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Journal ArticleDOI: 10.1021/ACS.LANGMUIR.0C02197

Mixed Polyplex Micelles with Thermoresponsive and Lysine-Based Zwitterionic Shells Derived from Two Poly(vinyl amine)-Based Block Copolymers.

02 Mar 2021-Langmuir (American Chemical Society (ACS))-Vol. 37, Iss: 10, pp 3001-3014
Abstract: Two series of poly(vinyl amine) (PVAm)-based block copolymers with zwitterionic and thermoresponsive segments were synthesized by the reversible addition-fragmentation chain transfer polymerization. A mixture of the two copolymers, poly(N-acryloyl-l-lysine) (PALysOH) and poly(N-isopropylacrylamide) (PNIPAM), which have the same cationic PVAm chain but different shell-forming segments, were used to prepare mixed polyplex micelles with DNA. Both PVAm-b-PALysOH and PVAm-b-PNIPAM showed low cytotoxicity, with characteristic assembled structures and stimuli-responsive properties. The cationic PVAm segment in both block copolymers showed site-specific interactions with DNA, which were evaluated by dynamic light scattering, zeta potential, circular dichroism, agarose gel electrophoresis, atomic force microscopy, and transmission electron microscopy measurements. The PVAm-b-PNIPAM/DNA polyplexes showed the characteristic temperature-induced formation of assembled structures in which the polyplex size, surface charge, chiroptical property of DNA, and polymer-DNA binding were governed by the nitrogen/phosphate (N/P) ratio. The DNA binding strength and colloidal stability of the PVAm-b-PALysOH/DNA polyplexes could be tuned by introducing an appropriate amount of zwitterionic PALysOH functionality, while maintaining the polyplex size, surface charge, and chiroptical property, regardless of the N/P ratio. The mixed polyplex micelles showed temperature-induced stability originating from the hydrophobic (dehydrated) PNIPAM chains upon heating, and remarkable stability under salty conditions owing to the presence of the zwitterionic PALysOH chain on the polyplex surface.

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Topics: Micelle (52%), Cationic polymerization (51%), Chain transfer (50%) ... show more
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5 results found



Journal ArticleDOI: 10.1016/J.EURPOLYMJ.2021.110575
Abstract: We investigate the complexation ability of CH3I quaternized HOOC-poly(N-isopropylacrylamide)-b-poly(2-(dimethylamino) acrylate)-C12H25 (HOOC-PNIPAM-b-QPDMAEA-C12H25) thermoresponsive-cationic diblock copolymers, having different composition of the blocks, with linear DNA molecules of different lengths. The thermoresponsive-cationic diblock copolymers are able to self-assemble into nanosized aggregates in aqueous media, where the PNIPAM block possesses the inner part and the QPDMAEA block constitutes the outer part, even at ambient temperature (temperature below the LCST value of PNIPAM block) because of the presence of hydrophobic C12H25 groups placed at the QPDMAEA free chain end. Thermoresponive-cationic copolymer/DNA polyplexes were prepared at various N/P (amine over phosphate groups) ratios utilizing two DNAs of different lengths (DNAshort ≈ 113 bp and DNAlong ≈ 2000 bp). Fluorescence measurements of ethidium bromide quenching as well as UV–vis measurements reveal the complexation of the cationic polymeric aggregates with DNA molecules. In addition, dynamic and electrophoretic light scattering measurements show the structural features and the surface charge of the formed polyplexes at both 25 °C and 45 °C (temperature above the LCST value of PNIPAM block). The salt tolerance of the formed polyplexes was also examined by dynamic light measurements. The overall physiochemical characterization of the polyplexes provides new insights into the parameters affecting the interactions between thermoresponsive-cationic polymer aggregates and nucleic acids.

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1 Citations


Open accessJournal ArticleDOI: 10.3390/POLYM13142361
19 Jul 2021-Polymers
Abstract: In this work, the ability of thermo-responsive poly [butyl acrylate-b-N-isopropylacrylamide-b-2-(dimethylamino) ethyl acrylate] (PnBA-b-PNIPAM-b-PDMAEA) triblock terpolymer self-assemblies, as well as of their quaternized analogs (PnBA-b-PNIPAM-b-QPDMAEA), to form polyplexes with DNA through electrostatic interactions was examined. Terpolymer/DNA polyplexes were prepared in three different amine over phosphate group ratios (N/P), and linear DNA with a 2000 base pair length was used. In aqueous solutions, the terpolymers formed aggregates of micelles with mixed PNIPAM/(Q)PDMAEA coronas and PnBA cores. The PnBA-b-PNIPAM-b-PDMAEA terpolymers’ micellar aggregates were also examined as carriers for the model hydrophobic drug curcumin (CUR). The complexation ability of the terpolymer with DNA was studied by UV–Vis spectroscopy and fluorescence spectroscopy by investigating ethidium bromide quenching. Fluorescence was also used for the determination of the intrinsic fluorescence of the CUR-loaded micellar aggregates. The structural characteristics of the polyplexes and the CUR-loaded aggregates were investigated by dynamic and electrophoretic light scattering techniques. Polyplexes were found to structurally respond to changes in solution temperature and ionic strength, while the intrinsic fluorescence of encapsulated CUR was increased at temperatures above ambient.

