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A dual zwitterionic diblock copolymer (M100C100) consisting of poly(2‐(methacryloyloxy)ethyl phosphorylcholine) (PMPC, M) and poly(3‐((2‐(methacryloyloxy)ethyl) dimethylammonio) propionate) (PCBMA, C) is synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization. A double hydrophilic diblock copolymer (M100S100) consist of PMPC and anionic poly(3‐sulfopropyl methacrylate potassium salt) (PMPS, S) is synthesized via RAFT. The degrees of polymerization of each block are 100. The charges of PMPC are neutralized intramolecularly. At neutral pH, the charges in PCBMA are also neutralized intramolecularly due to its carboxybetaine structure. Under acidic conditions, PCBMA exhibits polycation behavior as the pendant carboxy groups become protonated, forming cationic tertiary amine groups. PMPS shows permanent anionic nature independent of pH. Charge neutralized mixture of cationic M100C100 and anionic M100S100 in acidic aqueous solution forms water‐soluble polyion complex (PIC) micelle owing to electrostatic attractive interactions. The core is composed of the cationic PCBMA and anionic PMPS blocks, with the PMPC blocks serving as shells that covered the core surface, forming spherical core–shell PIC micelles. Above pH 4 the pendant carboxy groups in PCBMA undergo deprotonation, transitioning to a zwitterionic state, thereby eliminating the cationic charge in PCBMA. Therefore, above pH 4 the PIC micelles are dissociated due to the disappearance of the charge interactions. [ABSTRACT FROM AUTHOR]

Trees grow by coupling the transpiration‐induced nutrient absorption from external sources and photosynthesis‐based nutrient integration. Inspired by this manner, we designed a class of polyion complex (PIC) hydrogels containing isolated liquid‐filled voids for growing texture surfaces. The isolated liquid‐filled voids were created via irreversible matrix reconfiguration in a deswelling‐swelling process. During transpiration, these voids reversibly collapse to generate negative pressures within the matrices to extract polymerizable compounds from external sources and deliver them to the surface of the samples for photopolymerization. This growth process is spatial‐controllable and can be applied to fabricate complex patterns consisting of different compositions, suggesting a new strategy for making texture surfaces. [ABSTRACT FROM AUTHOR]

Developing a novel approach for the administration of catechin that ensures sustained bioactivity, even at low doses, is crucial. In this regard, hydrogels were synthesized by polyion complexation of carboxymethyl cellulose (CMC) and chitosan (CS) grafted with epigallocatechin gallate (EGCG-g-CS), which can maintain enduring antioxidant activity. We initially synthesized grafted chitosan with various grafting ratios using a free-radical grafting method. Polyionic complexes were formed by ionic bonding of the amino groups in EGCG-g-CS with the carboxyl groups in CMC. After lyophilization, a hydrogel with a porous structure was obtained. Scanning electron microscopy (SEM), thermogravimetric differential thermal analysis (TG–DTA), and Fourier transform infrared (FT-IR) analyses of the gel structures were conducted. The swelling properties and porosity of the hydrogels were affected by the grafting ratio. The hydrogel gradually released EGCG under low pH conditions owing to chitosan solubilization, resulting in hydrogel disintegration. Additionally, the hydrogels demonstrated cell adhesion and viability. This study suggests that bio-based materials have potential as pH-dependent catechin-releasing materials. Preparation of hydrogel using catechin-grafted chitosan and carboxymethyl cellulose [ABSTRACT FROM AUTHOR]

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanoparticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ against tumor cells in vivo. In this study, CFZ-loaded tPNPs are stabilized by polycations which have varying pKa values and thus differently modulate nanoparticle stability in response to solution pH. Through polyion complexation, the polycations appeared to stabilize the core of tPNPs entrapping CFZ-cyclodextrin inclusion complexes while allowing for uniform particle size before and after freeze drying. Interestingly, CFZ-loaded tPNPs (CFZ/tPNPs) showed pH-dependent drug release kinetics, which accelerated CFZ release as solution acidity increased (pH < 6) without compromising particle stability at the physiological condition (pH 7.4). In vitro cytotoxicity and proteasome activity assays confirmed that tPNPs stabilized with cationic polymers improved bioactivity of CFZ against CFZ-resistant cancer cells, which would be greatly beneficial in combination with pH-dependent drug release for treatment of solid cancers with drug resistance and tumor microenvironment acidosis by using CFZ and other proteasome inhibitors. [ABSTRACT FROM AUTHOR]

Hydrogels are biomaterials frequently used as carrier systems for wound care, tissue engineering, and local drug applications. Our study aimed to prepare and characterize hydrogels using chitosan and sodium alginate through pH modification. Mechanical properties (hardness, adhesiveness, cohesiveness, compressibility, and elasticity), viscosity, surface morphology, and cytotoxicity of polyion complex hydrogels containing different ratios of sodium alginate and chitosan were investigated. Mechanical properties were determined with a texture analyzer. The viscosity values of hydrogels varied between 12235 and 40743.3 cP. Hydrogel samples absorbed water up to 1000 – 1400% of their weight. The effect of pH and polymer concentration on the structural and mechanical properties of alginate-chitosan hydrogels was demonstrated. The findings showed that the decrease in pH improved the mechanical properties of alginate-chitosan hydrogels and increased the viscosity. The concentrations of chitosan and sodium alginate also altered the properties of hydrogels depending on pH. The formulation H5, which had the highest polymer ratio (3%) and lower pH, showed the highest hardness (0.285 ± 0.018 N), adhesiveness (0.824 ± 0.042 N. s), and compressibility (1.334±0.020 N.mm) values. The results showed that the prepared alginate-chitosan hydrogels are not cytotoxic (cell viability of over 80% in L-929 cell line) and safe for use in living organisms. [ABSTRACT FROM AUTHOR]

[Display omitted] Random insertion of vinylphosphonic acid (VPA) units into a of PEG-PAA block copolymer improves the chemical stability and properties of hybrid nanoobjects obtained from the complexation of the copolymer with metal ions. Block polymers based on poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG) are modified by random insertion of 0 to 100 % of phosphonic acid functions in PAA block by a RAFT polymerization process. These polymers are then used to form hybrid polyionic complexes (HPICs) by complexation with gadolinium or europium ions. The properties of the obtained assemblies are evaluated by magnetic relaxivity, fluorescence and light scattering measurements. The insertion of VPA units within the PAA block increases the chemical stability of the hybrid micelles by maintaining their integrity even at low pH. This insertion also minimizes the exchange of ions between HPICs and the surrounding medium thanks to a strengthening of interactions toward lanthanide ions. When such systems are used as MRI contrast agents or luminescent probe, 50/50 AA/VPA composition appears to be a good compromise to achieve optimal relaxivity or luminescent properties while ensuring a good chemical stability. [ABSTRACT FROM AUTHOR]

