Preparation and Characterization of Polyion Complex Micelles with Phosphobetaine Shells

Nakai, Keita; Nishiuchi, Midori; Inoue, Masamichi; Ishihara, Kazuhíko; Sanada, Yusuke; Sakurai, Kazuo; Yusa, Shin‐ichi

doi:10.1021/la401063b

Cited by 52 publications

(65 citation statements)

References 50 publications

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“…9,10,12 It is proposed that cationic block copolymers can condense pDNA with a core–shell structure. 33,34 The stabilization effect is likely attributed to the shell of PMAG, which serves as a bulky hydrophilic coating, preventing the polyplexes from aggregating in Opti-MEM. The protective function of the PMAG block that coats the polyplexes becomes apparent when comparing the stability of glycopolymer polyplexes with that of polyplexes formed with the cationic homopolymers.…”

Section: Resultsmentioning

confidence: 99%

Glucose-Containing Diblock Polycations Exhibit Molecular Weight, Charge, and Cell-Type Dependence for pDNA Delivery

Wang

Sprouse

et al. 2014

Biomacromolecules

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A series of diblock glycopolycations were created by polymerizing 2-deoxy-2-methacrylamido glucopyranose (MAG) with either a tertiary amine-containing monomer, N-[3-(N,N-dimethylamino) propyl] methacrylamide (DMAPMA), or a primary amine-containing unit, N-(2-aminoethyl) methacrylamide (AEMA). Seven structures were synthesized via aqueous reversible addition–fragmentation chain transfer (RAFT) polymerization that varied in the block lengths of MAG, DMAPMA, and AEMA along with two homopolymer controls of DMAPMA and AEMA that lacked a MAG block. The polymers were all able to complex plasmid DNA into polyplex structures and to prevent colloidal aggregation of polyplexes in physiological salt conditions. In vitro transfection experiments were performed in both HeLa (human cervix adenocarcinoma) cells and HepG2 (human liver hepatocellular carcinoma) cells to examine the role of charge type, block length, and cell type on transfection efficiency and toxicity. The glycopolycation vehicles with primary amine blocks and PAEMA homopolymers revealed much higher transfection efficiency and lower toxicity when compared to analogs created with DMAPMA. Block length was also shown to influence cellular delivery and toxicity; as the block length of DMAPMA increased in the glycopolycation-based polyplexes, toxicity increased while transfection decreased. While the charge block played a major role in delivery, the MAG block length did not affect these cellular parameters. Lastly, cell type played a major role in efficiency. These glycopolymers revealed higher cellular uptake and transfection efficiency in HepG2 cells than in HeLa cells, while homopolycations (PAEMA and PDMAPMA) lacking the MAG blocks exhibited the opposite trend, signifying that the MAG block could aid in hepatocyte transfection.

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Section: Resultsmentioning

confidence: 99%

Glucose-Containing Diblock Polycations Exhibit Molecular Weight, Charge, and Cell-Type Dependence for pDNA Delivery

Wang

Sprouse

et al. 2014

Biomacromolecules

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“…35 To obtain polymersomes rather than micelles the structure of the polymers, namely the ratio of the lengths of zwitterionic and charged blocks in the copolymers used, was adjusted accordingly. 35 To obtain polymersomes rather than micelles the structure of the polymers, namely the ratio of the lengths of zwitterionic and charged blocks in the copolymers used, was adjusted accordingly.…”

Section: Synthesis and Characterization Of Spion/ Cch-polymersomesmentioning

confidence: 99%

Stable polymersomes based on ionic–zwitterionic block copolymers modified with superparamagnetic iron oxide nanoparticles for biomedical applications

et al. 2015

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Stable polymersomes with semipermeable membranes were prepared by simple mixing of two oppositely charged diblock copolymers containing zwitterionic and cationic or anionic blocks. The formation of vesicular structures in the mixed solution of the block copolymers was confirmed by direct observation using the cryo-TEM technique. Superparamagnetic iron oxide nanoparticles coated with a cationic chitosan derivative (SPION/CCh) and decorated with a fluorescent probe molecule were next incorporated into the polymersome structure. The average diameter of SPION/CCh-polymersomes estimated using cryo-TEM was about 250 nm. Surface topography of the SPION/CCh-loaded vesicles was imaged using AFM and the magnetic properties of these objects were confirmed by MFM and MRI measurements. The ability of SPION/CCh-polymersomes to affect T 2 relaxation time in MRI was evaluated based on the measurements of r 2 relaxivity. The obtained value of r 2 (573 AE 10 mM À1 s À1 ) was quite high. The cytotoxicity and intracellular uptake of the SPION/CCh-loaded vesicles into EA.hy926 cells were studied. The results indicate that the SPION/CCh-polymersomes seem to be internalized by vascular endothelium and are not cytotoxic to endothelial cells up to 1 mg Fe per mL. Therefore, it can be suggested that SPION/CCh-polymersomes could prove useful as T 2 contrast agents in the MRI of endothelium.

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“…[19][20][21][22][23][24] Alternatively, there are also several reports on PIC micelle formation from block ionomers with hydrophilic segments other than PEG. [25][26][27] In this way, one can even place two different hydrophilic polymer strands into the same shell structure of a PIC micelle by selecting block aniomers and catiomers with different hydrophilic and non-ionic segments, as schematically shown in Figure 2. However, this situation is difficult if the hydrophilic polymer strands are inherently immiscible with each other, and this would be an interesting research subject to explore.…”

Section: Formation Of Pic Micelles From a Pair Of Oppositely Charged mentioning

confidence: 99%

Polyion complex micelle formation from double-hydrophilic block copolymers composed of charged and non-charged segments in aqueous media

Harada

Kataoka

2017

Polym J

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Polymeric micelles are representative self-assembly structures of block copolymers and have widely been investigated from both fundamental and applied aspects. In 1995, we discovered polyion complex (PIC) micelles formed from a pair of oppositely charged block copolymers with poly(ethylene glycol) segments through electrostatic interactions in aqueous media, which expanded the concept of polymeric micelle formation in selective solvents. Hereafter, extensive studies have been carried out on PIC micelles, for example, fundamental characterizations as a novel class of self-assembly systems and applications as nanocarrier systems for the delivery of charged molecules with therapeutic efficacies, including nucleic acids and proteins. This review mainly focuses on physicochemical studies on the formation of PIC micelles, particularly the critical molecular factors that have a role to determine the self-assembly scheme of charged block copolymers for micelle structures.

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Preparation and Characterization of Polyion Complex Micelles with Phosphobetaine Shells

Cited by 52 publications

References 50 publications

Glucose-Containing Diblock Polycations Exhibit Molecular Weight, Charge, and Cell-Type Dependence for pDNA Delivery

Glucose-Containing Diblock Polycations Exhibit Molecular Weight, Charge, and Cell-Type Dependence for pDNA Delivery

Stable polymersomes based on ionic–zwitterionic block copolymers modified with superparamagnetic iron oxide nanoparticles for biomedical applications

Polyion complex micelle formation from double-hydrophilic block copolymers composed of charged and non-charged segments in aqueous media

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