pH- and Photoresponsive Liquid Plasticine.

Liquid marbles (LMs) can be prepared by adsorption of hydrophobic particles at the air-liquid interface of a water droplet. LMs have been studied for their application as microreaction vessels. However, their opaqueness poses challenges for internal observation. Liquid plasticines (LPs), akin to LMs, can be prepared by the adsorption of hydrophobic particles with a diameter of 50 nm or less, at the air-liquid interface of a water droplet. Unlike LMs, LPs are transparent, allowing for internal observation, thus presenting promising applications as reactors and culture vessels on a microliter scale. In this study, the surface of silica particles, approximately 20 nm in diameter, was rendered hydrophobic to prepare hydrophobic silica particles (SD0). A small amount of poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) was then grafted onto the surface of SD0, yielding SD1. SD0 particles exhibited consistent hydrophobicity irrespective of the environmental pH atmosphere. Under acidic conditions, SD1 became hydrophilic due to the protonation of pendant tertiary amines in the grafted PDPA chains. However, SD1 alone was unsuitable for LP preparation due to its high surface wettability regardless of atmospheric pH, attributable to the presence of PDPA-grafted chains. Therefore, to prepare pH-responsive LP, SD1 and SD0 were mixed (SD1/SD0 = 3/7). Upon exposure to HCl gas, these LPs ruptured, with the leaked water from the LPs being absorbed by adjacent paper. Moreover, clear LPs, prepared using an aqueous solution containing a water-soluble photoacid generator (PAG), disintegrated upon exposure to light as PAG generated acid, leading to LP breakdown. In summary, pH-responsive LPs, capable of disintegration under acidic conditions and upon light irradiation, were successfully prepared in this study.

The Effect of Block Ratio and Structure on the Thermosensitivity of Double and Triple Betaine Block Copolymers.

AB-type and BAB-type betaine block copolymers composed of a carboxybetaine methacrylate and a sulfobetaine methacrylate, PGLBT-b-PSPE and PSPE-b-PGLBT-b-PSPE, respectively, were synthesized by one-pot RAFT polymerization. By optimizing the concentration of the monomer, initiator, and chain transfer agent, block extension with precise ratio control was enabled and a full conversion (~99%) of betaine monomers was achieved at each step. Two sets (total degree of polymerization: ~300 and ~600) of diblock copolymers having four different PGLBT:PSPE ratios were prepared to compare the influence of block ratio and molecular weight on the temperature-responsive behavior in aqueous solution. A turbidimetry and dynamic light scattering study revealed a shift to higher temperatures of the cloud point and micelle formation by increasing the ratio of PSPE, which exhibit upper critical solution temperature (UCST) behavior. PSPE-dominant diblocks created spherical micelles stabilized by PGLBT motifs, and the transition behavior diminished by decreasing the PSPE ratio. No particular change was found in the diblocks that had an identical AB ratio. This trend reappeared in the other set whose entire molecular weight approximately doubled, and each transition point was not recognizably impacted by the total molecular weight. For triblocks, the PSPE double ends provided a higher probability of interchain attractions and resulted in a more turbid solution at higher temperatures, compared to the diblocks which had similar block ratios and molecular weights. The intermediates assumed as network-like soft aggregates eventually rearranged to monodisperse flowerlike micelles. It is expected that the method for obtaining well-defined betaine block copolymers, as well as the relationship of the block ratio and the chain conformation to the temperature-responsive behavior, will be helpful for designing betaine-based polymeric applications.

Formation of Polyion Complex Aggregate Formed from a Cationic Block Copolymer and Anionic Polysaccharide.