Fibers composed of polysaccharides are a promising candidate to be applied for biomaterials such as absorbable surgical sutures, textile fabrics, and hierarchical three-dimensional scaffolds. In this work, in order to fabricate biocompatible fibers with controlled-release abilities, the fabrication of coaxial fibers of calcium alginate (ALG-Ca) and polyion complexes (PICs) consisting of chitosan (CHI) and chondroitin sulfate C (CS), denoted as ALG-PIC fibers, by using a wet spinning process, and the evaluation of their molecular loading and release behavior were performed. The diameter and mechanical strength of the obtained ALG-PIC fibers increased with increasing concentrations of the CHI solution for PIC coatings. This indicated that higher concentrations of the CHI solution afforded a thicker PIC coating layer. Further, fluorescein isothiocyanate labeled-bovine serum albumin (FITC-BSA)-loaded ALG-PIC fibers were successfully prepared. The release behavior of FITC-BSA in the fibers exhibited a slower rate at the initial state than that in ALG-Ca, indicating that PIC coatings suppressed an initial burst release of the loading molecules. Accordingly, the fabricated coaxial fibers can be utilized as sustained-release drug carriers. [ABSTRACT FROM AUTHOR]

Solar-driven water purification has been deemed a promising technology to address the issue of clean water scarcity. However, traditional solar distillers often suffer from low evaporation rates under natural sunlight irradiation, while the high costs of the fabrication of photothermal materials further hinders their practical applications. Here, through the harnessing of the complexation process of oppositely charged polyelectrolyte solutions, a polyion complex hydrogel/coal powder composite (HCC)-based highly efficient solar distiller is reported. In particular, the influence of the charge ratio of polyanion-to-polycation on the solar vapor generation performance of HCC has been systematically investigated. Together with a scanning electron microscope (SEM) and the Raman spectrum method, it is found that a deviation from the charge balance point not only alters the microporous structure of HCC and weakens its water transporting capabilities, but also leads to a decreased content of activated water molecules and enlarges the energy barrier of water evaporation. As a result, HCC prepared at the charge balance point exhibits the highest evaporation rate of 3.12 kg m−2 h−1 under one sun irradiation, with a solar–vapor conversion efficiency as high as 88.83%. HCC also exhibits remarkable solar vapor generation (SVG) performance for the purification of various water bodies. In simulated seawater (3.5 wt% NaCl solutions), the evaporation rate can be as high as 3.22 kg m−2 h−1. In acid and alkaline solutions, HCCs are capable of maintaining high evaporation rates of 2.98 and 2.85 kg m−2 h−1, respectively. It is anticipated that this study may provide insights for the design of low-cost next-generation solar evaporators, and broaden the practical applications of SVG for seawater desalination and industrial wastewater purification. [ABSTRACT FROM AUTHOR]

Polyion complex (PIC) materials have been widely used in biosensors due to their molecular selectivity. However, achieving both widely controllable molecular selectivity and long-term solution stability with traditional PIC materials has been challenging due to the different molecular structures of polycations (poly-C) and polyanions (poly-A). To address this issue, we propose a novel polyurethane (PU)-based PIC material in which the main chains of both poly-A and poly-C are composed of PU structures. In this study, we electrochemically detect dopamine (DA) as the analyte and L-ascorbic acid (AA) and uric acid (UA) as the interferents to evaluate the selective property of our material. The results show that AA and UA are significantly eliminated, while DA can be detected with a high sensitivity and selectivity. Moreover, we successfully tune the sensitivity and selectivity by changing the poly-A and poly-C ratios and adding nonionic polyurethane. These excellent results were employed in the development of a highly selective DA biosensor with a detection range from 500 nM to 100 μM and a 3.4 μM detection limit. Overall, our novel PIC-modified electrode has the potential to advance biosensing technologies for molecular detection. [ABSTRACT FROM AUTHOR]

Mesoscopic-sized polyion complex vesicles (PICsomes) with semi-permeable membranes are promising nanoreactors for enzyme prodrug therapy (EPT), mainly due to their ability to accommodate enzymes in their inner cavity. Increased loading efficacy and retained activity of enzymes in PICsomes are crucial for their practical application. Herein, a novel preparation method for enzyme-loaded PICsomes, the stepwise crosslinking (SWCL) method, was developed to achieve both high feed-to-loading enzyme efficiency and high enzymatic activity under in vivo conditions. Cytosine deaminase (CD), which catalyzes the conversion of the 5-fluorocytosine (5-FC) prodrug to cytotoxic 5-fluorouracil (5-FU), was loaded into PICsomes. The SWCL strategy enabled a substantial increase in CD encapsulation efficiency, up to ~44% of the feeding amount. CD-loaded PICsomes (CD@PICsomes) showed prolonged blood circulation to achieve appreciable tumor accumulation via enhanced permeability and retention effect. The combination of CD@PICsomes and 5-FC produced superior antitumor activity in a subcutaneous model of C26 murine colon adenocarcinoma, even at a lower dose than systemic 5-FU treatment, and showed significantly reduced adverse effects. These results reveal the feasibility of PICsome-based EPT as a novel, highly efficient, and safe cancer treatment modality. [ABSTRACT FROM AUTHOR]

\nImpact StatementsPoly(L-lysine)-block-poly(ethylene glycol)-block-poly(L-lysine) (PLys-block-PEG-block-PLys) triblock copolymers formed polyion complex (PIC) with poly(acrylic acid) (PAAc) or sodium poly(styrenesulfonate) (PSS), leading to the formation of flower micelle-type nanoparticles (NanoLys/PAAc or NanoLys/PSS) with tens of nanometers size in water at a polymer concentration of 10 mg/mL. The flower micelles exhibited irreversible temperature-driven sol-gel transitions at physiological ionic strength, even at low polymer concentrations such as 40 mg/mL, making them promising candidates for injectable hydrogel applications. Rheological studies showed that the chain length of PLys segments and the choice of polyanions significantly impacted irreversible hydrogel formation, with PSS being superior to PAAc for the formation. The incorporation of silica gel nanoparticles into the PIC flower micelles also resulted in irreversible gelation phenomena. The highest storage modulus exceeded 10 kPa after gelation, which is sufficient for practical applications. This study demonstrates the potential of these PIC-based hydrogels as biomaterials with tunable properties for biomedical applications.A polyion complex-based flower micelle, formed by poly(L-lysine)-block-PEG-block- poly(L-lysine) triblock copolymers and polyanions, shows irreversible hydrogel formation; incorporating silica enhanced its modulus to exceeding 10 kPa, promising for biomedical applications. [ABSTRACT FROM AUTHOR]

