pH-labile sheddable block copolymers by RAFT polymerization: Synthesis and potential use as siRNA conjugates

Sevimli, Sema; Bulmuş, Volga

doi:10.1016/j.eurpolymj.2013.03.036

Cited by 16 publications

(18 citation statements)

References 59 publications

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“…These groups can be found in the polymer main/side chain, in end group and/or in the junction of blocks as can be seen in Figure 4h. These bonds can be irreversibly broken down at suitable pH values [57][58][59][60]. As can be seen in Figure 4i, it occurs by attaching various agents as side groups to the polymer chain and breaking the bonds at the appropriate pH value [57][58][59][60].…”

Section: Ph-responsive Polymersmentioning

confidence: 99%

“…In the second strategy, the release of drug molecules occurs with the cleavage of covalent bonds between polymer and drug molecule by pH changes. The followings are commonly used in polymer structures as pH-labile bonds for later strategy (Figure 6); hydrazone [66][67][68][69][70][71], acetal/ketal [72][73][74][75], cis-acotinyl [76][77][78][79][80], imine [81][82][83] substituted trityl [84][85][86], orthoester [57,87], boranate ester [88][89][90], β-thiopropionate [62,91], and others [92,93]. Xu and co-workers have well presented the recent developments in the area of pH-responsive polymerdrug conjugates with various structures and architectures [94].…”

Section: Ph-responsive Polymersmentioning

confidence: 99%

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Stimuli-Responsive Polymers Providing New Opportunities for Various Applications

Koçak

Tuncer

Bütün

2020

Hacettepe Journal of Biology and Chemistry

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U yaranlara duyarlı polimerler, çevrelerindeki koşullarda küçük bir değişiklik olduğunda fiziksel veya kimyasal özelliklerini önemli ölçüde değiştirir. Koşullardaki değişikliklere bağlı olarak, bu tür kopolimerler kendiliğinden bir araya gelebilir ve çeşitli nanoboyutlu yapılar oluşturabilir. Bu tür polimerlerin farklı alanlarda önemli kullanımları vardır. Bu derlemede, çevreye duyarlı farklı polimerlerin mimarileri, duyarlılıklarına göre sınıflandırmaları ve çeşitli alanlardaki uygulamaları gibi temel konulardaki bazı güncel literatür raporlarının bir analizini sunuyoruz. Son yirmi yılda, biyoteknoloji, nanoteknoloji, kolloid ve yüzey bilimi, malzeme bilimi vb. dahil olmak üzere çeşitli uygulamalar için uygun uyarıcıya duyarlı yeni polimerlerin ve polimerik malzemelerin hazırlanmasına yönelik sentetik yöntemlerde ve stratejilerde büyük gelişmeler olmuştur. Çok geniş kapsamı olan bu polimer türünün okuyucular tarafından daha anlaşılır olabilmesi için genellikle temel kavramlar/konular şematize edilmiştir. Ayrıca, bu malzemelerin üretiminde izlenebilecek stratejiler yeter düzeyde verilmeye çalışılmıştır. Anahtar KelimelerUyarıya-duyarlı polimerler, kendi-kendine-düzenlenme, nanoyapılar, akıllı polimerler.

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Section: Ph-responsive Polymersmentioning

confidence: 99%

Section: Ph-responsive Polymersmentioning

confidence: 99%

Stimuli-Responsive Polymers Providing New Opportunities for Various Applications

Koçak

Tuncer

Bütün

2020

Hacettepe Journal of Biology and Chemistry

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“…A possible risk, however, of such reversible systems is bioaccumulation as re-self-assembly can occur Next to imines, hydrazides, hydrazones, orthoesters and oximes, ketals are of particular interest due to their non-cytotoxic nature. 43,44,45,46,47,48 Several pH-sensitive ketal-based polymeric structures have been reported (e.g. micelles and microparticles).…”