Block copolymers (PmMn; P20M101 and P100M98) comprising poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC, P) containing biocompatible phosphorylcholin pendants and cationic poly((3-acryloylaminopropyl) trimethylammonium chloride) (PMAPTAC, M) were synthesized via a controlled radical polymerization method. The degrees of polymerization of the PMPC and PMAPTAC segments are denoted by subscripts (PmMn). The mixture of cationic PmMn and anionic sodium chondroitin sulfate C (CS) with the pendant anionic carboxylate and sulfonate groups formed polyion complex (PIC) aggregates in phosphate-buffered saline. A charge-neutralized mixture of P20M101 with CS formed P20M101/CS PIC vesicles with a hydrodynamic radius (Rh) of 97.2 nm, zeta potential of ca. 0 mV, and aggregation number (Nagg) of 23,044. PMPC shells covered the surface of the PIC vesicles. The mixture of P100M98 and CS formed PIC spherical micelles with the PIC core and hydrophilic PMPC shells. The Rh, zeta potential, and Nagg of the PIC micelles were 26.4 nm, ca. 0 mV, and 404, respectively. At pH < 4, the carboxylate anions in CS were protonated. Thus, the charge balance in the PIC micelles shifted to decrease the core density owing to the electrostatic repulsions of the excess cations in the core. The PIC micelles dissociated at a NaCl concentration ≥0.6 M owing to the charge screening effect. The positively charged PIC micelles with excess P100M98 can encapsulate anionic dyes owing to electrostatic interaction.

Removal of Acid Orange G Azo Dye by Polycation-Modified Alpha Alumina Nanoparticles.

Highly positively charged poly(vinyl benzyl trimethylammonium chloride) (PVBMA) was successfully synthesized with approximately 82% of yield. The PVBMA was characterized by the molecular weight (Mw ) of 343.45 g mol-1 and the molecular weight distribution, (D) of 2.4 by 1 H NMR and SEC measurements. The PVBMA was applied as an effective agent for α-Al2 O3 surface modification in the adsorptive removal of the azo dye acid orange G (AOG). The AOG removal performance was significantly enhanced at all pH compared to without surface modification. The experimental parameters were optimal at pH 8, free ionic strength, 15 min of adsorption time, and 5 mg mL-1 α-Al2 O3 adsorbents. The AOG adsorption which was mainly controlled by the PVBMA-AOG electrostatic attractions was better applicable to the Langmuir isotherm and the pseudo-second kinetic model. The PVBMA-modified α-Al2 O3 demonstrates a high-performance and highly reusable adsorbent with great AOG performances of approximately 90.1% after 6 reused cycles.

Special Issue "State-of-the-Art Polymer Science and Technology in Japan (2021, 2022)".

It has been 100 years since the first article on polymerization was published by Hermann Staudinger [...].

Comparison between Cashew-Based and Petrochemical Hydroxyoximes: Insights from Molecular Simulations.

Solvent extraction has been ubiquitously used to recover valuable metals from wastes such as spent batteries and electrical boards. With increasing demands for energy transition, there is a critical need to improve the recycling rate of critical metals, including copper. Therefore, the sustainability of reagents is critical for the overall sustainability of the process. Yet, the recycling process relies on functional organic compounds based on the hydroxyoxime group. To date, hydroxyoxime extractants have been produced from petrol-based chemical feedstocks. Recently, natural-based cardanol has been used to produce an alternative hydroxyoxime. The natural-based oxime has been employed to recover valuable metals (Ga, Ni, Co) via a liquid/liquid extraction process. The natural compound has a distinctive structure with 15 carbons in the alkyl tail. In contrast, petrol-based hydroxyoximes have only 12 or fewer carbons. However, the molecular advantages of this natural-based compound over the current petrol-based ones remain unclear. In this study, molecular dynamics simulation was employed to investigate the effect of extractant hydrocarbon chains on the extraction of copper ions. Two hydroxyoxime extractants with 12 and 15 carbons in the alkyl chain were found to have similar interactions with Cu2+ ions. Yet, a slight molecular binding increase was observed when the carbon chain was increased. In addition, lengthening the carbon chain made the extracting stage easier and the stripping stage harder. The binding would result in a lower pH in the extraction step and a lower pH in the stripping step. The insights from this molecular study would help design the extraction circuit using natural-based hydroxyoxime extractants. A successful application of cashew-based cardanol will improve the environmental benefits of the recycling process. With cashew-producing regions in developing countries, the application also improves these regions' social and economic sustainability.