Functionalized mesoporous silica particles offer excellent chemical and morphological properties, making them ideal adsorbents or drug carriers. However, their synthesis involves several energy- and resource-intensive steps, resulting in high economic and environmental costs. In this study, we report a strategy for the direct design of mesoporous silica with ordered mesopores densely functionalized by polyacid chains. The aqueous process relies on polyion complex micelles acting as pH-responsive multifunctional agents. They are first associated to direct the mesostructure of silica, and are then dissociated by a change in pH to reveal the material's mesoporosity and yield functional pores. Ordered mesoporous particles with controlled structure and particle size were obtained, showing dense functionalization of up to 2.1 mmol.g SiO2 −1 of carboxylic acid functions, which were fully accessible to ionic exchange in aqueous solution. These highly functionalized materials were then evaluated as reversible adsorbents for the removal of a cationic dye (auramine O). The results revealed high dye uptakes, from 130 to 237 mg.g SiO2 −1, which were up to 193 % higher than those achieved with non-functional calcined mesoporous silica particles. These uptakes correlated with the mesoporous volume of the materials, with an average density of around one auramine molecule per nm3 of pore. In addition, the materials exhibited excellent dye adsorption/desorption cyclability by pH stimuli in aqueous solutions under mild conditions, with an average desorption efficiency of 96 % in just 30 min. These results therefore represent an attractive strategy for the design of efficient and sustainable adsorbents for water purification. [Display omitted] • Eco design of ordered mesoporous silica functionalized with poly(acrylic acid) chains. • Direct formation of functionalized mesopores in one pot and two steps. • Highly accessible acid functions are located in hexagonal and cubic mesostructures. • Particle size is controlled by steric stabilization of the surface. • High cationic dye uptake in water, excellent cyclability in response to pH stimuli. [ABSTRACT FROM AUTHOR]

Poly( L -lysine)- block -poly(ethylene glycol)- block -poly( L -lysine) (PLys- block -PEG- block -PLys) triblock copolymers formed polyion complex (PIC) with poly(acrylic acid) (PAAc) or sodium poly(styrenesulfonate) (PSS), leading to the formation of flower micelle-type nanoparticles (Nano Lys/PAAc or Nano Lys/PSS ) with tens of nanometers size in water at a polymer concentration of 10 mg/mL. The flower micelles exhibited irreversible temperature-driven sol-gel transitions at physiological ionic strength, even at low polymer concentrations such as 40 mg/mL, making them promising candidates for injectable hydrogel applications. Rheological studies showed that the chain length of PLys segments and the choice of polyanions significantly impacted irreversible hydrogel formation, with PSS being superior to PAAc for the formation. The incorporation of silica gel nanoparticles into the PIC flower micelles also resulted in irreversible gelation phenomena. The highest storage modulus exceeded 10 kPa after gelation, which is sufficient for practical applications. This study demonstrates the potential of these PIC-based hydrogels as biomaterials with tunable properties for biomedical applications., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

Polyelectrolyte complexes and the derivatives thereof comprise some of the most promising vehicles for the encapsulation and delivery of macromolecular therapeutics. In particular, protein therapeutics, which present a host of special considerations, can often be effectively packaged and delivered using interpolyelectrolyte complexes. While the technologies are still in the developmental phase, there are numerous examples of complexes where control is exerted over spacial and temporal delivery of a model protein cargo or candidate protein therapeutic agent. Here we provide a historical and practical background to promote a deeper understanding of interpolyelectrolyte complexes and the derivative technologies. Additionally, we review the physical principles underlying the association of polyelectrolyte complexes and the application of those principles to novel strategies and technologies driving interpolyelectrolyte complexation. Then, the application of polyelectrolyte complex technology to protein therapeutics is discussed in detail including discussions of several types of protein cargo with a special emphasis on Brain-Derived Neurotrophic Factor. Finally, we focus on the use of stealth polymers in block ionomer complexes, specifically PEG; its benefits, flaws, and possible alternatives. Comprehensive understanding of the field may promote the continued development of derivative technologies for the delivery of particularly intransigent protein therapeutics, much as has been accomplished for small molecule drugs. We also aim to link current advances to the historical developments which inaugurated the field. With consideration to the field, industrial and academic researchers can utilize the discussed technologies and continue to elucidate novel modalities for a myriad of therapeutic and commercial applications. [ABSTRACT FROM AUTHOR]

Fibers composed of polysaccharides are a promising candidate to be applied for biomaterials such as absorbable surgical sutures, textile fabrics, and hierarchical three-dimensional scaffolds. In this work, in order to fabricate biocompatible fibers with controlled-release abilities, the fabrication of coaxial fibers of calcium alginate (ALG-Ca) and polyion complexes (PICs) consisting of chitosan (CHI) and chondroitin sulfate C (CS), denoted as ALG-PIC fibers, by using a wet spinning process, and the evaluation of their molecular loading and release behavior were performed. The diameter and mechanical strength of the obtained ALG-PIC fibers increased with increasing concentrations of the CHI solution for PIC coatings. This indicated that higher concentrations of the CHI solution afforded a thicker PIC coating layer. Further, fluorescein isothiocyanate labeled-bovine serum albumin (FITC-BSA)-loaded ALG-PIC fibers were successfully prepared. The release behavior of FITC-BSA in the fibers exhibited a slower rate at the initial state than that in ALG-Ca, indicating that PIC coatings suppressed an initial burst release of the loading molecules. Accordingly, the fabricated coaxial fibers can be utilized as sustained-release drug carriers.

Polyion complex (PIC) materials have been widely used in biosensors due to their molecular selectivity. However, achieving both widely controllable molecular selectivity and long-term solution stability with traditional PIC materials has been challenging due to the different molecular structures of polycations (poly-C) and polyanions (poly-A). To address this issue, we propose a novel polyurethane (PU)-based PIC material in which the main chains of both poly-A and poly-C are composed of PU structures. In this study, we electrochemically detect dopamine (DA) as the analyte and L-ascorbic acid (AA) and uric acid (UA) as the interferents to evaluate the selective property of our material. The results show that AA and UA are significantly eliminated, while DA can be detected with a high sensitivity and selectivity. Moreover, we successfully tune the sensitivity and selectivity by changing the poly-A and poly-C ratios and adding nonionic polyurethane. These excellent results were employed in the development of a highly selective DA biosensor with a detection range from 500 nM to 100 μM and a 3.4 μM detection limit. Overall, our novel PIC-modified electrode has the potential to advance biosensing technologies for molecular detection.

