PEGylated poly(amine-co-ester) micelles as biodegradable non-viral gene vectors with enhanced stability, reduced toxicity and higher in vivo transfection efficacy

Zhang, Xiaofang; Tang, Wenxin; Yang, Zhe; Luo, Xingen; Luo, Hongyu; Gao, Di; Chen, Ya; Jiang, Qing; Liu, Jie; Jiang, Zhaozhong

doi:10.1039/c4tb00439f

Cited by 34 publications

(54 citation statements)

References 46 publications

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“…6 ; Supplementary Table 1 ) 65 , 66 and fluorescence studies with pyrene-loaded trCLN3-L4 nanoconstructs (Supplementary Fig. 7 ; Supplementary Table 2 ) 67 . Both methods yielded CMC values in the range of 300–350 nM concentrations.…”

Section: Resultsmentioning

confidence: 99%

Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells

Prusty

Adam²,

Zadegan

et al. 2018

Nat Commun

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Platforms for targeted drug-delivery must simultaneously exhibit serum stability, efficient directed cell internalization, and triggered drug release. Here, using lipid-mediated self-assembly of aptamers, we combine multiple structural motifs into a single nanoconstruct that targets hepatocyte growth factor receptor (cMet). The nanocarrier consists of lipidated versions of a cMet-binding aptamer and a separate lipidated GC-rich DNA hairpin motif loaded with intercalated doxorubicin. Multiple 2′,6′-dimethylazobenzene moieties are incorporated into the doxorubicin-binding motif to trigger the release of the chemotherapeutics by photoisomerization. The lipidated DNA scaffolds self-assemble into spherical hybrid-nanoconstructs that specifically bind cMet. The combined features of the nanocarriers increase serum nuclease resistance, favor their import into cells presumably mediated by endocytosis, and allow selective photo-release of the chemotherapeutic into the targeted cells. cMet-expressing H1838 tumor cells specifically internalize drug-loaded nanoconstructs, and subsequent UV exposure enhances cell mortality. This modular approach thus paves the way for novel classes of powerful aptamer-based therapeutics.

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Section: Resultsmentioning

confidence: 99%

Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells

Prusty

Adam²,

Zadegan

et al. 2018

Nat Commun

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“…[12][13][14][15][16] Comprehensive reviews are available on enzymecatalyzed polyester syntheses via ring-opening polymerization of lactones, 17,18 polycondensation between diacids (or diesters) and diols, 19,20 polymerization of hydroxy acids, 19,21 and copolymerization of lactones with diesters and diols. Most recently, we have shown that Candida antarctica lipase B (CALB) is highly tolerant of tertiary amines and is an efficient catalyst for the synthesis of poly-(amine-co-esters) via copolymerization of diester with amino diol 27,28 or terpolymerization of lactone with diester and amino diol, [29][30][31] and for the preparation of poly(lactone-coβ-amino esters) from lactone and ω-hydroxy β-amino ester comonomers. Results so far demonstrate that enzymatic polymerization methods are capable of constructing multifunctional copolyesters from a variety of comonomers in one or a few reaction steps.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic synthesis of poly(ω-pentadecalactone-co-butylene-co-3,3′-dithiodipropionate) copolyesters and self-assembly of the PEGylated copolymer micelles as redox-responsive nanocarriers for doxorubicin delivery

Liu

Zhang

et al. 2015

Polym. Chem.

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Biodegradable copolyesters bearing disulfide functional groups in the main chain have been successfully synthesized by lipase-catalyzed copolymerization of lactone with disulfide-containing diester and diol. When poly(ethylene glycol) methyl ether (MeO-PEG-OH) was added as a chain terminating agent, the corresponding amphiphilic PEG-polyester block copolymers were formed. NMR analyses of the synthesized poly(ω-pentadecalactone-co-butylene-co-3,3'-dithiodipropionate) (PPBD) and PEG-PPBD copolymers indicate that the repeat unit distributions in PPBD chains or PPBD segments of PEG-PPBD chains are nearly statistically random. These new functional polyesters possess low toxicity and their hydrophobicity can be systematically adjusted by varying the lactone content in the polymers. In aqueous medium, the amphiphilic PEG-PPBD block copolymers self-assembled readily to form nanosized micelles that are capable of serving as efficient redox-responsive nanocarriers for anticancer drug delivery. The addition of D,L-dithiothreitol (DTT) reductant into the medium caused substantial swelling of the PEG-PPBD micelles and effectively triggered a fast drug release from the doxorubicin (DOX)-loaded micelles. Consistently, an in vitro cytotoxicity study revealed that the efficacy of DOX-loaded PEG-PPBD micelles against HepG2 cancer cells is enhanced by intracellular glutathione (GSH) after the internalization of the micelles by the cells. † These authors contributed equally to this work.

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“…An alternative method, the Gel Red (GR) dye exclusion assay, was utilized to confirm the gel retardation assay data in terms of the DNA binding ability of F1, F2, F6, and F7, and to gain more details on the DCF/DNA binding mechanism. In this method, GR, being sensitive, stable, and an environmentally safe fluorescent nucleic acid dye, was designed to replace the ethidium bromide for DNA staining [44]. The fluorescence of the GR significantly increases when dye molecules intercalate into double-stranded DNA, thus highest fluorescence signal is detected when the vector is absent or DNA is not interacting with the vector.…”

Section: Resultsmentioning

confidence: 99%

Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency

et al. 2019

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When studying polyethylenimine derivatives as nonviral vectors for gene delivery, among the important issues to be addressed are high toxicity, low transfection efficiency, and nucleic acid polyplex condensation. The molecular weight of polyethylenimine, PEGylation, biocompatibility and, also, supramolecular structure of potential carrier can all influence the nucleic acid condensation behavior, polyplex size, and transfection efficiency. The main challenge in building an efficient carrier is to find a correlation between the constituent components, as well as the synergy between them, to transport and to release, in a specific manner, different molecules of interest. In the present study, we investigated the synergy between components in dynamic combinatorial frameworks formed by connecting PEGylated squalene, poly-(ethyleneglycol)-bis(3-aminopropyl) and low molecular weight polyethylenimine components to 1,3,5-benzenetrialdehyde, via reversible imine bond, applying a dynamic combinatorial chemistry approach. We report comparative structural and morphological data, DNA binding affinity, toxicity and transfection efficiency concerning the ratio of polyethylenimine and presence or absence of poly-(ethyleneglycol)-bis(3-aminopropyl) in composition of dynamic combinatorial frameworks. In vitro biological assessments have revealed the fact that nonviral vectors containing poly-(ethyleneglycol)-bis(3-aminopropyl) and the lowest amount of polyethylenimine have significant transfection efficiency at N/P 50 ratio and display insignificant cytotoxicity on the HeLa cell line.

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PEGylated poly(amine-co-ester) micelles as biodegradable non-viral gene vectors with enhanced stability, reduced toxicity and higher in vivo transfection efficacy

Cited by 34 publications

References 46 publications

Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells

Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells

Enzymatic synthesis of poly(ω-pentadecalactone-co-butylene-co-3,3′-dithiodipropionate) copolyesters and self-assembly of the PEGylated copolymer micelles as redox-responsive nanocarriers for doxorubicin delivery

Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency

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