Analysis of lipid nanoparticles by Cryo-EM for characterizing siRNA delivery vehicles

Crawford, Randy; Dogdas, Belma; Keough, Edward; Haas, Robert; Wepukhulu, Wickliffe; Krotzer, Steven; Burke, Paul A.; Sepp‐Lorenzino, Laura; Bagchi, Ann D.; Howell, Bonnie J.

doi:10.1016/j.ijpharm.2010.10.025

Cited by 69 publications

(69 citation statements)

References 21 publications

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“…However, the mean sizes of the liposomal complexes estimated through DLS typical measurements were relatively higher than those obtained from TEM micrographs, which is likely a consequence of the enhanced scattering from the minimal number of aggregated vesicles that are presented, even at the high dilutions used in DLS measurements. The conflicting mean particle size estimated by DLS and TEM have also been reported in the recent literature [24,25].…”

Section: Discussionmentioning

confidence: 98%

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

Qiu

Cai

Wang

et al. 2015

J Incl Phenom Macrocycl Chem

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Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. Barbigerone (Bar), an anticancer isoflavone, is water insoluble and an effective delivery route is through encapsulation in cyclodextrins (CDs) followed by a second encapsulation in liposomes. In this study, Bar or its inclusion complex [Bar/2-hydroxypropyl-b-CD (HP-b-CD)] were incorporated into liposomes prepared by the ethanol injection method. A 4.6-fold increase of encapsulation efficiency was achieved for the liposome-Bar/ HP-b-CD complex (Bar/HP-b-CD/liposome) in comparison with the conventional Bar/liposome. The size of the Bar/HPb-CD/liposome was 87.76 ± 1.45 nm and the zeta potential was -35.02 ± 0.50 mV. In addition, the liposomes remained stable in liquid form at 4°C for at least 3 months. The Bar/HP-b-CD/liposome was evaluated for anti-cancer activity in hepatocarcinoma HepG2 and colon cancer C26 cells and showed comparable toxicity to that of plain Bar. In vivo studies in hepatic cancer xenografted nude mice model showed that Bar/HP-b-CD/liposome significantly inhibited tumor growth with a substantial increase in animal survival. In conclusion, the encapsulation of the Bar/HP-b-CD complex into liposomes could provide an alternative means for its potential use in cancer therapy.

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Section: Discussionmentioning

confidence: 98%

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

Qiu

Cai

Wang

et al. 2015

J Incl Phenom Macrocycl Chem

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“…PBS has a neutral pH (7.4), which imparts a net neutral surface charge to the LNP. More extensive evaluations of LNP siRNA systems have been conducted by others (Crawford et al, 2011;Leung et al, 2012;Semple et al, 2001;Tam et al, 2013). These experiments have indicated that LNPs have an interior lipid core containing siRNA complexed with ionizable cationic lipids.…”

Section: Lipid Nanoparticlesmentioning

confidence: 99%

Self-Amplifying mRNA Vaccines

Brito

Kommareddy

Maione

et al. 2015

Advances in Genetics

151

168

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“…[18][19][20] LNP has been linked with bone formation and used for anabolic therapy, 16,21 but it has never been used in the treatment of cartilage diseases. Indeed, the LNP-siRNA system showed an exciting and promising silencing effect in vitro.…”

Section: Wang Et Almentioning

confidence: 99%

A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

Wei

Sun

Chen

et al. 2018

IJN

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Background Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog ( Ihh ) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). Results In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. Conclusion This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes.

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Analysis of lipid nanoparticles by Cryo-EM for characterizing siRNA delivery vehicles

Cited by 69 publications

References 21 publications

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

Self-Amplifying mRNA Vaccines

A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

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