Preparation of Water-Soluble Polyion Complex (PIC) Micelles with Random Copolymers Containing Pendant Quaternary Ammonium and Sulfonate Groups.

Cationic random copolymers (PCm) consisting of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC; P) with methacroylcholine chloride (MCC; C) and anionic random copolymers (PSn) consisting of MPC and potassium 3-(methacryloyloxy)propanesulfonate (MPS; S) were prepared via a reversible addition-fragmentation chain transfer method. "m" and "n" represent the compositions (mol %) of the MCC and MPS units in the copolymers, respectively. The degrees of polymerization for the copolymers were 93-99. Water-soluble MPC unit contains a pendant zwitterionic phosphorylcholine group whose charges are neutralized in pendant groups. MCC and MPS units contain the cationic quaternary ammonium and anionic sulfonate groups, respectively. The stoichiometrically charge-neutralized mixture of a matched pair of PCm and PSn aqueous solutions resulted in the spontaneous formation of water-soluble PCm/PSn polyion complex (PIC) micelles. These PIC micelles have the MPC-rich surface and MCC/MPS core. These PIC micelles were characterized using 1H NMR, dynamic and static light scattering, and transmission electron microscopic measurements. The hydrodynamic radius of these PIC micelles depends on the mixing ratio of the oppositely charged random copolymers. The charge-neutralized mixture formed maximum-size PIC micelles.

Single-Micelle-Templated Synthesis of Hollow Barium Carbonate Nanoparticle for Drug Delivery.

A laboratory-synthesized triblock copolymer poly(ethylene oxide-b-acrylic acid-b-styrene) (PEG-PAA-PS) was used as a template to synthesize hollow BaCO3 nanoparticles (BC-NPs). The triblock copolymer was synthesized using reversible addition-fragmentation chain transfer radical polymerization. The triblock copolymer has a molecular weight of 1.88 × 104 g/mol. Transmission electron microscopy measurements confirm the formation of spherical micelles with a PEG corona, PAA shell, and PS core in an aqueous solution. Furthermore, the dynamic light scattering experiment revealed the electrostatic interaction of Ba2+ ions with an anionic poly(acrylic acid) block of the micelles. The controlled precipitation of BaCO3 around spherical polymeric micelles followed by calcination allows for the synthesis of hollow BC-NPs with cavity diameters of 15 nm and a shell thickness of 5 nm. The encapsulation and release of methotrexate from hollow BC-NPs at pH 7.4 was studied. The cell viability experiments indicate the possibility of BC-NPs maintaining biocompatibility for a prolonged time.

A New Year's Message 2023.

We wish you all happiness, health and progress in the new year [...].

A Thermo-Responsive Polymer Micelle with a Liquid Crystalline Core.

An amphiphilic diblock copolymer (PChM-PNIPAM), composed of poly(cholesteryl 6-methacryloyloxy hexanoate) (PChM) and poly(N-isopropyl acrylamide) (PNIPAM) blocks, was prepared via reversible addition-fragmentation chain transfer radical polymerization. The PChM and PNIPAM blocks exhibited liquid crystalline behavior and a lower critical solution temperature (LCST), respectively. PChM-PNIPAM formed water-soluble polymer micelles in water below the LCST because of hydrophobic interactions of the PChM blocks. The PChM and PNIPAM blocks formed the core and hydrophilic shell of the micelles, respectively. With increasing temperature, the molecular motion of the pendant cholesteryl groups increased, and a liquid crystalline phase transition occurred from an amorphous state in the core. With further increases in temperature, the PNIPAM block in the shell exhibited the LCST and dehydrated. Hydrophobic interactions of the PNIPAM shells resulted in inter-micellar aggregation above the LCST.

Mechanistic insights and importance of hydrophobicity in cationic polymers for cancer therapy.

