In vivo activation of PEGylated long circulating lipid nanoparticle to achieve efficient siRNA delivery and target gene knock down in solid tumors

Sasayama, Yumi; Hasegawa, Maki; Taguchi, Eri; Kubota, Keiichi; Kuboyama, Takeshi; Naoi, Tomoyuki; Yabuuchi, Hayato; Shimai, Norie; Asano, M; Tokunaga, Akihiro; Ishii, Toshihiko; Enokizono, Junichi

doi:10.1016/j.jconrel.2019.09.004

Cited by 30 publications

(16 citation statements)

References 31 publications

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“…Many efforts have been made to avoid the negative effects of corona, among which PEGylation 44 , 45 is more effective and commonly used. Attaching PEG chains creates a shielding layer at the surface of CLs and hence the formation of steric barriers and the reduction of exposed charges, 46 resulting in less formation of PC and extension of circulation time in the body.…”

Section: Main Textmentioning

confidence: 99%

“…Importantly, however, note that the isolated serum or plasma is not completely consistent with the actual physiological environment, which means that in vitro experiments on liposomes cannot be fully used to predict their behavioral changes in vivo. 43 Many efforts have been made to avoid the negative effects of corona, among which PEGylation 44,45 is more effective and commonly used. Attaching PEG chains creates a shielding layer at the surface of CLs and hence the formation of steric barriers and the reduction of exposed charges, 46 resulting in less formation of PC and extension of circulation time in the body.…”

Section: The Extracellular Barriersmentioning

confidence: 99%

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Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy

Liu

Zhang

Zhu

et al. 2020

Molecular Therapy - Methods & Clinical Development

131

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Cationic liposomes (CLs) have been regarded as the most promising gene delivery vectors for decades with the advantages of excellent biodegradability, biocompatibility, and high nucleic acid encapsulation efficiency. However, the clinical use of CLs in cancer gene therapy is limited because of many uncertain factors in vivo . Extracellular barriers such as opsonization, rapid clearance by the reticuloendothelial system and poor tumor penetration, and intracellular barriers, including endosomal/lysosomal entrapped network and restricted diffusion to the nucleus, make CLs not the ideal vector for transferring extrinsic genes in the body. However, the obstacles in achieving productive therapeutic effects of nucleic acids can be addressed by tailoring the properties of CLs, which are influenced by lipid compositions and surface modification. This review focuses on the physiological barriers of CLs against cancer gene therapy and the effects of lipid compositions on governing transfection efficiency, and it briefly discusses the impacts of particle size, membrane charge density, and surface modification on the fate of CLs in vivo , which may provide guidance for their preclinical studies.

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Section: Main Textmentioning

confidence: 99%

Section: The Extracellular Barriersmentioning

confidence: 99%

Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy

Liu

Zhang

Zhu

et al. 2020

Molecular Therapy - Methods & Clinical Development

131

View full text Add to dashboard Cite

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“…At the same time, the reduction response characteristics and ‘proton pump effect’ of PSH were conducive to the disintegration of nanoparticles and the rapid release of siRNA into the cytoplasm (Yang et al, 2015 ). The long circulation characteristic of PEG-DSPE also played a certain role in the improvement of antitumor activity (Sasayama et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

cRGD peptide-conjugated polyethylenimine-based lipid nanoparticle for intracellular delivery of siRNA in hepatocarcinoma therapy

et al. 2021

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The effective delivery system plays an important role in the application of siRNA in the antitumor study. However, until now, researches on the delivery systems targeting hepatocarcinoma cells are still being explored. Here we designed and prepared a novel siRNA delivery system, cRGD-PSH-NP, which was based on a modified polyethyleneimine (PSH) and DSPE-PEG 2000 -cRGD. cRGD-PSH-NP loaded with survivin siRNA (cRGD-PSH-NP/S) was composed of egg phosphatidylcholine, cationic PSH, PEGylated lipids, survivin siRNA, and cRGD peptide as a targeting ligand. The formulations of cRGD-PSH-NP/S were optimized and characterized. In vitro investigations showed excellent gene silencing and antitumor activity compared with the unmodified nanoparticles in HepG2 cells. In vivo antitumor efficacy of cRGD-PSH-NP/S exhibited potent tumor inhibition (74.71%) in HepG2-bearing nude mice without inducing toxicity. These data suggested further research of cRGD-PSH-NP/S in hepatocarcinoma therapy.

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“…have employed cholesterol to develop a nanoparticle formulation LNPK15 based on 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-(poly-ethyleneglycol-2000). This formulation showed extended half-lives in mice and monkeys as 15.2 h and 27.0 h, respectively, and also exhibited potent knock-down efficiency ( 42 ).…”

Section: Methodsmentioning

confidence: 99%

Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects

Gao

2021

AAPS J

209

128

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Gene therapy has been experiencing a breakthrough in recent years, targeting various specific cell groups in numerous therapeutic areas. However, most recent clinical studies maintain the use of traditional viral vector systems, which are challenging to manufacture cost-effectively at a commercial scale. Non-viral vectors have been a fast-paced research topic in gene delivery, such as polymers, lipids, inorganic particles, and combinations of different types. Although non-viral vectors are low in their cytotoxicity, immunogenicity, and mutagenesis, attracting more and more researchers to explore the promising delivery system, they do not carry ideal characteristics and have faced critical challenges, including gene transfer efficiency, specificity, gene expression duration, and safety. This review covers the recent advancement in non-viral vectors research and formulation aspects, the challenges, and future perspectives.

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In vivo activation of PEGylated long circulating lipid nanoparticle to achieve efficient siRNA delivery and target gene knock down in solid tumors

Cited by 30 publications

References 31 publications

Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy

Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy

cRGD peptide-conjugated polyethylenimine-based lipid nanoparticle for intracellular delivery of siRNA in hepatocarcinoma therapy

Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects

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