Factors influencing the transfection efficiency and cellular uptake mechanisms of Pluronic P123-modified polypropyleneimine/pDNA polyplexes in multidrug resistant breast cancer cells

Gu, Jijin; Hao, Junguo; Fang, Xiaoling; Sha, Xianyi

doi:10.1016/j.colsurfb.2015.12.023

Cited by 22 publications

(17 citation statements)

References 43 publications

(49 reference statements)

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“…In this study, the effect of serum on the transfection efficiency of RHB/pDNA and HA/RHB/pDNA nanoassemblies was investigated in B16F10 cells in the presence of different concentrations of serum (0%, 10%, 20%, and 40% FBS) (Figure ). In agreement with studies by other groups on polycation/pDNA, , in the presence of serum, the transfection efficiency of RHB/pDNA nanoassemblies and Lipofectamine 2000/pDNA complexes drastically suppressed even with 10% (v/v) of FBS. In contrast, fluorescence images of B16F10 cells which transfected with HA/RHB/pDNA nanoassemblies showed significantly higher fluorescence intensity in comparison with RHB/pDNA nanoassemblies in the presence of serum, suggesting that HA/RHB/pDNA nanoassemblies expressed much more GFP than RHB/pDNA nanoassemblies, and also indicating that serum attenuated slightly the transfection efficiency of the HA/RHB/pDNA nanoassemblies.…”

Section: Results and Discussionsupporting

confidence: 92%

“…It is well-known that endosome/lysosome system is the major challenge for efficient gene delivery. Endosomal/lysosomal escape based on the “proton sponge effect” is crucial to enhance the efficacy of gene delivery systems. , To investigate the intracellular distribution and localization of HA/RHB/pDNA nanoassemblies after cellular uptake, confocal laser scanning microscopy was used to collect images of the cells incubated with nanoassemblies for different time durations. As shown in Figure , a large amount of green fluorescence could be observed at all the time points tested in this study.…”

Section: Results and Discussionmentioning

confidence: 99%

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CD44-Targeted Hyaluronic Acid-Coated Redox-Responsive Hyperbranched Poly(amido amine)/Plasmid DNA Ternary Nanoassemblies for Efficient Gene Delivery

Chen

Ren

et al. 2016

Bioconjugate Chem.

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Hyaluronic acid (HA), which can specifically bind to CD44 receptor, is a specific ligand for targeting to CD44-overexpressing cancer cells. The current study aimed to develop ternary nanoassemblies based on HA-coating for targeted gene delivery to CD44-positive tumors. A novel reducible hyperbranched poly(amido amine) (RHB) was assembled with plasmid DNA (pDNA) to form RHB/pDNA nanoassemblies. HA/RHB/pDNA nanoassemblies were fabricated by coating HA on the surface of the RHB/pDNA nanoassembly core through electrostatic interaction. After optimization, HA/RHB/pDNA nanoassemblies were spherical, core-shell nanoparticles with nanosize (187.6 ± 11.4 nm) and negative charge (-9.1 ± 0.3 mV). The ternary nanoassemblies could efficiently protect the condensed pDNA from enzymatic degradation by DNase I, and HA could significantly improve the stability of nanoassemblies in the sodium heparin solution or serum in vitro. As expected, HA significantly decreased the cytotoxicity of RHB/pDNA nanoassemblies due to the negative surface charges. Moreover, it revealed that HA/RHB/pDNA nanoassemblies showed higher transfection activity than RHB/pDNA nanoassemblies in B16F10 cells, especially in the presence of serum in vitro. Because of the active recognition between HA and CD44 receptor, there was significantly different transfection efficiency between B16F10 (CD44+) and NIH3T3 (CD44-) cells after treatment with HA/RHB/pDNA nanoassemblies. In addition, the cellular targeting and transfection activity of HA/RHB/pDNA nanoassemblies were further evaluated in vivo. The results indicated that the interaction between HA and CD44 receptor dramatically improved the accumulation of HA/RHB/pDNA nanoassemblies in CD44-positive tumor, leading to higher gene expression than RHB/pDNA nanoassemblies. Therefore, HA/RHB/pDNA ternary nanoassemblies may be a potential gene vector for delivery of therapeutic genes to treat CD44-overexpressing tumors in vivo.

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Section: Results and Discussionsupporting

confidence: 92%

Section: Results and Discussionmentioning

confidence: 99%

CD44-Targeted Hyaluronic Acid-Coated Redox-Responsive Hyperbranched Poly(amido amine)/Plasmid DNA Ternary Nanoassemblies for Efficient Gene Delivery

Chen

Ren

et al. 2016

Bioconjugate Chem.