Development of molecules that can be effectively used for killing cancer cells remains a research topic of interest in drug discovery. However, various limitations of small molecules and nanotechnology-based drug-delivery systems hinder the development of chemotherapeutics. To resolve this issue, this study describes the potential application of polymeric molecules as anticancer drug candidates. We describe the design and synthesis of novel anticancer polymers containing hydrophobic groups. We established the fact that the cationic homopolymer (PAMPTMA) does not show any anticancer activity on its own; however, the insertion of hydrophobic moieties in copolymers (PAMPTMA-r-BuMA, PAMPTMA-r-HexMA, and PAMPTMA-r-OctMA) enhances their anticancer activity with a very low IC50 value (60 µg mL-1 for HepG2 cells). Mechanistic investigations were carried out using LDH leakage assay, cellular uptake, DOSY NMR and molecular dynamics to study the interaction between the polymer and the cell membrane as well as the role of hydrophobicity in enhancing this interaction. The results demonstrated that polymers are attracted by the anionic cancer cell membrane, which then leads to the insertion of hydrophobic groups inside the cell membrane, causing its disruption and ultimate lysis of the cell. This study demonstrates a novel and better approach for the rational design and discovery of new polymeric anticancer agents with improved efficacy.

Recent Advances in Micro- and Nano-Drug Delivery Systems Based on Natural and Synthetic Biomaterials.

Polymeric drug delivery technology, which allows for medicinal ingredients to enter a cell more easily, has advanced considerably in recent decades. Innovative medication delivery strategies use biodegradable and bio-reducible polymers, and progress in the field has been accelerated by future possible research applications. Natural polymers utilized in polymeric drug delivery systems include arginine, chitosan, dextrin, polysaccharides, poly(glycolic acid), poly(lactic acid), and hyaluronic acid. Additionally, poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable polymers, and bioabsorbable polymers as well as biomimetic and bio-related polymeric systems and drug-free macromolecular therapies have been employed in polymeric drug delivery. Different synthetic and natural biomaterials are in the clinical phase to mitigate different diseases. Drug delivery methods using natural and synthetic polymers are becoming increasingly common in the pharmaceutical industry, with biocompatible and bio-related copolymers and dendrimers having helped cure cancer as drug delivery systems. This review discusses all the above components and how, by combining synthetic and biological approaches, micro- and nano-drug delivery systems can result in revolutionary polymeric drug and gene delivery devices.

Thermo-Responsive Polyion Complex of Polysulfobetaine and a Cationic Surfactant in Water.

Poly(4-((3-methacrylamidopropyl)dimethylammonium)butane-1-sulfonate) (PSBP) was prepared via controlled radical polymerization. PSBP showed upper critical solution temperature (UCST) behavior in aqueous solutions, which could be controlled by adjusting the polymer and NaCl concentrations. Owing to its pendant sulfonate anions, PSBP exhibited a negative zeta potential of -7.99 mV and formed a water-soluble ion complex with the cationic surfactant cetyltrimethylammonium bromide (CTAB) via attractive electrostatic interaction. A neutral PSBP/CTAB complex was formed under equimolar concentrations of the pendant sulfonate group in PSBP and the quaternary ammonium group in CTAB. Transmittance electron microscopic images revealed the spherical shape of the complex. The stoichiometrically neutral-charge PSBP/CTAB complex exhibited UCST behavior in aqueous solutions. Similar to PSBP, the phase transition temperature of the PSBP/CTAB complex could be tuned by modifying the polymer and NaCl concentrations. In 0.1 M aqueous solution, the PSBP/CTAB complex showed UCST behavior at a low complex concentration of 0.084 g/L, whereas PSBP did not exhibit UCST behavior at concentrations below 1.0 g/L. This observation suggests that the interaction between PSBP and CTAB in the complex was stronger than the interpolymer interaction of PSBP.

"Foam Marble" Stabilized with One Type of Polymer Particle.

