Facile Synthesis of Multivalent Folate-Block Copolymer Conjugates via Aqueous RAFT Polymerization: Targeted Delivery of siRNA and Subsequent Gene Suppression

York, Adam W.; Zhang, Yilin; Holley, Andrew C.; Guo, Yan‐Lin; Huang, Faqing; McCormick, Charles L.

doi:10.1021/bm8014768

Cited by 107 publications

(132 citation statements)

References 61 publications

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“…The use of macro-RAFT agents as stabilizers in 'surfactantless' emulsion polymerization, [145,181,225,287,300,310,341,393,[443][444][445][446] miniemulsion polymerization, [124,181] suspension polymerization [381] and non-aqueous dispersion polymerization in both organic media, [188] and in supercritical CO 2 [353,389,447,448] [90,451] O O ϩ NH 3 Cl Ϫ APMAM 274 [152,153,168] Cl Ϫ O HN H 3 N ϩ AEMAM 275 [153] ϩ NH 3 Cl Ϫ O HN 276 [166] NH 3 Cl Ϫ O HN N N N ϩ has gained popularity. Particle nucleation and growth during RAFT emulsion polymerization of St and BA mediated by macro-RAFT agents of various compositions has been studied by calorimetry.…”

Section: Raft Polymerization In Heterogeneous Mediamentioning

confidence: 99%

“…It was reported that aminolysis of PNIPAM trithiocarbonate proceeds quantitatively to the thiol when conducted in the presence of a [370] MMA Ph (28) AIBN [173] MMA Ph (28) 393 [173] MMA C 10 H 7 (42) AIBN B [194] 416 Ph (25) ACVA C [164,474] DMAPMAM Ph (25) AIBN [168] NIPAM C 2 H 5 S (185) 394 [368] NIPAM C 2 H 5 S (189) 394 [374] NIPAM C 12 H 25 S (139) AIBN [324] NIPAM S(PDMAM-b-PNIPAM) (398) AIBN [475] DMAM S(PDMAM) (398) AIBN [475] NAM/NAS C 12 H 25 S (115) AIBN [299] St Ph (24) AIBN [133] St C 4 H 9 S (160) AIBN D [473] St Ph (50) 395 [476] St S(PSt) (398) AIBN [475] VAc small amount of a phosphine reducing agent (TCEP). [371,372] Two groups have compared aminolysis with borohydride reduction for PSt dithiobenzoate.…”

Section: Aminolysis/hydrolysis/ionic Reductionmentioning

confidence: 99%

See 1 more Smart Citation

Living Radical Polymerization by the RAFT Process - A Second Update

Moad¹,

Rizzardo²,

Thang³

2009

Aust. J. Chem.

905

720

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This paper provides a second update to the review of reversible deactivation radical polymerization achieved with thiocarbonylthio compounds (ZC(=S)SR) by a mechanism of reversible addition-fragmentation chain transfer (RAFT) that was published in June 2005 (Aust. J. Chem. 2005, 58, 379-410). The first update was published in November 2006 (Aust. J. Chem. 2006, 59, 669-692). This review cites over 500 papers that appeared during the period mid-2006 to mid-2009 covering various aspects of RAFT polymerization ranging from reagent synthesis and properties, kinetics and mechanism of polymerization, novel polymer syntheses and a diverse range of applications. Significant developments have occurred, particularly in the areas of novel RAFT agents, techniques for end-group removal and transformation, the production of micro/nanoparticles and modified surfaces, and biopolymer conjugates both for therapeutic and diagnostic applications.

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Section: Raft Polymerization In Heterogeneous Mediamentioning

confidence: 99%

Section: Aminolysis/hydrolysis/ionic Reductionmentioning

confidence: 99%

Living Radical Polymerization by the RAFT Process - A Second Update

Moad¹,

Rizzardo²,

Thang³

2009

Aust. J. Chem.

905

720

View full text Add to dashboard Cite

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“…29 As a synthetic technique, RAFT offers a convenient platform for molecular engineering of polymeric systems for drug delivery, biotechnology, nanotechnology and nanomedicine applications. [30][31][32][33][34][35][36][37] It has already been used to synthesise a range of polymeric structures for siRNA delivery, [38][39][40][41][42][43][44][45][46] with certain RAFT generated polymers found to have low levels of cytotoxicity. 47,48 In this study a novel polycationic system that is capable of selfassembly in aqueous solutions and of forming small, stable nanoparticles when complexed to siRNAs has been synthesized, imbuing nonviral carrier characteristics such as gene protection, phase transition and buffering capacity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, self-assembly and stimuli responsive properties of cholesterol conjugated polymers

