Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga V.; Thaxton, C. Shad

doi:10.1021/nl1041947

Cited by 114 publications

(106 citation statements)

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“…It has been reported that 1.9 nm AuNP 47 and 15 nm AuNP coated with m-PEG did not produce any adverse effect in mice. 32 In vitro toxicity of 15 nm AuNP coated with 11-MUA, 33 HDL coated AuNP, 5 PEI capped 15 nm AuNP, 34 silica coated AuNP 16 and a 153 nm PEGylated gold nanoshells 48 are found to be cytocompatible in a range of cell lines and under a range of conditions. Another in vitro study reported that cetyltrimethylammonium bromide coated gold nanorods reduce the HeLa cell viability 21%, whereas for the case of polyelectrolytes (such as poly(diallyldimethylammonium chloride)–poly(4-styrenesulfonic acid) coated gold nanorods are cytocompatible.…”

Section: Discussionmentioning

confidence: 99%

Systematic in vitro toxicological screening of gold nanoparticles designed for nanomedicine applications

Naha

Chhour

Cormode

2015

Toxicology in Vitro

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Gold nanoparticles (AuNP) are increasingly being applied in the biomedical field as therapeutics, contrast agents, and in diagnostic systems, motivating investigations of their toxicity that might arise from accidental exposure. While other work has investigated the toxicological response to gold nanoparticles for industrial purposes, here we have surveyed formulations that have been developed for biomedical use, are in clinical trials or have been FDA-approved. The AuNP library tested contains a range of shapes, inculding spheres, rods and shells, that possess a range of coatings, such as silica, citrate, lipoprotein, polymaleic acid, polyethylene glycol, DNA and others. Good cytocompatibility for all formulations was observed after 1 hour of incubation. However after 24 hours exposure, a nanorod and a spherical DNA coated formulation resulted in toxicity. The coating material was the only factor that influenced toxicity. AuNP exposure seemed to have no effect on cell cytoskeleton deformation and cell spreading. Cell uptake, as measured by computed tomography and ICP-OES, as well as TEM images of cells, confirmed strong AuNP uptake for certain formulations, but there was no correlation with toxicity. No glove translocation occurred, therefore, nitrile gloves are an adequate safety precaution for working with the AuNP studied. In conclusion, the majority of AuNP formulations tested have very low adverse effects.

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Section: Discussionmentioning

confidence: 99%

Systematic in vitro toxicological screening of gold nanoparticles designed for nanomedicine applications

Naha

Chhour

Cormode

2015

Toxicology in Vitro

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“…McMahon et al fabricated an artificial high density lipoprotein nanoparticle using a 5nm gold nanoparticle template [97]. The gold nanoparticle was mixed with Apolipoprotein A-I which subsequently stabilized the lipid mix on the surface of the gold nanoparticle, forming a lipid layer.…”

Section: Lipid Nanoparticles Mediated On Deliverymentioning

confidence: 99%

“…The final particle with ONs loaded is around 30nm. The nanoparticle was used to deliver anti-miR210 ONs to the PC-3 cells and caused an 80% reduction in cellular miR-210 levels [97]. Since the nanoparticle has shown serum stability and its capacity to protect ONs despite the payload being attached to the surface of the carrier, it holds potential to deliver ONs to the liver because Apolipoprotein A-I is a natural ligand for hepatocytes.…”

Section: Lipid Nanoparticles Mediated On Deliverymentioning

confidence: 99%

Delivery of oligonucleotides with lipid nanoparticles

Wang

Miao

Satterlee

et al. 2015

Advanced Drug Delivery Reviews

164

119

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Since their inception in the 1980's, oligonucleotide-based (ON-based) therapeutics have been recognized as powerful tools that can treat a broad spectrum of diseases. The discoveries of novel regulatory methods of gene expression with diverse mechanisms of action are still driving the development of novel ON-based therapeutics. Difficulties in the delivery of this class of therapeutics hinder their in vivo applications, which forces drug delivery systems to be a prerequisite for clinical translation. This review discusses the strategy of using lipid nanoparticles as carriers to deliver therapeutic ONs to target cells in vitro and in vivo. A discourse on how chemical and physical properties of the lipid materials could be utilized during formulation and the resulting effects on delivery efficiency constitutes the major part of this review.

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“…Green pharmaceutics aims at designing products and processes that significantly eliminate the use and generation of hazardous substances and prevent health impacts at source [24]. Nowadays, existing lipoprotein-based delivery platforms have so far been confined to single lipoprotein-like nanoparticles, such as conventionally reconstituted LDL (rLDL) [25] or reconstituted HDL (rHDL) [26], which were fabricated from isolated apolipoproteins and exogenous lipids. By mimicking the configuration of endogenous native lipoproteins, these recombinant LDL or HDL vehicles are capable of being retained in the systemic circulation for an extended period of time, largely evading the reticuloendothelial cells in vivo, and targeting cancer receptors (LDLR, LRP or SR-BI) to certain extents for enhanced therapeutic outcomes [18,27].…”

Section: Introductionmentioning

confidence: 99%