Enzyme-responsive destabilization of stabilized plasmid-lipid nanoparticles as an efficient gene delivery

Song, Su Jeong; Lee, Seulgi; Lu, Yan; Choi, Joon Sig

doi:10.1016/j.ejps.2016.05.024

Cited by 22 publications

(15 citation statements)

References 29 publications

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“…Song et al described cathepsin B‐responsive stabilized plasmid‐lipid particles (SPLPs) to overcome inefficient endosomal escape as a means to boost transfection efficiency . The introduction of enzymatically cleavable peptide linkers such as GFLG, that act as recognition sequences make these particles prone to degradation by the endo‐lysosomal enzyme, cathepsin B.…”

Section: Enzyme‐responsive Liposomesmentioning

confidence: 99%

Stimuli‐responsive liposomes for drug delivery

Lee

Thompson

2017

WIREs Nanomed Nanobiotechnol

371

190

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The ultimate goal of drug delivery is to increase the bioavailability and reduce the toxic side effects of the active pharmaceutical ingredient (API) by releasing at a specific site of action. In the case of antitumor therapy, association of the therapeutic agent with a carrier system can minimize damage to healthy, non-target tissues, while limit systemic release and promoting long circulation to enhance uptake at the cancerous site due to the enhanced permeation and retention effect (EPR). Stimuli-responsive systems have become a promising way to deliver and release payloads in a site-selective manner and carrier systems have been derived from a wide variety of materials, including inorganic nanoparticles, lipids, and polymers that have been imbued with stimuli-sensitive properties to accomplish triggered release. The unique features in the tumor microenvironment can serve as an endogenous stimulus (pH, redox potential, or unique enzymatic activity) or the locus of an applied external stimulus (heat or light) to trigger the controlled release of API. Triggered release is generally based on the principle of membrane destabilization from local defects within bilayer membranes to effect release of liposome-entrapped drugs. This review focuses on the literature appearing between November 2008–February 2016 that reports new developments in stimuli-sensitive liposomal drug delivery strategies using pH change, enzyme transformation, redox reactions, and photochemical mechanisms of activation.

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Section: Enzyme‐responsive Liposomesmentioning

confidence: 99%

Stimuli‐responsive liposomes for drug delivery

Lee

Thompson

2017

WIREs Nanomed Nanobiotechnol

371

190

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“…PEG-GLFG lipid was synthesized using Fmoc chemistry as the synthesis procedure shown in Figure 2 [ 16 ]. PEG - GLFG was analyzed using 1 H-NMR spectroscopy in a DMSO-d 6 solvent.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the PEG-GLGF lipid of the liposomes were recognized and hydrolyzed by cathepsin B owing to the presence of enzyme-specific GLFG peptide sequence, which induced the collapse of GLGF/Dox and the subsequent release of Dox. The results indicate that the ‘GLFG’ sequence of PEG-GLFG was cleaved by cathepsin B, which helped regulate the controlled release of the drug targeting specific cancer cells [ 16 , 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…PEG-GLFG was synthesized following Fmoc chemistry [ 16 ]. PEG was dissolved in DMF solvent with Fmoc-Gly-OH (4 eq), HOBt (4 eq), HBTU (4 eq), DIPEA (8 eq) and reacted for 16 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…It is overexpressed in several cancer cells types and is associated with cancer progression and metastasis [ 15 ]. As such, several studies have attempted to develop therapeutic strategies that target cancer cells expressing cathepsin B [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Cathepsin B-Responsive Liposomes for Controlled Anticancer Drug Delivery in Hep G2 Cells

et al. 2020

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In recent decades, several types of anticancer drugs that inhibit cancer cell growth and cause cell death have been developed for chemotherapeutic application. However, these agents are usually associated with side effects resulting from nonspecific delivery, which may induce cytotoxicity in healthy cells. To reduce the nonspecific delivery issue, nanoparticles have been successfully used for the delivery of anticancer drugs to specific target sites. In this study, a functional polymeric lipid, PEG-GLFG-K(C16)2 (PEG-GLFG, polyethylene glycol-Gly-Leu-Phe-Gly-Lys(C16)2), was synthesized to enable controlled anticancer drug delivery using cathepsin B enzyme-responsive liposomes. The liposomes composed of PEG-GLFG/DOTAP (1,2-dioleoyl-3-trimethylammonium-propane (chloride salt))/DPPC (dipalmitoylphosphatidylcholine)/cholesterol were prepared and characterized at various ratios. The GLFG liposomes formed were stable liposomes and were degraded when acted upon by cathepsin B enzyme. Doxorubicin (Dox) loaded GLFG liposomes (GLFG/Dox) were observed to exert an effective anticancer effect on Hep G2 cells in vitro and inhibit cancer cell proliferation in a zebrafish model.

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Nanointerventions for Gene Therapy

Maheswari

Annenkov

2018

Gene and Cell Therapy: Biology and Applications

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Enzyme-responsive destabilization of stabilized plasmid-lipid nanoparticles as an efficient gene delivery

Cited by 22 publications

References 29 publications

Stimuli‐responsive liposomes for drug delivery

Stimuli‐responsive liposomes for drug delivery

Cathepsin B-Responsive Liposomes for Controlled Anticancer Drug Delivery in Hep G2 Cells

Nanointerventions for Gene Therapy

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