Poly Block Copolymers Research Articles

Bio-inspired nanoporous scaffold: electrospun hybrid fibers based on self-assembled block copolymer mineralized with inorganic nanoparticles for bone tissue engineering

Mineralized, bio-inspired nanofibrous scaffolds with controllable architecture and capable of mimicking essential characteristics of bone extracellular matrix at the micro- and nanoscale offer a promising strategy to restore functions or elicit favorable responses for bone tissue regeneration and repair. In this study, a simple approach to fabricate a hybrid scaffold with porous fibers for bone tissue engineering is presented. Non-woven multifunctional nano- and microfibers were fabricated using a block copolymer of poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) (PL-b-CL) as a matrix and hydroxyapatite (HA) as a functional agent, dissolved in a binary solvent mixture. Physicochemical and thermal characterization as well as biocompatibility analyses were carried out using SaOS-2 cells. The results showed fibers with highly porous surfaces whose pore diameters range in the nanometer scale and all scaffolds exhibited hydrophobicity. HA-modified scaffolds significantly improved cell metabolic activity and proliferation as compared to pristine scaffolds. The biodegradable and biocompatible scaffolds proposed in this study carry great potential for various biomedical applications and in the future, it is expected that they can be used for controlled drug delivery by incorporating growth factors, proteins, or drugs to reduce the inflammatory response and/or to promote bone repair.

In Situ and Ex Situ Studies of Ring-Like Assembly of Silica Nanoparticles in the Presence of Poly(propylene oxide)-Poly(ethylene oxide) Block Copolymers.

Block copolymer-mediated self-assembly of colloidal nanoparticles has attracted great attention for fabricating various nanoparticle arrays. We have previously shown that silica nanoparticles (SNPs) assemble into ring-like nanostructures in the presence of temperature-responsive block copolymers poly[(2-ethoxyethyl vinyl ether)-block-(2-methoxyethyl vinyl ether)] (PEOVE-PMOVE) in an aqueous phase. The ring-like nanostructures formed within an aggregate of PEOVE-PMOVE when the temperature was increased to 45 °C, at which the polymer is amphiphilic. Herein, we report that SNPs assemble into ring-like nanostructures even with a different temperature-responsive, amphiphilic block copolymer poly(propylene oxide)-block-poly(ethylene oxide) (PPO-PEO) at 45 °C. Field-emission scanning electron microscopy for SNP assemblies that were spin-coated on a substrate indicated that SNP first assembled into chain-like nanostructures and then bent into closed loops over several days. In contrast, in situ small-angle X-ray diffraction measurements revealed the formation of SNP nanorings within 75 s at 45 °C in the liquid phase. These results indicated that ring-like assembly of SNPs occurs quickly in the liquid phase, but the slow formation of Si-O-Si bonds between SNPs leads to their structure being destroyed by spin-coating. Intriguingly, SNPs with a diameter of 15 nm form a well-defined nanoring structure, with five SNPs located at the vertex points of a regular pentagon. Additionally, small-angle neutron scattering, where the contrast of the solvent (a mixture of H2O and D2O) matches that of SNPs, clarified that SNPs are contained within the spherical micelle formed from PPO-PEO. This work offers a facile and versatile approach to preparing ring-like arrays from inorganic colloidal nanoparticles, leading to applications including sensing, catalysis, and nanoelectronics.

Rhodamine B-Conjugated Fluorescent Block Copolymer Micelles for Efficient Chlorambucil Delivery and Intracellular Imaging.