Many therapeutic formulations incorporate poly(ethylene glycol) (PEG) as a stealth component to minimize early clearance. However, PEG is immunogenic and susceptible to accelerated clearance after multiple administrations. Here, we present two novel reformulations of a polyion complex (PIC), originally composed of poly(ethylene glycol)113-b-poly(glutamic acid)50 (PEG-PLE) and brain-derived neurotrophic factor (BDNF), termed Nano-BDNF (Nano-BDNF PEG-PLE). We replace the PEG based block copolymer with two new polymers, poly(sarcosine)127-b-poly(glutamic acid)50 (PSR-PLE) and poly(methyl-2-oxazolines)38-b-poly(oxazolepropanoic acid)27-b-poly(methyl-2-oxazoline)38 (PMeOx-PPaOx-PMeOx), which are driven to association with BDNF via electrostatic interactions and hydrogen bonding to form a PIC. Formulation using a microfluidic mixer yields small and narrowly disperse nanoparticles which associate following similar principles. Additionally, we demonstrate that encapsulation does not inhibit access by the receptor kinase, which affects BDNF's physiologic benefits. Finally, we investigate the formation of nascent nanoparticles through a series of characterization experiments and isothermal titration experiments which show the effects of pH in the context of particle self-assembly. Our findings indicate that thoughtful reformulation of PEG based, therapeutic PICs with non-PEG alternatives can be accomplished without compromising the self-assembly of the PIC. [ABSTRACT FROM AUTHOR]

A diblock copolymer (P(VBTAC/NaSS)17-b-PAPTAC50; P(VS)17A50) composed of amphoteric random copolymer, poly(vinylbenzyl trimethylammonium chloride-co-sodium p-styrensunfonate) (P(VBTAC/NaSS); P(VS)) and cationic poly(3-(acrylamidopropyl) trimethylammonium chloride) (PAPTAC; A) block, and poly(acrylic acid) (PAAc49) were prepared via a reversible addition−fragmentation chain transfer radical polymerization. Scrips V, S, and A represent VBTAC, NaSS, and PAPTAC blocks, respectively. Water-soluble polyion complex (PIC) vesicles were formed by mixing P(VS)17A50 and PAAc49 in water under basic conditions through electrostatic interactions between the cationic PAPTAC block and PAAc49 with the deprotonated pendant carboxylate anions. The PIC vesicle collapsed under an acidic medium because the pendant carboxylate anions in PAAc49 were protonated to delete the anionic charges. The PIC vesicle comprises an ionic PAPTAC/PAAc membrane coated with amphoteric random copolymer P(VS)17 shells. The PIC vesicle showed upper critical solution temperature (UCST) behavior in aqueous solutions because of the P(VS)17 shells. The pH- and thermo-responsive behavior of the PIC vesicle were studied using 1H NMR, static and dynamic light scattering, and percent transmittance measurements. When the ratio of the oppositely charged polymers in PAPTAC/PAAc was equal, the size and light scattering intensity of the PIC vesicle reached maximum values. The hydrophilic guest molecules can be encapsulated into the PIC vesicle at the base medium and released under acidic conditions. It is expected that the PIC vesicles will be applied as a smart drug delivery system. [ABSTRACT FROM AUTHOR]

The role of neutrophils in tumor metastasis has recently attracted widespread interest. Neutrophils are the most abundant immune cells in human peripheral blood, and large numbers can spontaneously migrate to metastatic sites, where they form an immunosuppressive microenvironment. Polysialic acid (PSA) can target peripheral blood neutrophils (PBNs) mediated by l-selectin, and abemaciclib (ABE) and mitoxantrone (MIT) can treat immunosuppressive microenvironments. Here, we aimed to inhibit lung metastasis of breast cancer and improve chemoimmunotherapy by designing a PSA-modified ABE and MIT co-delivery system (AM-polyion complex (PIC)) to target PBNs in mice with metastatic tumors. We found that through electrostatic interactions between the strong negative charge of PSA and the positive charge of the drug can form stable nanocomplexes and that spontaneous migration of neutrophils can mediate the aggregation of these complexes in the lungs, induce antimetastatic immune responses, enhance the effectiveness of cytotoxic T lymphocytes (CTLs), and inhibit regulatory T cell (Treg) proliferation in vivo and in vitro. Pharmacodynamic results suggested that neutrophil-mediated AM-PIC chemoimmunotherapy inhibited tumor metastasis in mice with lung metastasis of 4T1 breast cancer. Overall, PSA-modified nanocomplexes offer promising neutrophil-mediated, targeted drug delivery systems to treat lung metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

Degradability of polycations under physiological conditions is an attractive feature for their use in biomedical applications, such as the delivery of nucleic acids. This study aims to design polycations with tunable nonenzymatic degradability. A series of cationic N-substituted polyaspartamides were prepared to possess primary amine via various lengths of alkyl spacers in side chains. The degradation rate of each polyaspartamide derivative was determined by size exclusion chromatography under different pH conditions. The N-substituted polyaspartamide containing a 2-aminoethyl moiety in the side chain (PAsp(AE)) showed considerable degradability under physiological conditions (pH 7.4, 37 °C). In contrast, the N-substituted polyaspartamides bearing a longer alkyl spacer in the side chain, i.e. the 3-aminopropyl (PAsp(AP)) and 4-aminobutyl moieties (PAsp(AB)), more strongly suppressed degradation. Further, a positive correlation was observed between the degradation rate of N-substituted polyaspartamides and a deprotonation degree of primary amines in their side chains. Therefore, we conclude that the deprotonated primary amine in the side chain of N-substituted polyaspartamides can induce the degradation of the main chain through the activation of amide nitrogen in the side chain. When N-substituted polyaspartamides were utilized as a messenger RNA (mRNA) delivery vehicle via formation of polyion complexes (PICs), degradable PAsp(AE) elicited significantly higher mRNA expression efficiency in cultured cells compared to PAsp(AP) and PAsp(AB). The higher efficiency of PAsp(AE) might be due to the facilitated destabilization of PICs within the cells, directed toward mRNA release. Additionally, degradation of PAsp(AE) considerably reduced its cytotoxicity. Thus, our study highlights a useful design of well-defined cationic poly(amino acid)s with tunable nonenzymatic degradability.