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Open accessJournal ArticleDOI: 10.3389/FBIOE.2021.744657
Abstract: Natural amino acids and their derivatives are excellent building blocks of polymers for various biomedical applications owing to the non-toxicity, biocompatibility, and ease of multifunctionalization. In the present review, we summarized the common approaches to designing and constructing functional polymeric micelles based on basic amino acids including lysine, histidine, and arginine and highlighted their applications as drug carriers for cancer therapy. Different polypeptide architectures including linear polypeptides and dendrimers were developed for efficient drug loading and delivery. Besides, polylysine- and polyhistidine-based micelles could enable pH-responsive drug release, and polyarginine can realize enhanced membrane penetration and gas therapy by generating metabolites of nitric oxide (NO). It is worth mentioning that according to the structural or functional characteristics of basic amino acids and their derivatives, key points for designing functional micelles with excellent drug delivery efficiency are importantly elaborated in order to pave the way for exploring micelles based on basic amino acids.

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Topics: Drug carrier (57%), Drug delivery (55%), Polylysine (51%)

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83 results found


Journal ArticleDOI: 10.1021/CR800409E
Meredith A. Mintzer1, Eric E. Simanek1Institutions (1)
01 Feb 2009-Chemical Reviews
Abstract: The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less

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Topics: Gene delivery (55%)

2,048 Citations



Journal ArticleDOI: 10.1078/0171-9335-00363
Swaroop Mishra1, Paul Webster2, Mark E. Davis1Institutions (2)
Abstract: In vitro studies of non-viral gene delivery vectors are typically not performed at physiological conditions, and thus may not provide meaningful results for in vivo investigations. We determine if polycation-plasmid DNA complexes (polyplexes) exploited for in vitro studies behave similarly to variants more applicable to in vivo use by examining their cellular uptake and trafficking. Branched polyethylenimine (25 kDa) or a linear beta-cyclodextrin-containing polymer are each used to formulate polyplexes, which can be PEGylated (PEG: poly(ethylene glycol)) to create particles stable in physiological salt concentrations. Particle size, cellular uptake, intracellular trafficking, and reporter gene expression are reported for polyplexes and for their PEGylated variants. PEGylation confers salt stability to particles but produced a reduction in luciferase expression. Examination of in vitro particle internalization by transmission electron microscopy shows unmodified polyplexes entering cells as large aggregates while PEGylated particles remain small and discrete, both outside and within cells. Unmodified and PEGylated particles enter cells through the endocytic pathway and accumulate in a perinuclear region. Immunolabeling reveals unpackaged exogenous DNA in the cytoplasm and nuclei. It appears all particle types traffic towards the nucleus within vesicles and undergo degradation in vesicles and/or cytoplasm, and eventually some exogenous DNA enters the nucleus, where it is transcribed. In comparing polyplexes and their PEGylated variants, significant differences in particle morphology, cellular uptake, and resultant expression suggest that in vitro studies should be conducted with particles prepared for physiological conditions if the results are to be relevant to in vivo performance.

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Topics: Gene delivery (54%), PEGylation (53%)

644 Citations


Journal ArticleDOI: 10.1016/J.PROGPOLYMSCI.2009.05.002
Abstract: Amphiphilic copolymers are well developed as precursors for the preparation of micellar drug carriers. Poly( N -isopropylacrylamide) (PNIPAAm) is one of the most extensively studied thermo-sensitive polymers that exhibits a lower critical solution temperature (LCST) at around 33 °C in aqueous solution. Over the past decade, considerable efforts have been devoted to design and preparation of PNIPAAm-based thermo-sensitive polymeric micelles as delivery vehicles for controlled drug release. Present review highlights the recent developments in this field, and focuses on two categories of PNIPAAm-based copolymer micelles as smart drug delivery systems, i.e. micelles with PNIPAAm as hydrophilic shell-forming segments below the LCST and micelles with PNIPAAm as hydrophobic core-forming segments above the LCST.

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602 Citations


Journal ArticleDOI: 10.1021/MA020883+
15 Mar 2003-Macromolecules
Abstract: Free-radical polymerization in the presence of suitable addition−fragmentation chain transfer agents [SC(Z)S−R] (RAFT agents) possess the characteristics of a living polymerization (i.e., polymer products can be reactivated for chain extension and/or block synthesis, molecular weights are predetermined by RAFT agent concentration and conversion, narrow polydispersities are possible). Styrene polymerizations (110 °C, thermal initiation) were performed for two series of RAFT agents [SC(Z)S−CH2Ph and SC(Z)S−C(Me)2CN]. The chain transfer coefficients decrease in the series where Z is Ph > SCH2Ph ∼ SMe ∼ Me ∼ N-pyrrolo ≫ OC6F5 > N-lactam > OC6H5 > O(alkyl) ≫ N(alkyl)2 (only the first five in this series provide narrow polydispersity polystyrene ( trithiocarbonates ∼ dithioalkanoates > dithiocarbonates (xanthates) > dithiocarbamates. However, electron-withdrawing substituents on Z can enhance the...

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561 Citations