Self-assembly of poly(ethylene glycol-b-phenyl oxazoline) diblock copolymers in aqueous media and their interactions with proteins

Vlassi, Eleni; Papagiannopoulos, Aristeidis; Pispas, Stergios

doi:10.1007/s00396-017-4076-y

Cited by 8 publications

(14 citation statements)

References 44 publications

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“…No significant changes were either observed in the measured sizes and HPPhOx aggregate molar masses (Figure b). In our previous work with poly(ethylene glycol‐ b ‐phenyl oxazoline) diblock copolymers temperature dependence was observed . Disintegration of the formed aggregates was evident by LS in aqueous solutions.…”

Section: Resultsmentioning

confidence: 93%

“…Because of this relation to the structure of polypeptides they are recognized as pseudopeptides that may certainly find use in biotechnological applications . They have been synthesized by (living) cationic ring‐opening polymerization and their physicochemical properties are extensively studied in the form of homopolymers and copolymers . Several polyoxazolines have been described as smart bioinspired macromolecules with low toxicity …”

Section: Introductionmentioning

confidence: 99%

“…Hydrolyzed gradient oxazoline copolymers have utilized the complexation of ethylene imine groups with DNA while DNA capture and release from hydrogels has been explored with amine‐containing poly(2‐oxazoline) copolymers . Interactions with proteins have been investigated in solutions of poly(ethylene glycol)‐ b ‐poly(2‐phenyl‐2‐oxazoline) diblock copolymers and nanoengineered surfaces . Cationic poly(2‐oxazoline) with low protein binding has been proposed for targeted gene delivery .…”

Section: Introductionmentioning

confidence: 99%

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Hydrolyzed Poly(2‐plenyl‐2‐oxazoline)s in Aqueous Media and Biological Fluids

Vlassi

Papagiannopoulos

Pispas

2018

Macro Chemistry & Physics

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Hydrolyzed poly(2‐phenyl‐2‐oxazoline)s (PPhOx) are synthesized by partial hydrolysis of PPhOx in order to produce self‐assembling copolymers with chargeable and hydrophobic units. The resulting poly(ethylene imine‐co‐2‐phenyl‐2‐oxazoline) [P(EI‐co‐PhOx)] amphiphilic copolymers contain phenyl‐oxazoline and ethylene imine segments in a random sequence and their chemical structure is confirmed by 1H NMR and attenuated total reflection‐Fourier transform infrared spectroscopy. Static and dynamic light scattering experiments show that in aqueous solutions the random copolymers associate into aggregates of sizes in the range between 50 and 200 nm depending on the solution conditions and hydrophobic content. The positive charge of the nanoaggregates that is caused by protonation of the amine nitrogen is confirmed by zeta potential measurements. Self‐assembly in phosphate buffered saline results in large aggregates. The aggregates are proved to interact with fetal bovine serum proteins. This investigation shows that hydrolyzed phenyl oxazoline‐based copolymers provide stable amphiphilic nanoparticles able to interact with biological macromolecules for biotechnological and pharmaceutical applications.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hydrolyzed Poly(2‐plenyl‐2‐oxazoline)s in Aqueous Media and Biological Fluids

Vlassi

Papagiannopoulos

Pispas

2018

Macro Chemistry & Physics

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“…Despite this progress toward designing effective DDS, one of the crucial challenges in using self-assembled nanomaterials is their stability in the biological media, (e.g., blood and serum). When DDS are administrated intravenously, they encounter multiple biomolecular species that are present in the blood that can interact with the polymeric assemblies and affect their structure and functionality. , Serum proteins are known to adsorb onto nanocarriers forming a protein corona that affects the surface properties and behavior of the polymeric assemblies. − Moreover, serum proteins can prematurely disassemble the micelle and lead to nonselective release of the cargo in healthy tissues. These issues are often overlooked in the literature, most likely due to the difficulties of studying micellar assemblies in complex biological media.…”

Section: Introductionmentioning

confidence: 99%

Micellar Stability in Biological Media Dictates Internalization in Living Cells

et al. 2017

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The dynamic nature of polymeric assemblies makes their stability in biological media a crucial parameter for their potential use as drug delivery systems in vivo. Therefore, it is essential to study and understand the behavior of self-assembled nanocarriers under conditions that will be encountered in vivo such as extreme dilutions and interactions with blood proteins and cells. Herein, using a combination of fluorescence spectroscopy and microscopy, we studied four amphiphilic PEG-dendron hybrids and their self-assembled micelles in order to determine their structure-stability relations. The high molecular precision of the dendritic block enabled us to systematically tune the hydrophobicity and stability of the assembled micelles. Using micelles that change their fluorescent properties upon disassembly, we observed that serum proteins bind to and interact with the polymeric amphiphiles in both their assembled and monomeric states. These interactions strongly affected the stability and enzymatic degradation of the micelles. Finally, using spectrally resolved confocal imaging, we determined the relations between the stability of the polymeric assemblies in biological media and their cell entry. Our results highlight the important interplay between molecular structure, micellar stability, and cell internalization pathways, pinpointing the high sensitivity of stability-activity relations to minor structural changes and the crucial role that these relations play in designing effective polymeric nanostructures for biomedical applications.

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“…The positive charges on cationic polymers usually cause problems when applied in vivo due to rapid clearance by the reticuloendothelial system (RES). These polymers were usually modified with biocompatible units such as PEG 213 , polyglutamic acid 214 , and polysaccharides 215 , 216 to shield the positive charges and increase the complex stability in vivo 217 . PEGylated PLL containing a pH-responsive linker was reported for the delivery of RNP into tumor cells 218 .…”

Section: Materials For Rnp Deliverymentioning

confidence: 99%

Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing

Song¹,

Shen²,

Li³

et al. 2021

Theranostics

272

184

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CRISPR/Cas9 genome editing has gained rapidly increasing attentions in recent years, however, the translation of this biotechnology into therapy has been hindered by efficient delivery of CRISPR/Cas9 materials into target cells. Direct delivery of CRISPR/Cas9 system as a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA (sgRNA) has emerged as a powerful and widespread method for genome editing due to its advantages of transient genome editing and reduced off-target effects. In this review, we summarized the current Cas9 RNP delivery systems including physical approaches and synthetic carriers. The mechanisms and beneficial roles of these strategies in intracellular Cas9 RNP delivery were reviewed. Examples in the development of stimuli-responsive and targeted carriers for RNP delivery are highlighted. Finally, the challenges of current Cas9 RNP delivery systems and perspectives in rational design of next generation materials for this promising field will be discussed.

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Self-assembly of poly(ethylene glycol-b-phenyl oxazoline) diblock copolymers in aqueous media and their interactions with proteins

Cited by 8 publications

References 44 publications

Hydrolyzed Poly(2‐plenyl‐2‐oxazoline)s in Aqueous Media and Biological Fluids

Hydrolyzed Poly(2‐plenyl‐2‐oxazoline)s in Aqueous Media and Biological Fluids

Micellar Stability in Biological Media Dictates Internalization in Living Cells

Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing

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