Many therapeutic formulations incorporate poly(ethylene glycol) (PEG) as a stealth component to minimize early clearance. However, PEG is immunogenic and susceptible to accelerated clearance after multiple administrations. Here, we present two novel reformulations of a polyion complex (PIC), originally composed of poly(ethylene glycol)113-b-poly(glutamic acid)50 (PEG-PLE) and brain-derived neurotrophic factor (BDNF), termed Nano-BDNF (Nano-BDNF PEG-PLE). We replace the PEG based block copolymer with two new polymers, poly(sarcosine)127-b-poly(glutamic acid)50 (PSR-PLE) and poly(methyl-2-oxazolines)38-b-poly(oxazolepropanoic acid)27-b-poly(methyl-2-oxazoline)38 (PMeOx-PPaOx-PMeOx), which are driven to association with BDNF via electrostatic interactions and hydrogen bonding to form a PIC. Formulation using a microfluidic mixer yields small and narrowly disperse nanoparticles which associate following similar principles. Additionally, we demonstrate that encapsulation does not inhibit access by the receptor kinase, which affects BDNF’s physiologic benefits. Finally, we investigate the formation of nascent nanoparticles through a series of characterization experiments and isothermal titration experiments which show the effects of pH in the context of particle self-assembly. Our findings indicate that thoughtful reformulation of PEG based, therapeutic PICs with non-PEG alternatives can be accomplished without compromising the self-assembly of the PIC.

The polyion complexes (PICs) between plasmid DNA (pDNA) and succinylated branched polyethylenimine (bPEI-Et-COOH) were formed for in vivo pDNA delivery by muscular injection. Transmission electron microscopy (TEM) observation revealed that the PIC between pDNA and bPEI-Et-COOH with higher succinylated degree formed the particle structure with corona-like shell. Furthermore, confocal laser scanning microscopy (CLSM) observation revealed that pDNAs were successfully delivered inside the cells and that the pDNAs were colocalized with the nuclei of the cells after endosomal escape. Although the pDNA/bPEI-Et-COOH PICs mediated significant gene expression in vitro, the PICs did not mediate gene expression in vivo muscular injection. Consequently, the pDNA transfection by bPEI-Et-COOH was noncorrelative between in vitro and in vivo in spite of low toxicity by succinylation both in vitro and in vivo. The noncorrelative relation between in vitro and in vivo for pDNA transfection by bPEI-Et-COOH muscular injection would be considerable design for pDNA carriers in vivo. [ABSTRACT FROM AUTHOR]

[Display omitted] • Carboxylated trithiocarbonate mediates RAFT polymerization of a bisphosphonic acrylate. • Two RAFT methodologies lead to phosphonated double hydrophilic block copolymers. • DHBCs interact with lanthanide ions (Gd, Eu) to form polyionic complexes. • Bisphosphonated polyionic complexes enhance the stability of MRI contrast agents. The synthesis of double hydrophilic block copolymers (DHBCs) with one block containing bisphosphonic acid groups was performed by aqueous RAFT polymerization with two approaches, either starting from a PEO-based macro-chain transfer agent (macro-CTA) or by chain extension of a RAFT-capped bisphosphonic acrylate homopolymer with oligo(ethylene glycol) methyl ether acrylate (OEGA). By complexation with gadolinium and europium ions, these polymers are prone to form hybrid polyionic complexes (HPICs) as evidenced by mono- and multi-angle DLS, TEM and luminescence measurements. The obtained HPICs showed better chemical stability at low pH values compared to previously reported counterparts based on carboxylic and monophosphonic acid groups (i.e., PEO- b -PAA and PEO- b -PVPA respectively). Due to their high relaxivity values, the proposed HPICs show potential as contrast agents for magnetic resonance imaging (MRI). [ABSTRACT FROM AUTHOR]

Abstract Background Polymeric micelles attract great attention in drug delivery and therapeutics. Various types of block copolymers have been designed for the application in biomedical fields. If we can introduce additional functional groups to the block copolymers, we can achieve advanced applications. In this regards, we tried to introduce aggregation induced emission enhancement (AIE) unit in the block copolymer. Methods The formation of polyion complex micelle was confirmed by dynamic light scattering and transmission electron microscopy. HeLa cells were incubated with polyion complex micelle and broad-band visible light using a halogen lamp (150 W) was irradiated to evaluate photocytotoxicity of polyion complex (PIC) micelle. Results For the design of functional polymeric micelle, aggregation induced emission enhancement unit was introduced in the middle of block copolymer. We newly synthesized a new type block copolymer (PEG-TPE-PEI) possessing tetraphenylethene (TPE) group, as an AIE unit, in the middle of polymeric segments of PEG and PEI, which successfully formed PIC micelle with DP. The formation of PIC micelle was confirmed by dynamic light scattering, ζ potential measurement and transmission electron microscopy. Conclusions PEG-TPE-PEI successfully formed PIC micelle by mixing with negatively charged dendrimer porphyrin. The PIC micelle exhibited photocytotoxicity upon illumination of broadband visible light.

