Characterization and comparison of two novel nanosystems associated with siRNA for cellular therapy

André, Emilie; Pensado, Andrea; Resnier, Pauline; Braz, Luis; Costa, Ana M. Rosa da; Passirani, Catherine; Sánchez, Alejandro; Montero‐Menei, Claudia N.

doi:10.1016/j.ijpharm.2015.11.020

Cited by 16 publications

(13 citation statements)

References 62 publications

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“…As described above, the biosafety of the sericin-PBLG nanocarrier was validated both in vitro and in vivo , and the high biocompatibility observed demonstrates the further potential for use as in cancer treatment. However, the drug delivery mechanism for sericin-PBLG-DOX is unknown, which is a critical aspect of pharmaceutical research (Andre et al., 2016 ). Nanoscale drugs are considered to be a promising strategy for enhancing the intracellular delivery of drugs.…”

Section: Resultsmentioning

confidence: 99%

Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance

Guo

Deng

et al. 2018

Drug Delivery

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Drug resistance is the major challenge facing cancer chemotherapy and nanoscale delivery systems based on natural materials, such as sericin, are a promising means of overcoming drug resistance. Yet, no attempt of introducing synthetic poly(γ-benzyl-L-glutamate) (PBLG) onto sericin polypeptide to fabricate a facile biocompatible and biodegradable micelle has been tried. Here, we prepared a polypeptide-based amphiphilic polymer containing hydrophilic sericin polypeptide backbone and PBLG side chains via ring-opening polymerization (ROP) strategy. The introduction of PBLG side chains remarkably enhances the stability of sericin micelles in water. Meanwhile, the micelles exhibited a high loading capacity and pH-responsive release ability for antitumor drug doxorubicin (DOX), called sericin-PBLG-DOX. Owing to the excellent cell membrane penetration of sericin-PBLG, the cellular uptake of DOX when loaded into micelles was improved. Subsequently, sericin-PBLG-DOX was transferred into perinuclear lysosomes, where the release rate of DOX was accelerated. Compared to the same dose of DOX, sericin-PBLG-DOX could induce a more efficient anti-tumor effect both in vitro and in vivo, and these micelles have promise for future clinical applications in overcoming cancer drug resistance with good biosafety, enhanced cellular uptake, pH-triggered drug release, efficient anti-tumor effects, and minimized systemic toxicity.

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Section: Resultsmentioning

confidence: 99%

Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance

Guo

Deng

et al. 2018

Drug Delivery

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“…LNCs were formulated, as previously described [38] by mixing 20% w / w Labrafac ® WL 1349 (caprylic-capric acid triglycerides, Gatefossé S.A. Saint-Priest, France), 1.5% w / w Lipoid S75-3 ® (Lecithin, Ludwigshafen, Germany), 17% w / w Kolliphor ® HS 15 (Polyethylene glycol-15-Hydroxystearate PEGHS BASF, Ludwigshafen, Germany), 1.8% w / w NaCl (Prolabo, Fontenay-sous-Bois, France) and 59.8% w / w water (obtained from a Milli-Q system, Millipore, Paris, France) together under magnetic stirring. Briefly, three temperature cycles between 60 and 95 °C were performed to obtain phase inversions of the emulsion.…”

Section: Methodsmentioning

confidence: 99%

A Combinatorial Cell and Drug Delivery Strategy for Huntington’s Disease Using Pharmacologically Active Microcarriers and RNAi Neuronally-Committed Mesenchymal Stromal Cells

et al. 2019

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For Huntington’s disease (HD) cell-based therapy, the transplanted cells are required to be committed to a neuronal cell lineage, survive and maintain this phenotype to ensure their safe transplantation in the brain. We first investigated the role of RE-1 silencing transcription factor (REST) inhibition using siRNA in the GABAergic differentiation of marrow-isolated adult multilineage inducible (MIAMI) cells, a subpopulation of MSCs. We further combined these cells to laminin-coated poly(lactic-co-glycolic acid) PLGA pharmacologically active microcarriers (PAMs) delivering BDNF in a controlled fashion to stimulate the survival and maintain the differentiation of the cells. The PAMs/cells complexes were then transplanted in an ex vivo model of HD. Using Sonic Hedgehog (SHH) and siREST, we obtained GABAergic progenitors/neuronal-like cells, which were able to secrete HGF, SDF1 VEGFa and BDNF, of importance for HD. GABA-like progenitors adhered to PAMs increased their mRNA expression of NGF/VEGFa as well as their secretion of PIGF-1, which can enhance reparative angiogenesis. In our ex vivo model of HD, they were successfully transplanted while attached to PAMs and were able to survive and maintain this GABAergic neuronal phenotype. Together, our results may pave the way for future research that could improve the success of cell-based therapy for HDs.

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“…The use of small interfering RNA (siRNA) is a promising approach to treat human diseases, including inflammatory disorders, viral infections and cancers . siRNA are short double‐stranded RNA molecules (21–23 oligonucleotides base pairs) able to specifically recognize a complementary mRNA, to degrade it and consequently to reduce its translation into proteins . In case of gene therapy, siRNA are exploited in order to decrease the expression of undesired genes.…”

Section: Introductionmentioning

confidence: 99%

Capillary electrophoresis method to determine siRNA complexation with cationic liposomes

et al. 2016

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Small interfering RNA (siRNA) inducing gene silencing has great potential to treat many human diseases. To ensure effective siRNA delivery, it must be complexed with an appropriate vector, generally nanoparticles. The nanoparticulate complex requires an optimal physiochemical characterization and the complexation efficiency has to be precisely determined. The methods usually used to measure complexation in gel electrophoresis and RiboGreen fluorescence-based assay. However, those approaches are not automated and present some drawbacks such as the low throughput and the use of carcinogenic reagents. The aim of this study is to develop a new simple and fast method to accurately quantify the complexation efficiency. In this study, capillary electrophoresis (CE) was used to determine the siRNA complexation with cationic liposomes. The short-end injection mode applied enabled siRNA detection in less than 5 min. Moreover, the CE technique offers many advantages compared with the other classical methods. It is automated, does not require sample preparation and expensive reagents. Moreover, no mutagenic risk is associated with the CE approach since no carcinogenic product is used. Finally, this methodology can also be extended for the characterization of other types of nanoparticles encapsulating siRNA, such as cationic polymeric nanoparticles.

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Characterization and comparison of two novel nanosystems associated with siRNA for cellular therapy

Cited by 16 publications

References 62 publications

Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance

Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance

A Combinatorial Cell and Drug Delivery Strategy for Huntington’s Disease Using Pharmacologically Active Microcarriers and RNAi Neuronally-Committed Mesenchymal Stromal Cells

Capillary electrophoresis method to determine siRNA complexation with cationic liposomes

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