There has been increasing interest in colloidal particles adsorbed at the air-water interface, which lead to stabilization of aqueous foams and liquid marbles. The wettability of the particles at the interface is known to play an important role in determining the type of air/water dispersed system. Foams are preferably formed using relatively hydrophilic particles, and liquid marbles tend to be formed using relatively hydrophobic particles. In this study, submicrometer-sized polystyrene particles carrying poly(N,N-diethylaminoethyl methacrylate) hairs (PDEA-PS particles), which are synthesized by dispersion polymerization, are demonstrated to work as a particulate stabilizer for both aqueous foams and liquid marbles. A key point for the hydrophilic PDEA-PS particles to stabilize both aqueous foams and liquid marbles, which have been generally stabilized with hydrophilic and hydrophobic particles, respectively, is the wetting mode of the particles with respect to water. The flocculates of PDEA-PS particles adsorb to the air-water interface from the aqueous phase to stabilize foam in a Wenzel mode, and the dried PDEA-PS particles adsorb to the interface as aggregates from the air phase to stabilize liquid marbles in a metastable Cassie-Baxter mode. On the basis of the difference in the wetting mode, stabilization of an air-in-water-in-air multiple gas-liquid dispersed system, named "foam marble", is realized. After the evaporation of water from the foam marble, a porous sphere is successfully obtained with pore sizes of a few tens of micrometers (reflecting the bubble sizes) and a few tens of nanometers (reflecting the gap sizes among the PDEA-PS particles).

pH- and Thermo-Responsive Water-Soluble Smart Polyion Complex (PIC) Vesicle with Polyampholyte Shells.

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.

Association Behavior of Amphiphilic ABA Triblock Copolymer Composed of Poly(2-methoxyethyl acrylate) (A) and Poly(ethylene oxide) (B) in Aqueous Solution.

Poly(2-methoxyethyl acrylate) (PMEA) and poly(ethylene oxide) (PEO) have protein-antifouling properties and blood compatibility. ABA triblock copolymers (PMEAl-PEO11340-PMEAm (MEOMn; n is average value of l and m)) were prepared using single-electron transfer-living radical polymerization (SET-LRP) using a bifunctional PEO macroinitiator. Two types of MEOMn composed of PMEA blocks with degrees of polymerization (DP = n) of 85 and 777 were prepared using the same PEO macroinitiator. MEOMn formed flower micelles with a hydrophobic PMEA (A) core and hydrophilic PEO (B) loop shells in diluted water with a similar appearance to petals. The hydrodynamic radii of MEOM85 and MEOM777 were 151 and 108 nm, respectively. The PMEA block with a large DP formed a tightly packed core. The aggregation number (Nagg) of the PMEA block in a single flower micelle for MEOM85 and MEOM777 was 156 and 164, respectively, which were estimated using a light scattering technique. The critical micelle concentrations (CMCs) for MEOM85 and MEOM777 were 0.01 and 0.002 g/L, respectively, as determined by the light scattering intensity and fluorescence probe techniques. The size, Nagg, and CMC for MEOM85 and MEOM777 were almost the same independent of hydrophobic DP of the PMEA block.

Monitoring of Anticoagulant Activity of Dabigatran and Rivaroxaban in the Presence of Heparins.

The routine monitoring of direct oral anticoagulants (DOACs) may be considered in patients with renal impairment, patients who are heavily obese, or patients requiring elective surgery. Using the heparin-binding copolymer (HBC) and polybrene, we aimed to develop a solution for monitoring the anticoagulant activity of DOACs in human plasma in the interfering presence of unfractionated heparin (UFH) and enoxaparin. The thrombin time (TT) and anti-factor Xa activity were monitored in pooled plasma from healthy volunteers. In these tests, plasma with dabigatran or rivaroxaban was mixed with UFH or enoxaparin and then incubated with HBC or polybrene, respectively. HBC and polybrene neutralized heparins and enabled monitoring of anticoagulant activity of dabigatran in the TT test. Both agents allowed for accurate measurement of anti-factor Xa activity in the plasma containing rivaroxaban and heparins in the concentration range reached in patients' blood. Here, we present diagnostic tools that may improve the control of anticoagulation by eliminating the contamination of blood samples with heparins and enabling the monitoring of DOACs' activity.

Formation of Water-Soluble Complexes from Fullerene with Biocompatible Block Copolymers Bearing Pendant Glucose and Phosphorylcholine.