Degradability of polycations under physiological conditions is an attractive feature for their use in biomedical applications, such as the delivery of nucleic acids. This study aims to design polycations with tunable nonenzymatic degradability. A series of cationic N-substituted polyaspartamides were prepared to possess primary amine via various lengths of alkyl spacers in side chains. The degradation rate of each polyaspartamide derivative was determined by size exclusion chromatography under different pH conditions. The N-substituted polyaspartamide containing a 2-aminoethyl moiety in the side chain (PAsp(AE)) showed considerable degradability under physiological conditions (pH 7.4, 37 °C). In contrast, the N-substituted polyaspartamides bearing a longer alkyl spacer in the side chain, i.e. the 3-aminopropyl (PAsp(AP)) and 4-aminobutyl moieties (PAsp(AB)), more strongly suppressed degradation. Further, a positive correlation was observed between the degradation rate of N-substituted polyaspartamides and a deprotonation degree of primary amines in their side chains. Therefore, we conclude that the deprotonated primary amine in the side chain of N-substituted polyaspartamides can induce the degradation of the main chain through the activation of amide nitrogen in the side chain. When N-substituted polyaspartamides were utilized as a messenger RNA (mRNA) delivery vehicle via formation of polyion complexes (PICs), degradable PAsp(AE) elicited significantly higher mRNA expression efficiency in cultured cells compared to PAsp(AP) and PAsp(AB). The higher efficiency of PAsp(AE) might be due to the facilitated destabilization of PICs within the cells, directed toward mRNA release. Additionally, degradation of PAsp(AE) considerably reduced its cytotoxicity. Thus, our study highlights a useful design of well-defined cationic poly(amino acid)s with tunable nonenzymatic degradability. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Heparin is a versatile building block to construct biomedical polyion complex(PIC). • PIC's morphologies are tuned from micelle to vesicle by heparin content. • The PIC drug carrier with high DLC is prepared by very simple manipulation. • pH sensitive release is spontaneously endowed without additional modification. • Heparin PIC drug carrier has significant cytotoxicity against tumor cell in vitro. Abstract Heparin as negative polysaccharide is a universal building block to form polyion complex with different cationic counterparts. In this paper, three different cations, including chitosan, benzyldodecyldimethyl ammonium bromide and doxorubicin hydrochloride, were used to prepare heparin-based polyion complexes (HPICs). Their morphologies could be tuned by heparin content in HPIC, and they also showed pH-sensitive decomposition. Doxorubicin was further encapsulated into micelle and vesicle carrier made from heparin-benzyldodecyl dimethyl ammonium bromide PIC, whereas heparin-doxorubicin PIC could be directly used as drug carrier. In vitro drug release proved the drug carriers exhibit obvious pH sensitive release behaviour. Cytotoxicity indicated the drug carrier possessed significant cytotoxicity to tumor cells. The cell uptake observed by CLSM showed the carrier was able to deliver antitumor drug into tumor cell's nucleus. Consequently, these results showed the promising potential of HPIC in drug carrier application. [ABSTRACT FROM AUTHOR]

Abstract Cancer stem-like cells (CSCs) treatment is a plausible strategy for enhanced cancer therapy. Here we report a glucose-installed sub-50-nm nanocarrier for the targeted delivery of small interfering RNA (siRNA) to CSCs through selective recognition of the glucose ligand to the glucose transporter 1 (GLUT1) overexpressed on the CSC surface. The siRNA nanocarrier was constructed via a two-step assembling process. First, a glucose-installed poly(ethylene glycol)- block -poly(l -lysine) modified with lipoic acid (LA) at the ω-end (Glu-PEG-PLL-LA) was associated with a single siRNA to form a unimer polyion complex (uPIC). Second, a 20 nm gold nanoparticle (AuNP) was decorated with ~65 uPICs through Au S bonding. The glucose-installed targeted nanoparticles (Glu-NPs) exhibited higher cellular uptake of siRNA payloads in a spheroid breast cancer (MBA-MB-231) cell culture compared with glucose-unconjugated control nanoparticles (MeO-NPs). Notably, the Glu-NPs became more efficiently internalized into the CSC fraction, which was defined by aldehyde dehydrogenase (ALDH) activity assay, than the other fractions, probably due to the higher GLUT1 expression level on the CSCs. The Glu-NPs elicited significantly enhanced gene silencing in a CSC-rich orthotopic MDA-MB-231 tumor tissue following systemic administration to tumor-bearing mice. Ultimately, the repeated administrations of polo-like kinase 1 (PLK1) siRNA-loaded Glu-NPs significantly suppressed the growth of orthotopic MDA-MB-231 tumors. These results demonstrate that Glu-NP is a promising nanocarrier design for CSC-targeted cancer treatment. Graphical abstract Unlabelled Image Highlights • Glucose-installed nanoparticle (Glu-NP) was made for cancer stem cell-targeted siRNA delivery. • Glu-NP was made by conjugating unimer polyion complexes on Au nanoparticle. • Enhanced cellular uptake of Glu-NP was observed in cancer stem cells in spheroid culture. • Glu-NP loaded with PLK1 siRNA suppressed growth of orthotopic breast tumor model. [ABSTRACT FROM AUTHOR]

In this work, a tight polyethersulfone (PES) -based ultrafiltration (UF) membrane was fabricated to separate dye and salt of textile wastewater via a novel polyion complex assisted phase inversion method in one step. Thereinto, sulfonated polysulfone (SPSF) and poly-(diallyl dimethylammonium chloride) (PDADMAC) were added into the PES dope and coagulation bath, respectively. During the phase inversion process of the precast PES/SPSF film, polycation PDADMAC could assemble with anionic SPSF and facilitate SPSF enrichment on membrane surface, forming a dense barrier layer via the electrostatic interaction between quaternary ammonium and sulfonate groups. Morphology, chemical composition, surface charges and pore size analysis characterized via SEM, FTIR, XPS, Zeta potential and Dextran filtration experiment, respectively, testified that a nonporous skin layer comprising of polyion complex and enriched SPSF was successfully constructed on the top of the PES matrix with an effective pore radius of 1.44 nm, which is smaller than that of the reference membrane prepared without using polyion complex assisted phase inversion (2.74 nm). This resultant membrane exhibited a high pure water permeance of 94 LMH/bar. When it was utilized to separate a dye/salt mixture of 100 ppm Congo red (CR) and 2 g/L Na 2 SO 4 at 1 bar, the rejection of CR could reach 99.7%, alongside a very low Na 2 SO 4 rejection of 8.4%, while the water permeance of dye solution maintained 61 LMH/bar. In addition, the membrane also possessed excellent stability in the pH range of 1–13 due to the strong electrostatic interaction between SPSF and PDADMAC and long-term operation stability, demonstrating its application potential in textile wastewater treatment. [Display omitted] • Tight UF membranes were prepared via polyion complex assisted phase inversion. • The assembly between SPSF and PDADMAC made a thin and nonporous skin layer. • The membrane exhibited 99.7% and 8.4% of Congo red and Na 2 SO 4 rejections, respectively, alongside 61 LMH/bar water permeance. • The separation performance can maintain in the pH range of 1–13 and 12-h stability testing. [ABSTRACT FROM AUTHOR]