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“…OHA NPs were prepared according to the method described by Duceppe and Tabrizian [37]. In brief, 5 mg HA was dissolved in 2 ml of distilled water under magnetic stirring.…”

Section: Ocmcs-ha/aera (Oha) Npsmentioning

confidence: 99%

Nano-polyplex based on oleoyl-carboxymethy-chitosan (OCMCS) and hyaluronic acid for oral gene vaccine delivery

Liu

Wang

Shah

et al. 2016

Colloids and Surfaces B: Biointerfaces

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Here we described nano-polyplexes (NPs) made of oleoyl-carboxymethy-chitosan (OCMCS)/hyaluronic acid (HA) as novel potential carriers for oral gene vaccines delivery. Aerolysin gene (aerA) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS-HA/aerA (OHA) NPs. OHA NPs performed the optimal parameters, i.e. smallest (154.5±9.4nm), positive charged (+7.9±0.5mV) and monodispersed system with the N/P ratio of 5 and OCMCS/HA weight ratio of 4. Upon the introduction of HA, OHA NPs was beneficial for the DNA release in intestinal environments in comparison to OA NPs. The mean fluorescence intensity detected in Caco-2 cells incubated with OHA NPs was about 2.5-fold higher than that of OA NPs; however, it decreased significantly in the presence of excess free HA. The OHA NPs and OA NPs decreased the transepithelial electric resistance (TEER) of Caco-2 monolayers obviously and induced increasing the apparent permeability coefficient (Papp) of DNA by 5.45-6.09 folds compared with free DNA. Significantly higher (P<0.05) antigen-specific antibodies were detected in serum after orally immunized with OHA NPs than that immunized with OA NPs and DNA alone in carps. These results enable the OHA NPs might resolve challenges arising from gastrointestinal damage to gene antigens, and offer an approach applicable for oral vaccination.

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“…Here, biological activities were improved; for example after alkylcarboxylation of G4 PPI with 10-bromodeconoic acid or fluorination of G3-G5 PPIs with heptafluorobutyric acid [39,40]. Other studies explored PPI copolymers like PPI-poly-L-lysine, PPI-oligoethylenimine or PPI-Pluronic ® P123 [33,41,42]. Smaller molecules were found to be efficient as well.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine-Modification of Polypropylenimine (PPI) and Polyethylenimine (PEI) Strongly Improves Efficacy of siRNA-Mediated Gene Knockdown

et al. 2020

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The delivery of small interfering RNAs (siRNA) is an efficient method for gene silencing through the induction of RNA interference (RNAi). It critically relies, however, on efficient vehicles for siRNA formulation, for transfection in vitro as well as for their potential use in vivo. While polyethylenimines (PEIs) are among the most studied cationic polymers for nucleic acid delivery including small RNA molecules, polypropylenimines (PPIs) have been explored to a lesser extent. Previous studies have shown the benefit of the modification of small PEIs by tyrosine grafting which are featured in this paper. Additionally, we have now extended this approach towards PPIs, presenting tyrosine-modified PPIs (named PPI-Y) for the first time. In this study, we describe the marked improvement of PPI upon its tyrosine modification, leading to enhanced siRNA complexation, complex stability, siRNA delivery, knockdown efficacy and biocompatibility. Results of PPI-Y/siRNA complexes are also compared with data based on tyrosine-modified linear or branched PEIs (LPxY or PxY). Taken together, this establishes tyrosine-modified PPIs or PEIs as particularly promising polymeric systems for siRNA formulation and delivery.

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Factors influencing the transfection efficiency and cellular uptake mechanisms of Pluronic P123-modified polypropyleneimine/pDNA polyplexes in multidrug resistant breast cancer cells

Cited by 22 publications

References 43 publications

CD44-Targeted Hyaluronic Acid-Coated Redox-Responsive Hyperbranched Poly(amido amine)/Plasmid DNA Ternary Nanoassemblies for Efficient Gene Delivery

CD44-Targeted Hyaluronic Acid-Coated Redox-Responsive Hyperbranched Poly(amido amine)/Plasmid DNA Ternary Nanoassemblies for Efficient Gene Delivery

Nano-polyplex based on oleoyl-carboxymethy-chitosan (OCMCS) and hyaluronic acid for oral gene vaccine delivery

Tyrosine-Modification of Polypropylenimine (PPI) and Polyethylenimine (PEI) Strongly Improves Efficacy of siRNA-Mediated Gene Knockdown

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