Double-hydrophilic diblock copolymers, PMPC100-block-PGEMAn (M100Gn), were synthesized via reversible addition-fragmentation chain transfer radical polymerization using glycosyloxyethyl methacrylate and 2-(methacryloyloxy)ethyl phosphorylcholine. The degree of polymerization (DP) of the poly(2-(methacryloyloxy) ethylphosphorylcholine) (PMPC) block was 100, whereas the DPs (n) of the poly(glycosyloxyethyl methacrylate) PGEMA block were 18, 48, and 90. Water-soluble complexes of C70/M100Gn and fullerene (C70) were prepared by grinding M100Gn and C70 powders in a mortar and adding phosphate-buffered saline (PBS) solution. PMPC can form a water-soluble complex with hydrophobic C70 using the same method. Therefore, the C70/M100Gn complexes have a core-shell micelle-like particle structure possessing a C70/PMPC core and PGEMA shells. The maximum amounts of solubilization of C70 in PBS solutions using 2 g/L each of M100G18, M100G48, and M100G90 were 0.518, 0.358, and 0.257 g/L, respectively. The hydrodynamic radius (Rh) of C70/M100Gn in PBS solutions was 55-75 nm. Spherical aggregates with a similar size to the Rh were observed by transmission electron microscopy. When the C70/M100Gn PBS solutions were irradiated with visible light, singlet oxygen was generated from C70 in the core. It is expected that the C70/M100Gn complexes can be applied to photosensitizers for photodynamic therapy treatments.

Preparation of Biocompatible Poly(2-(methacryloyloxy)ethyl phosphorylcholine) Hollow Particles Using Silica Particles as a Template.

Hydrophilic poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) shows biocompatibility because the pendant phosphorylcholine group has the same chemical structure as the hydrophilic part of phospholipids that form cell membranes. Hollow particles can be used in various fields, such as a carrier in drug delivery systems because they can encapsulate hydrophilic drugs. In this study, vinyl group-decorated silica particles with a radius of 150 nm were covered with cross-linked PMPC based on the graft-through method. The radius of PMPC-coated silica particles increased compared to that of the original silica particles. The PMPC-coated silica particles were immersed in a hydrogen fluoride aqueous solution to remove template silica particles to prepare the hollow particles. The PMPC hollow particles were characterized by dynamic light scattering, infrared spectroscopy, thermogravimetric analysis, and transmission electron microscopy observations. The thickness of the hollow particle shell can be controlled by the polymerization solvent quality. When a poor solvent for PMPC was used for the polymerization, PMPC hollow particles with thick shells can be obtained. The PMPC hollow particles can encapsulate hydrophilic guest molecules by immersing the hollow particles in a high-concentration guest molecule solution. The biocompatible PMPC hollow particles can be used in a drug carrier.

Self-Organized Nanoparticles of Random and Block Copolymers of Sodium 2-(Acrylamido)-2-methyl-1-propanesulfonate and Sodium 11-(Acrylamido)undecanoate as Safe and Effective Zika Virus Inhibitors.

A series of anionic homopolymers, poly(sodium 2-(acrylamido)-2-methyl-1-propanesulfonate) (PAMPS) and amphiphilic copolymers of AMPS and sodium 11-(acrylamido)undecanoate (AaU), both block (PAMPS75-b-PAaUn), and random (P(AMPSm-co-AaUn)), were synthesized and their antiviral activity against Zika virus (ZIKV) was evaluated. Interestingly, while the homopolymers showed limited antiviral activity, the copolymers are very efficient antivirals. This observation was explained considering that under the conditions relevant to the biological experiments (pH 7.4 PBS buffer) the macromolecules of these copolymers exist as negatively charged (zeta potential about -25 mV) nanoparticles (4-12 nm) due to their self-organization. They inhibit the ZIKV replication cycle by binding to the cell surface and thereby blocking virus attachment to host cells. Considering good solubility in aqueous media, low toxicity, and high selectivity index (SI) of the PAMPS-b-PAaU copolymers, they can be considered promising agents against ZIKV infections.