Section: Introductionmentioning

confidence: 99%

Degradable Ketal-Based Block Copolymer Nanoparticles for Anticancer Drug Delivery: A Systematic Evaluation

et al. 2014

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Low solubility of potent (anticancer) drugs is a major driving force for the development of noncytotoxic, stimuli-responsive nanocarriers, including systems based on amphiphilic block copolymers. In this regard, we investigated the potential of block copolymers based on 2-hydroxyethyl acrylate (HEA) and the acid-sensitive ketal-containing monomer (2,2-dimethyl-1,3-dioxolane-4-yl)methyl acrylate (DMDMA) to form responsive drug nanocarriers. Block copolymers were successfully synthesized by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization, in which we combined a hydrophilic poly(HEA)x block with a (responsive) hydrophobic poly(HEAm-co-DMDMAn)y copolymer block. The DMDMA content of the hydrophobic block was systematically varied to investigate the influence of polymer design on physicochemical properties and in vitro biological performance. We found that a DMDMA content higher than 11 mol % is required for self-assembly behavior in aqueous medium. All particles showed colloidal stability in PBS at 37 °C for at least 4 days, with sizes ranging from 23 to 338 nm, proportional to the block copolymer DMDMA content. Under acidic conditions, the nanoparticles decomposed into soluble unimers, of which the decomposition rate was inversely proportional to the block copolymer DMDMA content. Flow cytometry and confocal microscopy showed dose-dependent, active in vitro cellular uptake of the particles loaded with hydrophobic octadecyl rhodamine B chloride (R18). The block copolymers showed no intrinsic in vitro cytotoxicity, while loaded with paclitaxel (PTX), a significant decrease in cell viability was observed comparable or better than the two commercial PTX nanoformulations Abraxane and Genexol-PM at equal PTX dose. This systematic approach evaluated and showed the potential of these block copolymers as nanocarriers for hydrophobic drugs.

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“…As several groups have indicated, the labile bonds in endosomes or secondary lysosomes can efficiently reduce the cytotoxicity [ 20 , 21 , 22 , 23 ]; therefore, a labile linkage in endosomes or secondary lysosomes such as an acid labile linker has been introduced into the backbone of the cationic polymers. For example, Bulmus et al inserted an acid-labile acetal bond in a PEG-macro initiator and prepared a polymer by the reversible-addition fragmentation chain transfer (RAFT) polymerization [ 24 ]. Xing et al prepared ketal containing diacrylate and prepare the acid-labile branched polydiethylenetriamines to form the polyplex with siRNA [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Rapid-Onset, Acid-Labile Linkage Polyplex-Mixed Micellar System for Anticancer Therapy

Hung

Wen

et al. 2021

Polymers

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In the treatment of cancers, small interfering ribonucleic acids (siRNAs) are delivered into cells to inhibit the oncogenic protein’s expression; however, polyanions, hydrophilicity, and rapid degradations in blood, endosomal or secondary lysosomal degradation hamper clinal applications. In this study, we first synthesized and characterized two copolymers: methoxy poly(ethylene glycol)-b-poly(2-hydroxy methacrylate-ketal-pyridoxal) and methoxy poly(ethylene glycol)-b-poly(methacrylic acid-co-histidine). Afterwards, we assembled two polymers with the focal adhesion kinase (FAK) siRNA, forming polyplex-mixed micelles for the treatment of the human colon cancer cell line HCT116. In terms of the physiological condition, the cationic pyridoxal molecules that were conjugated on the copolymer with ketal bonds could electrostatically attract the siRNA. Additionally, the pyridoxal could form a hydrophobic core together with the hydrophobic deprotonated histidine molecules in the other copolymer and the hydrophilic polyethylene glycol (PEG) shell to protect the siRNA. In an acidic condition, the pyridoxal would be cleaved from the polymers due to the breakage of the ketal bonds and the histidine molecules can simultaneously be protonated, resulting in the endosome/lysosome escape effect. On the basis of our results, the two copolymers were successfully prepared and the pyridoxal derivatives were identified to be able to carry the siRNA and be cleavable by the copolymers in an acidic solution. Polyplex-mixed micelles were prepared, and the micellar structures were identified. The endosome escape behavior was observed using a confocal laser scanning microscopy (CLSM). The FAK expression was therefore reduced, and the cytotoxicity of siRNA toward human colon cancer cells was exhibited, rapidly in 24 h. This exceptional anticancer efficiency suggests the potential of the pH-sensitive polyplex-mixed micellar system in siRNA delivery.

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pH-labile sheddable block copolymers by RAFT polymerization: Synthesis and potential use as siRNA conjugates

Cited by 16 publications

References 59 publications

Stimuli-Responsive Polymers Providing New Opportunities for Various Applications

Stimuli-Responsive Polymers Providing New Opportunities for Various Applications

Degradable Ketal-Based Block Copolymer Nanoparticles for Anticancer Drug Delivery: A Systematic Evaluation

Development of a Rapid-Onset, Acid-Labile Linkage Polyplex-Mixed Micellar System for Anticancer Therapy

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