibitors currently being evaluated and discusses some of the biological challenges that need to be addressed to improve these strategies for the benefit of cancer patients.

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Anginex lipoplexes for delivery of anti-angiogenic siRNA

Cited by 8 publications

References 54 publications

EGF receptor targeted lipo-oligocation polyplexes for antitumoral siRNA and miRNA delivery

EGF receptor targeted lipo-oligocation polyplexes for antitumoral siRNA and miRNA delivery

miRNAs: micro-managers of anticancer combination therapies

Inhibition of galectins in cancer: Biological challenges for their clinical application

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