In-vitro and in-vivo difference in gene delivery by lithocholic acid-polyethyleneimine conjugate

Wang, Jianping; Meng, Fanfei; Kim, Bieong-Kil; Xue, Ke; Yeo, Yoon

doi:10.1016/j.biomaterials.2019.119296

Cited by 40 publications

(38 citation statements)

References 47 publications

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“…Most of the red DNA fluorescence still did not overlapped with the lysosomes’ green fluorescence, and some of the red DNA fluorescence co-located into cell nuclei and as shown in a 2 h video for the PEI-GA 0.75 /pDNA (Supplement Materials Video S1). As shown in Figure 8C, most of the nuclei localizations of the PEI-GA 0.75 / cy5 pLUCI and GL1 0.62 / cy5 pLUCI polyplexes were observed within 5 h, despite not being as rapid as some quaternary ammonium cationic vectors [56,57] in our laboratory. Meanwhile, for the PEI-GA 1.7 /pLUCI polyplex with lower transfection efficiency, almost no DNA red fluorescence was observed in the nucleus, suggesting that its rate-limiting steps during transfection is probably due to intracellular trafficking.…”

Section: Resultsmentioning

confidence: 89%

Glycyrrhizin Acid and Glycyrrhetinic Acid Modified Polyethyleneimine for Targeted DNA Delivery to Hepatocellular Carcinoma

Cao

Gao

Zhan

et al. 2019

IJMS

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In the last 2–3 decades, gene therapy represented a promising option for hepatocellular carcinoma (HCC) treatment. However, the design of safe and efficient gene delivery systems is still one of the major challenges that require solutions. In this study, we demonstrate a versatile method for covalent conjugation of glycyrrhizin acid (GL) or glycyrrhetinic acid (GA) to increase the transfection efficiency of Polyethyleneimine (PEI, Mw 1.8K) and improve their targeting abilities of hepatoma carcinoma cells. GA and GL targeting ligands were grafted to PEI via N-acylation, and we systematically investigated their biophysical properties, cytotoxicity, liver targeting and transfection efficiency, and endocytosis pathway trafficking. PEI-GA0.75, PEI-GL10.62 and PEI-GL20.65 conjugates caused significant increases in gene transfection efficiency and superior selectivity for HepG2 cells, with all three conjugates showing specific recognition of HepG2 cells by the free GA competition assay. The endocytosis inhibition and intracellular trafficking results indicated that PEI-GA0.75 and GL10.62 conjugates behaved similarly to SV40 virus, by proceeding via the caveolae- and clathrin-independent mediated endocytosis pathway and bypassing entry into lysosomes, with an energy independent manner, achieving their high transfection efficiencies. In the HepG2 intraperitoneal tumor model, PEI-GA0.75 and PEI-GL10.62 carrying the luciferase reporter gene gained high gene expression, suggesting potential use for in vivo application.

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Section: Resultsmentioning

confidence: 89%

Glycyrrhizin Acid and Glycyrrhetinic Acid Modified Polyethyleneimine for Targeted DNA Delivery to Hepatocellular Carcinoma

Cao

Gao

Zhan

et al. 2019

IJMS

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“…Unfortunately, PEI of high molecular weight did not show high transfection efficiency and also showed significant systemic toxicity. To reduce the toxicity of a PEI-based delivery system, polyethyleneimine is most often combined with other polymers such as PEG [ 129 ] or dendrimers [ 130 ]. These have led to the successful clinical use of PEI to deliver sensitive genetic biomaterials [ 129 ].…”

Section: Targeting Tumor Tissues Via An Epr Effectmentioning

confidence: 99%

Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment

Subhan

Yalamarty

Filipczak

et al. 2021

JPM

280

150

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Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood vessels and remain at a high level in plasma. Over time, the concentration of nanodrugs builds up in tumors due to the EPR effect, reaching several times higher than that of plasma due to the lack of lymphatic drainage. This review will address in detail the progress and prospects of tumor-targeting via EPR effect for cancer therapy.

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“…To reduce the potential toxicity of PEI-based delivery system, PEI has been mixed with other polymers, especially PEG. These various efforts have led to the successful clinical application of PEI to deliver vulnerable genetic biomaterials 56. Similar to the azobenzene linker, 2-nitroimidazole has been widely utilized for hypoxia-sensitive drug delivery.…”

Section: Utilization Of Tme-specific Molecular Markersmentioning

confidence: 99%

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

et al. 2019

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The use of nanomedicine for cancer treatment takes advantage of its preferential accumulation in tumors owing to the enhanced permeability and retention (EPR) effect. The development of cancer nanomedicine has promised highly effective treatment options unprecedented by standard therapeutics. However, the therapeutic efficacy of passively targeted nanomedicine is not always satisfactory because it is largely influenced by the heterogeneity of the intensity of the EPR effect exhibited within a tumor, at different stages of a tumor, and among individual tumors. In addition, limited data on EPR effectiveness in human hinders further clinical translation of nanomedicine. This unsatisfactory therapeutic outcome in mice and humans necessitates novel approaches to improve the EPR effect. This review focuses on current attempts at overcoming the limitations of traditional EPR-dependent nanomedicine by incorporating supplementary strategies, such as additional molecular targeting, physical alteration, or physiological remodeling of the tumor microenvironment. This review will provide valuable insight to researchers who seek to overcome the limitations of relying on the EPR effect alone in cancer nanomedicine and go “beyond the EPR effect”.

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In-vitro and in-vivo difference in gene delivery by lithocholic acid-polyethyleneimine conjugate

Cited by 40 publications

References 47 publications

Glycyrrhizin Acid and Glycyrrhetinic Acid Modified Polyethyleneimine for Targeted DNA Delivery to Hepatocellular Carcinoma

Glycyrrhizin Acid and Glycyrrhetinic Acid Modified Polyethyleneimine for Targeted DNA Delivery to Hepatocellular Carcinoma

Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

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