Nano‐Sized Sunflower Polycations As Effective Gene Transfer Vehicles

Cheng, Yilong; Wei, Hua; Tan, James Kevin Y; Peeler, David J.; Maris, Don O.; Sellers, Drew L.; Horner, Philip J.; Pun, Suzie H.

doi:10.1002/smll.201502930

Cited by 47 publications

(48 citation statements)

References 42 publications

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“…Then, c ‐P(HEMA‐Br) and l ‐P(HEMA‐Br) were synthesized according to the esterification reaction . Briefly, c ‐PHEMA (0.200 g, 1.537 mmol of HEMA units) was dissolved in 5 mL of dry pyridine.…”

Section: Methodsmentioning

confidence: 99%

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery

Meng

Wang

et al. 2018

Macromol. Rapid Commun.

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Adaptation of cyclic brush polymer for drug delivery applications remains largely unexplored. Herein, cyclic brush copolymer of poly(2-hydroxyethyl methacrylate-g-poly(N-isopropylacrylamide-st-N-hydroxyethylacrylamide)) (cb-P(HEMA-g-P(NIPAAm-st-HEAAm))), comprising a cyclic core of PHEMA and thermosensitive brushes of statistical copolymer of P(NIPAAm-st-HEAAm), is designed and synthesized successfully via a graft-from approach using atom transfer free radical polymerization from a cyclic multimacroinitiator. The composition of the brush is optimized to endow the resulting cyclic brush copolymer with a lower critical solution temperature (LCST) slightly above the physiological temperature, but lower than the localized temperature of tumor tissue, which is suitable for the hyperthermia-triggered anticancer drug delivery. Critical aggregation concentration determination reveals better stability for the unimolecular nanoparticle formed by the cyclic brush copolymer than that formed by the bottlebrush analogue. The dramatically increased size with elevated temperatures from below to above the LCST confirms hyperthermia-induced aggregation for both formulations. Such structural destabilization promotes significantly the drug release at 40 °C. Most importantly, the drug-loaded cyclic brush copolymer shows enhanced in vitro cytotoxicity against HeLa cells than the bottlebrush counterpart. The better stability and higher therapeutic efficacy demonstrates that the thermosensitive cyclic brush copolymer is a better formulation than bottle brush copolymer for controlled drug release applications.

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Section: Methodsmentioning

confidence: 99%

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery

Meng

Wang

et al. 2018

Macromol. Rapid Commun.

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“…Third, polyplex unpackaging was evaluated by YOYO-1 assay under various conditions [32]. Ideal gene carriers should strongly condense pDNA avoiding undesired degradation before cellular uptake while also releasing the cargo intracellularly, e.g .…”

Section: Resultsmentioning

confidence: 99%

“…The injection procedure was followed as described before [32]. Different formulations were prepared in 5% glucose solution containing 2.5 mg of DNA at desired N/P.…”

Section: Methodsmentioning

confidence: 99%

Development of switchable polymers to address the dilemma of stability and cargo release in polycationic nucleic acid carriers

et al. 2017

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Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)–b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery.

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“…We first screened a panel of the following nonviral transfection reagents: VIPER, Lipofectamine, high-molecular weight branched polyethylenimine, cationic sunflower polymers (Cheng, Wei, et al, 2016), and the TransIT system for delivery of a 4.2 kilo-basepairs plasmid encoding for the reporter gene tdTomato. As VIPER outperformed all other transfection reagents in gene transfer efficiency ( Figure S1 A panel of VIPER variants with different membrane-lytic peptides was tested to identify the best-performing VIPER formulation.…”

Section: Optimization Of Nonviral Gene Deliverymentioning

confidence: 99%

Optimized nonviral gene delivery for primary urinary renal progenitor cells to enhance cell migration

Liu

Johnson

Jain

et al. 2019

J Biomedical Materials Res

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Progressive loss of glomerular podocytes during kidney disease leads to irreversible kidney failure, and is exacerbated by the fact that podocytes are terminally differentiated epithelial cells and unable to proliferate. Regeneration of lost podocytes must therefore derive from nonpodocyte sources. Human urine‐derived renal progenitor cells (uRPCs) are attractive podocyte progenitors for cell therapy applications due to their availability from patient urine and ability to migrate to injured glomeruli and differentiate into de novo podocytes after intravenous administration. Because gene delivery has emerged as an important strategy to augment the functionality and survival of cell therapies prior to injection, in this work we optimized nonviral gene delivery conditions (cell density, DNA dose, % FBS, and transfection material composition) to primary uRPCs. Using the cationic polymer‐peptide conjugate VIPER for gene delivery and the Sleeping Beauty transposon/transposase constructs for gene integration, we optimized transfection parameters to achieve efficient transgene expression (up to 55% transfected cells) and stable transgene expression (>65% integration efficiency) lasting up to 10 days. With these methods, we transfected uRPCs to overexpress CXCR4, an important chemokine receptor that mediates uRPC migration to the kidneys after intravenous injection, and demonstrate that CXCR4‐uRPCs exhibit enhanced migration compared to mock‐transfected cells.

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Nano‐Sized Sunflower Polycations As Effective Gene Transfer Vehicles

Cited by 47 publications

References 42 publications

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery

Development of switchable polymers to address the dilemma of stability and cargo release in polycationic nucleic acid carriers

Optimized nonviral gene delivery for primary urinary renal progenitor cells to enhance cell migration

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