Starburst low‐molecular weight polyethylenimine for efficient gene delivery

Zhao, Yanjun; Yang, Rulei; Liu, Dong; Sun, Meng; Zhou, Lijun; Zheng, Wang; Wan, Ying

doi:10.1002/jbm.a.33250

Cited by 16 publications

(9 citation statements)

References 29 publications

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“…The non-observed toxicity of star-shaped FA-CD-PLLD could be attributed to its lower molecular weight (less than 5 KDa) and the characteristic of molecular structure, such as the biodegradability and carrying a positive charge only on the surface. The biodegradability of FA-CD-PLLD can also promote its elimination from organism and thereby enhance the in vivo biocompatibility [35]. …”

Section: Discussionmentioning

confidence: 99%

Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

Liu

Wang

et al. 2016

Oncotarget

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The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.

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Section: Discussionmentioning

confidence: 99%

Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

Liu

Wang

et al. 2016

Oncotarget

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“…After grafted with PEI 1800 arms, the star‐shaped SCP‐based polyplexes had two orders of magnitude higher than DNA/PEI 1800 polyplexes, which was ascribed to the higher molecular weight by the grafting arms. Interestingly, PEGylation via host–guest interactions did not decrease the transfection efficiency, which was related to the star‐shaped architecture of polycations . It was also reported that PEGylation based PAMAM dendrimers could increase the transfection efficiency dendrimers .…”

Section: Resultsmentioning

confidence: 84%

Development of Supramolecular Pseudo‐Block Conjugates Based on Star‐Shaped Polycation for DNA Delivery

Kong

Mao

et al. 2015

Macro Chemistry & Physics

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Supramolecular assembly provides a new strategy for designing various gene carriers for deoxyribonucleic acid (DNA) delivery. In this work, supramolecular pseudo‐block conjugates based on star‐shaped polycation are developed as novel nonviral gene vector. First, cyclodextrin (CD) is selected as core and grafted with low molecular weight polyethylenimine (PEI1800) as arms to obtain high molecular weight star‐shaped polycation CD‐PEI8 (SCP). Then, azobenzene (Az) modified poly(ethylene glycol) is synthesized and named as azobenzene modified poly(ethylene glycol) (Az‐PEG). Subsequently, the supramolecular pseudo‐block conjugates are prepared via host–guest interaction between CD and Az. The result suggests that SCP/Az‐PEG condenses DNA into spherical nanoparticles with sizes of around 150 nm. The in vitro experiment shows that the cell viability of DNA/SCP/Az‐PEG polyplexes is significantly improved compared with that of PEI25k/DNA polyplexes. The PEGylation does not decrease the cellular uptake efficiency and transfection efficiency. Furthermore, the cellular trafficking shows that PEGylation does not significantly influence nuclear entry. The star‐shaped architecture of polycation plays an important role in gene delivery.

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“…Pluronic P123 with formula EO 20 -PO 70 -EO 20 , which has a proper hydrophile lipophilic balance (HLB) value, can be degraded to decrease cytotoxicity after cell uptake. Studies [10] showed that although the PEI derivate P123-PEI synthesized by cross-linking LMW-PEI with P123 had good degradability and low cytotoxicity, the transfection efficiency of the polymeric gene vector is not high enough.…”

Section: Introductionmentioning

confidence: 99%

Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA

Zhao

Liu

et al. 2016

Molecules

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Abstract:To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD) and a bifunctional R11 (RGD-NLS), which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100-280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18). More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector.

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Starburst low‐molecular weight polyethylenimine for efficient gene delivery

Cited by 16 publications

References 29 publications

Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

Development of Supramolecular Pseudo‐Block Conjugates Based on Star‐Shaped Polycation for DNA Delivery

Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA

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