For high-valued application of natural DNA as raw materials, we prepared nanocarriers by using salmon sperm DNA and chitosan to encapsulate water-insoluble bioactives. Here, water dispersible astaxanthin/DNA/chitosan nano-aggregates (ADC-NAs) were prepared by co-assemble evaporation method. The key point for preparing well formed ADC-NAs was specifically discussed. The resultant ADC-NAs were spherical with 100–300 nm diameter measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and their homogeneous dispersions were sufficiently stable at room temperature. One important feature of these nanocarriers is enormously high loading amount of cargo (about 40 wt%). According to the UV–Vis spectra of the nanosuspension, we deduced that astaxanthin was encapsulated as uniquely structured J-aggregates. Fourier transform infra-red (FTIR) spectroscopy proved fabrication was successfully and astaxanthin was embedding in DNA/chitosan nanocarriers. Cytotoxicity was examined in vitro using cell culture in L929 cell lines. When necessary, these nano-aggregates can be degraded by DNase I. Homogeneous dispersions of other non-charged guest molecules are also prepared by using DNA/chitosan nanocarriers. These dispersions are cheaply and easily obtainable from naturally occurring DNA and chitosan, and should be useful for versatile applications. [ABSTRACT FROM AUTHOR]

Herein, we report the fabrication of a polyion complex hydrogel from two oppositely charged derivatives of cellulose nanofibrils (CNF). CNF was produced from dissolving pulp through subsequent periodate oxidation, chemical modification, and microfluidization. Three different durations for periodate oxidation (30 min, 120 min, and 180 min) resulted in three different aldehyde contents. Further, two types of chemical modifications were introduced to react with the resulting aldehydes: chlorite oxidation to yield anionic CNF with carboxylic acid groups (DCC) and imination with Girard’s reagent T to yield cationic CNF containing quaternary ammonium groups (CDAC). Functional group contents were assessed using conductometric titration and elemental analysis, while nanofibril morphologies were assessed using atomic force microscopy (AFM). Longer durations of periodate oxidation did not yield different width profile but was found to decrease fibril length. The formation of self-standing hydrogel through mixing of DCC and CDAC dispersions was investigated. Oscillatory rheology was performed to assess the relative strengths of different gels. Self-standing hydrogels were obtained from mixture of DCC180 and CDAC180 dispersions in acetate buffer at pH 4 and 5 at a low concentration of 0.5% w/w that displayed approximately 10-fold increase in storage and loss moduli compared to those of the individual dispersions. Self-standing gels containing doxorubicin (an anticancer drug) displayed pH-responsive release profiles. At physiological pH 7.4, approximately 65% of doxorubicin was retained past a burst release regime, while complete release was observed within 5 days at pH 4. Biocompatibility of DCC180, CDAC180, and their mixture were investigated through quantification of the metabolic activity of NIH3T3 cells in vitro . No significant cytotoxicity was observed at concentrations up to 900 µg/mL. In short, the nanocellulose-based polyion complex hydrogels obtained in this study are promising nature-derived materials for biomedical applications. Statement of Significance We demonstrate that polyion complex can be formed between two cellulose nanofibrils containing complementary charges. To the best of our knowledge, this is the first time that polyion complex formation between complementarily-modified cellulose nanofibrils has been reported, and the results may lead to new ideas on applications of the very promising nanocellulosic materials. The polyion complex helps form a self-standing network that is demonstrated to provide controlled and pH-responsive release of doxorubicin. Particularly, the report explores the connection between the physical properties of functionalizable nanocellulosic materials and their potential biomedical applications. Thus, the study encompasses several broad fields of materials science and engineering, chemistry, and biomedical science that we believe is in line with the readers’ interests. [ABSTRACT FROM AUTHOR]

Copyright of Kobunshi Ronbunshu is the property of Society of Polymer Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Kobunshi Ronbunshu is the property of Society of Polymer Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An amphoteric random copolymer (P(SA)91) composed of anionic sodium 2-acrylamido-2-methylpropanesulfonate (AMPS, S) and cationic 3-acrylamidopropyl trimethylammonium chloride (APTAC, A) was prepared via reversible addition-fragmentation chain transfer (RAFT) radical polymerization. The subscripts in the abbreviations indicate the degree of polymerization (DP). Furthermore, AMPS and APTAC were polymerized using a P(SA)91 macro-chain transfer agent to prepare an anionic diblock copolymer (P(SA)91S67) and a cationic diblock copolymer (P(SA)91A88), respectively. The DP was estimated from quantitative 13C NMR measurements. A stoichiometrically charge neutralized mixture of the aqueous P(SA)91S67 and P(SA)91A88 formed water-soluble polyion complex (PIC) micelles comprising PIC cores and amphoteric random copolymer shells. The PIC micelles were in a dynamic equilibrium state between PIC micelles and charge neutralized small aggregates composed of a P(SA)91S67/P(SA)91A88 pair. Interactions between PIC micelles and fetal bovine serum (FBS) in phosphate buffered saline (PBS) were evaluated by changing the hydrodynamic radius (Rh) and light scattering intensity (LSI). Increases in Rh and LSI were not observed for the mixture of PIC micelles and FBS in PBS for one day. This observation suggests that there is no interaction between PIC micelles and proteins, because the PIC micelle surfaces were covered with amphoteric random copolymer shells. However, with increasing time, the diblock copolymer chains that were dissociated from PIC micelles interacted with proteins. [ABSTRACT FROM AUTHOR]

The high affinity of positively charged nanoparticles to biological interfaces makes them easily taken up by tumor cells but limits their tumor permeation due to non-specific electrostatic interactions. In this study, polyion complex coated nanoparticles with different charge reversal profiles were developed to study the influence of charge reversal profile on tumor penetration. The system was constructed by polyion complex coating using micelles composed of poly (lysine)- b -polycaprolactone (PLys- b -PCL) as the cationic core and poly (glutamic acid)- g - methoxyl poly (ethylene glycol) (PGlu- g -mPEG) as the anionic coating material. Manipulation of charge reversal profile was achieved by controlling the polymer chain entanglement and electrostatic interaction in the polyion complex layer through glutaraldehyde-induced shell-crosslinking. The delayed charge reversal nanoparticles (CTCL30) could maintain negatively charged in pH 6.5 PBS for at least 2 h and exhibit pH-responsive cytotoxicity and cellular uptake in an extended time scale. Compared with a faster charge reversal counterpart (CTCL70) with similar pharmacokinetic profile, CTCL30 showed deeper penetration, higher in vivo tumor cell uptake and stronger antitumor activity in vivo (tumor inhibition rate: 72.3% vs 60.2%, compared with CTCL70). These results indicate that the delayed charge reversal strategy could improve therapeutic effect via facilitating tumor penetration. Statement of Significance Here, the high tumor penetration capability of PEG-coated nanoparticles and the high cellular uptake of cationic nanoparticles were combined by a delayed charge reversal drug delivery system. This drug delivery system was composed of a drug-loading cationic inner core and a polyion complex coating. Manipulation of charge reversal profile was realized by varying the crosslinking degree of the shell of the cationic inner core, through which changed the strength of the polyion complex layer. Nanoparticles with delayed charge reversal profile exhibited improved tumor penetration, in vivo tumor cell uptake and in vivo tumor growth inhibition effect although they have similar pharmacokinetic and biodistribution behaviors with their instant charge reversal counterpart. [ABSTRACT FROM AUTHOR]