et al. 2012

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Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to generate welldefined pH-responsive biofunctional polymers as potential 'smart' gene delivery systems. A series of five poly(dimethylamino ethyl methacrylate-co-cholesteryl methacrylate) P(DMAEMA-co-CMA) statistical copolymers, with similar molecular weights and varying cholesterol content, were prepared. The syntheses, compositions and molecular weight distributions for P(DMAEMA-co-CMA) were monitored by nuclear magnetic resonance (NMR), solid-state NMR and gel permeation chromatography (GPC) evidencing well-defined polymeric structures with narrow polydispersities. Aqueous solution properties of the copolymers were investigated using turbidimetry and light scattering to determine hydrodynamic diameters and zeta potentials associated with the phase transition behaviour of P(DMAEMA-co-CMA) copolymers. UV-Visible spectroscopy was used to investigate the pH-responsive behaviour of copolymers. Hydrodynamic radii were measured in the range 10-30 nm (pH, temperature dependent) by dynamic light scattering (DLS). Charge studies indicated that P(DMAEMA-co-CMA) polymers have an overall cationic charge, mediated by pH. Potentiometric studies revealed that the buffering capacity and pK a values of polymers were dependent on cholesterol content as well as on cationic charge. The buffering capacity increased with increasing charge ratio, overall demonstrating transitions in the pH endosomal region for all five copolymeric structures. Cell viability assay showed that the copolymers displayed increasing cytotoxicity with decreasing number of cholesterol moieties. These preliminary results show the potential of these welldefined P(DMAEMA-co-CMA) polymers as in vitro siRNA delivery agents.

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“…Recent advances in controlled radical polymerization (CRP) provide unprecedented control over monomer sequence 20,21 , chemical functionalities 22,23 and molecular weight distribution [24][25][26] . CRP has been extensively utilized for the synthesis of polymers suitable for biological applications such as nucleic acid delivery systems 25,[27][28][29][30][31][32][33][34] . Covalent and non-covalent RNA-polymer conjugation approaches have been described 35 .…”

Section: Introductionmentioning

confidence: 99%

Phosphonium Polymethacrylates for Short Interfering RNA Delivery: Effect of Polymer and RNA Structural Parameters on Polyplex Assembly and Gene Knockdown

et al. 2015

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(2015) Phosphonium polymethacrylates for siRNA delivery: effect of polymer and RNA structural parameters on polyplex assembly and gene knockdown. Biomacromolecules, 16 (11). pp. 3480-3490. ISSN 1525-7797 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/35894/1/Phosphonium%20Polymethacrylates%20for %20Short%20Interfering%20RNA%20Delivery%20-%20%20Effect%20of%20Polymer %20and%20RNA%20Structural%20Parameters%20on%20Polyplex%20Assembly%20and %20Gene%20Knockdown%20-%20AAM.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. ABSTRACT: Synthetic polymers containing quaternary phosphonium salts are an emerging class of materials for the delivery of oligo/polynucleotides. In this work, cationic phosphonium saltcontaining polymethacrylates -and their corresponding ammonium analogues-were synthesized by RAFT polymerization. Both the nature of the charged heteroatom (N vs. P) and the length of the spacer separating the cationic units along the polymer backbone (oxyethylene vs. trioxyethylene) were systematically varied. Polymers efficiently bound siRNA at N + /P -or P + /Pratios of 2 and above. At a 20:1 ratio, small polyplexes (Rh: 4-15 nm) suitable for cellular uptake were formed that displayed low cytotoxicity. Whilst siRNA polyplexes from both ammonium and phosphonium polymers were efficiently internalised by GFP-expressing 3T3 cells, no knockdown of GFP expression was observed. However, 65% Survivin gene knockdown was observed when short interfering RNA (siRNA) was replaced with novel, multimerised long interfering liRNA 2 (liRNA) in HeLa cells, demonstrating the importance of RNA macromolecular architecture on RNA-mediated gene silencing.

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Facile Synthesis of Multivalent Folate-Block Copolymer Conjugates via Aqueous RAFT Polymerization: Targeted Delivery of siRNA and Subsequent Gene Suppression

Cited by 107 publications

References 61 publications

Living Radical Polymerization by the RAFT Process - A Second Update

Living Radical Polymerization by the RAFT Process - A Second Update

Synthesis, self-assembly and stimuli responsive properties of cholesterol conjugated polymers

Phosphonium Polymethacrylates for Short Interfering RNA Delivery: Effect of Polymer and RNA Structural Parameters on Polyplex Assembly and Gene Knockdown

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