Effect of surface properties on liposomal siRNA delivery

Xia, Yuqiong; Tian, Jie; Chen, Xiaoyuan

doi:10.1016/j.biomaterials.2015.11.056

Cited by 192 publications

(164 citation statements)

References 104 publications

(150 reference statements)

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“…In our work, the ion‐pairs might form between the cationic DOTAP and the anionic lipids on the endosome membrane, which can induce the disassembly of LGCP and allow the release of the complex of TAT‐GNs/Cas9 protein/sgPlk1 plasmid from LGCP. Moreover, the ion‐pairs can facilitate the formation of the inverted hexagonal phase in the binding lipids, which may trigger the membrane fusion between LGCP and endosome membrane, leading to destabilization of endosome membrane 28. On the other hand, the cationic TAT clusters in LGCP may enhance the endosomal escape as well.…”

Section: Resultsmentioning

confidence: 99%

Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a Gold Nanocluster/Lipid Core–Shell Nanocarrier

et al. 2017

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The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR)‐Cas9 (CRISPR‐associated protein) system (CRISPR‐Cas9) is a powerful toolbox for gene‐editing, however, the nonviral delivery of CRISPR‐Cas9 to cells or tissues remains a key challenge. This paper reports a strategy to deliver Cas9 protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV‐1‐transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered into cell nuclei. This strategy is utilized to treat melanoma by designing sgRNA targeting Polo‐like kinase‐1 (Plk1) of the tumor. The nanoparticle (polyethylene glycol‐lipid/GNs/Cas9 protein/sgPlk1 plasmid, LGCP) leads to >70% down‐regulation of Plk1 protein expression of A375 cells in vitro. Moreover, the LGCP suppresses melanoma progress by 75% on mice. Thus, this strategy can deliver protein‐nucleic acid hybrid agents for gene therapy.

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Section: Resultsmentioning

confidence: 99%

Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a Gold Nanocluster/Lipid Core–Shell Nanocarrier

et al. 2017

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“…As serum proteins are negatively charged, they are prone to interact with positively charged nanoparticles thus leading to aggregation through electrostatic interactions. So the negatively charged Plain-lip showed good stability because of the repulsion between the liposomes and serum proteins [24].…”

Section: Serum Stabilitymentioning

confidence: 99%

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Ran

Middelberg

Zhao

2016

Colloids and Surfaces B: Biointerfaces

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Graphical abstract Highlights Targeted liposomes can be prepared in the one-step microfluidic device  Size and surface properties can be controlled easily  This microfluidic method directed targeted liposomes possess selective cell uptake enhancement in both 2D and 3D model.  At the same time, these liposomes can reduce phagocytosis. AbstractNanotechnology has started a new era in engineering multifunctional nanoparticles for diagnosis and therapeutics by incorporating therapeutic drugs, targeting ligands, stimuliresponsive release and imaging molecules. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield and high production cost, hence difficulties in clinical translation. Herein we report a one-step microfluidic method for making multifunctional liposomes. Three formulations were prepared using this simple method, including plain liposomes, PEGylated liposomes and folic acid functionalised liposomes, all with a fluorescence dye encapsulated for imaging. The size and surface properties of these liposomes can be precisely controlled by simply tuning the flow rate ratio and the ratio of the lipids to PEGylated lipid (DSPE-PEG2000) and to the DSPE-PEG2000-Folate, respectively. The synthesised liposomes remained stable under mimic serum conditions.Compared to the plain liposomes and PEGylated liposomes, the targeted folic acid functionalised liposomes exhibited enhanced cellular uptake by the FA receptor positive SKOV3 cells, but not the negative MCF7 cells, and this enhanced uptake could be inhibited by adding excess free folic acid, indicating high specificity of FA ligand-receptor endocytosis.Further evaluation using the 3D tumour spheroid model also showed higher internalisation of the targeted liposome formulation in comparison with the PEGylated one. To the best of our knowledge, this work demonstrates for the first time the versatility of this microfluidic method for making different liposome formulations in a single step, their superior physicochemical properties as well as the enhanced cellular uptake and tumour spheroid uptake of the targeted liposomes.

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“…[1][2][3] In gene therapy, small interfering RNA (siRNA) has come into the spotlight; siRNA molecules consisting of 21-23 nucleotides can bind to target genes and degrade target messenger RNA with complementary sequences to produce a therapeutic effect. According to the literature, various cancers including cancers of the breasts, bladder, lungs, ovaries and prostate have been inhibited by siRNA in the recent years.…”

Section: Introductionmentioning

confidence: 99%

Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis

Park¹,

Huang

Jin³

et al. 2016

IJN

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Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.

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Effect of surface properties on liposomal siRNA delivery

Cited by 192 publications

References 104 publications

Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a Gold Nanocluster/Lipid Core–Shell Nanocarrier

Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a Gold Nanocluster/Lipid Core–Shell Nanocarrier

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis

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