A bioanode for ethanol oxidation was prepared by immobilizing the recombinant pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenase from Pseudomonas putida KT 2440 (PpADH) with polyion complex (PIC) and redox polymer. The PIC based on poly-L-lysine (PLL) and poly-L-glutamic acid (PGA) was suitable for immobilizing PpADH on the electrode. PpADH was immobilized using only one redox polymer, aminoferrocene, which was attached to the PGA backbone (PGA-AmFc) on the electrode. The anodic current density at 0.6 V (vs. Ag/AgCl) was 22.6 µA·cm-2However, when the number of the cycles was increased, the catalytic current drastically decreased. PpADH was immobilized using PGA-AmFc and PIC on the electrode. The anodic current density at 0.5 V (vs. Ag/AgCl) was 47.3 µA·cm-2 and the performance maintained 74% of the initial value after five cycles. This result indicated that the combination of PIC and PGA-AmFc was suitable for the immobilization of PpADH on the electrode. In addition, the long-term stability and catalytic current density were improved by using the large surface area afforded by the gold nanoparticles. [ABSTRACT FROM AUTHOR]

Surface functionalization of nanoparticles is a crucial factor for nanoparticle-mediated drug and nucleic acid delivery. Particularly, the density of targeting ligands on nanoparticle significantly affects the affinity of nanoparticles to specific cellular surface (or receptor) through the multivalent binding effect. Herein, multilayered polyion complexes (mPICs) are prepared to possess varying densities of cyclic RGD peptide (cRGD) ligands for cancer-targeted small interfering RNA (siRNA) delivery. A template PIC is first prepared by mixing siRNAs with homo catiomers of N-substituted polyaspartamide bearing tetraethylenepentamine (PAsp(TEP)) in aqueous solution, followed by silica-coating through silicate condensation reaction. Then, silica-coated PICs (sPICs) are further covered with block catiomers of PAsp(TEP) and poly(ethylene glycol) (PEG) equipped with cRGD ligand. Successful preparation of targeted mPICs is confirmed from the changes in size and ζ-potential and the elemental analysis by transmission electron microscopy. Notably, the number of cRGD ligands per mPIC is regulated by altering the silicate concentration upon preparation of sPICs, which is confirmed by fluorescence correlation spectroscopy using fluorescent-labeled block catiomers. Ultimately, the targeted mPICs with a higher number of cRGD ligands demonstrate more efficient cellular uptake in cultured cancer cells, leading to enhanced gene silencing activity. [ABSTRACT FROM AUTHOR]

We have developed inducible cell self-organization through weakly positively charged culture surfaces. In this study, a thermoresponsive and zwitterionic copolymer comprised of N,N-dimethylaminoethyl methacrylate (DMAEMA) and methacrylic acid (MA) (PDMAEMA- co-PMA; Mn: ∼9.7 × 104 g/mol; PDMAEMA/PMA ratio: 10) was designed for inducing cell self-organization. The copolymer formed single polymer-derived polyion complex (sPIC) nanoparticles following dissolution in an aqueous solution. The sPIC nanoparticles had a positive charge (ca. 25 mV). Self-organization occurred in adipose-derived vascular stromal cell monolayers cultivated on sPIC-deposited surfaces. There were dramatic morphological changes of these cells with the formation of capillary-like networks and single-cell aggregates with little cytotoxicity. This was a significant improvement compared with cells grown on previously developed surfaces deposited with PIC, a mixture of PDMAEMA and plasmid DNA. Thus, sPICs of PDMAEMA- co-PMA may allow for the accurate evaluation of a variety of cell behaviors with less cytotoxicity, and may facilitate additional potential medical applications such as cell-based therapy and drug discovery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1009-1015, 2017. [ABSTRACT FROM AUTHOR]

Diblock copolymers consisting of a hydrophilic poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) block and either a cationic or anionic block were prepared from (3-(methacrylamido)propyl)trimethylammonium chloride (MAPTAC) or sodium 2-(acrylamido)-2- methylpropanesulfonate (AMPS). Polymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) radical polymerization using a PMPC macro-chain transfer agent. The degree of polymerization for PMPC, cationic PMAPTAC, and anionic PAMPS blocks was 20, 190, and 196, respectively. Combining two solutions of oppositely charged diblock copolymers, PMPC-b-PMAPTAC and PMPC-b-PAMPS, led to the spontaneous formation of polyion complex vesicles (PICsomes). The PICsomes were characterized using 1H NMR, static abd dynamic light scattering, transmittance electron microscopy (TEM), and atomic force microscopy. Maximum hydrodynamic radius (Rh) for the PICsome was observed at a neutral charge balance of the cationic and anionic diblock copolymers. The Rh value and aggregation number (Nagg) of PICsomes in 0.1 M NaCl was 78.0 nm and 7770, respectively. A spherical hollow vesicle structure was observed in TEM images. The hydrodynamic size of the PICsomes increased with concentration of the diblock copolymer solutions before mixing. Thus, the size of the PICsomes can be controlled by selecting an appropriate preparation method. [ABSTRACT FROM AUTHOR]

Poly(L-lysine)-block-poly(ethylene glycol)-block-poly(L-lysine) (PLys-block-PEG-block-PLys) triblock copolymers formed polyion complex (PIC) with poly(acrylic acid) (PAAc) or sodium poly(styrenesulfonate) (PSS), leading to the formation of flower micelle-type nanoparticles (NanoLys/PAAc or NanoLys/PSS) with tens of nanometers size in water at a polymer concentration of 10 mg/mL. The flower micelles exhibited irreversible temperature-driven sol-gel transitions at physiological ionic strength, even at low polymer concentrations such as 40 mg/mL, making them promising candidates for injectable hydrogel applications. Rheological studies showed that the chain length of PLys segments and the choice of polyanions significantly impacted irreversible hydrogel formation, with PSS being superior to PAAc for the formation. The incorporation of silica gel nanoparticles into the PIC flower micelles also resulted in irreversible gelation phenomena. The highest storage modulus exceeded 10 kPa after gelation, which is sufficient for practical applications. This study demonstrates the potential of these PIC-based hydrogels as biomaterials with tunable properties for biomedical applications.