The clinical development of the anticancer drug chlorambucil (CHL) is limited by its low solubility in water, poor bioavailability, and off-target toxicity. Besides, another constraint for monitoring intracellular drug delivery is the non-fluorescent nature of CHL. Nanocarriers based on block copolymers of poly(ethylene glycol)/poly(ethylene oxide) (PEG/PEO) and poly(ε-caprolactone) (PCL) are an elegant choice for drug delivery applications due to their high biocompatibility and inherent biodegradability properties. Here, we have designed and prepared block copolymer micelles (BCM) containing CHL (BCM-CHL) from a block copolymer having fluorescent probe rhodamine B (RhB) end-groups to achieve efficient drug delivery and intracellular imaging. For this purpose, the previously reported tetraphenylethylene (TPE)-containing poly(ethylene oxide)-b-poly(ε-caprolactone) [TPE-(PEO-b-PCL)2] triblock copolymer was conjugated with RhB by a feasible and effective post-polymerization modification method. In addition, the block copolymer was obtained by a facile and efficient synthetic strategy of one-pot block copolymerization. The amphiphilicity of the resulting block copolymer TPE-(PEO-b-PCL-RhB)2 led to the spontaneous formation of micelles (BCM) in aqueous media and successful encapsulation of the hydrophobic anticancer drug CHL (CHL-BCM). Dynamic light scattering and transmission electron microscopy analyses of BCM and CHL-BCM revealed a favorable size (10-100 nm) for passive targeting of tumor tissues via the enhanced permeability and retention effect. The fluorescence emission spectrum (λex 315 nm) of BCM demonstrated Förster resonance energy transfer between TPE aggregates (donor) and RhB (acceptor). On the other hand, CHL-BCM revealed TPE monomer emission, which may be attributed to the π-π stacking interaction between TPE and CHL molecules. The in vitro drug release profile showed that CHL-BCM exhibits drug release in a sustained manner over 48 h. A cytotoxicity study proved the biocompatibility of BCM, while CHL-BCM revealed significant toxicity to cervical (HeLa) cancer cells. The inherent fluorescence of RhB in the block copolymer offered an opportunity to directly monitor the cellular uptake of the micelles by confocal laser scanning microscopy imaging. These results demonstrate the potential of these block copolymers as drug nanocarriers and as bioimaging probes for theranostic applications.

Next-Generation Reconfigurable Nanoantennas and Polarization of Light.

This study is aimed at the design, calibration, and development of a near-infrared (NIR) liquid crystal multifunctional automated optical polarimeter, which is aimed at the study and characterization of the polarimetric properties of polymer optical nanofilms. The characterization of these novel nanophotonic structures has been achieved, in terms of Mueller matrix and Stokes parameter analyses. The nanophotonic structures of this study consisted of (a) a matrix consisting of two different polymer domains, namely polybutadiene (PB) and polystyrene (PS), functionalized with gold nanoparticles; (b) cast and annealed Poly (styrene-b-methyl methacrylate) (PS-PMMA) diblock copolymers; (c) a matrix of a block copolymer (BCP) domain, PS-b-PMMA or Poly (styrene-block-methy methacrylate), functionalized with gold nanoparticles; and (d) different thicknesses of PS-b-P2VP diblock copolymer functionalized with gold nanoparticles. In all cases, backscattered infrared light was studied and related to the polarization figures-of-merit (FOM). The outcome of this study indicates that functionalized polymer nanomaterials, depending upon their structure and composition, exhibit promising optical characteristics, modulating and manipulating the polarimetric properties of light. The fabrication of technologically useful, tunable, conjugated polymer blends with an optimized refractive index, shape, size, spatial orientation, and arrangement would lead to the development of new nanoantennas and metasurfaces.

In Situ Encapsulation of Camptothecin by Self-Assembly of Poly(acrylic acid)-b-Poly(N-Isopropylacrylamide) and Chitosan for Controlled Drug Delivery.

Camptothecin (CPT) has been shown to exhibit anticancer activity against several cancers. Nevertheless, CPT is very hydrophobic with poor stability, and thus its medical application is limited. Therefore, various drug carriers have been exploited for effectively delivering CPT to the targeted cancer site. In this study, a dual pH/thermo-responsive block copolymer of poly(acrylic acid-b-N-isopropylacrylamide) (PAA-b-PNP) was synthesized and applied to encapsulate CPT. At temperatures above its cloud point, the block copolymer self-assembled to form nanoparticles (NPs) and in situ encapsulate CPT, owing to their hydrophobic interaction as evidenced by fluorescence spectrometry. Chitosan (CS) was further applied on the surface through the formation of a polyelectrolyte complex with PAA for improving biocompatibility. The average particle size and zeta potential of the developed PAA-b-PNP/CPT/CS NPs in a buffer solution were 168 nm and -30.6 mV, respectively. These NPs were still stable at least for 1 month. The PAA-b-PNP/CS NPs exhibited good biocompatibility toward NIH 3T3 cells. Moreover, they could protect the CPT at pH 2.0 with a very slow-release rate. At pH 6.0, these NPs could be internalized by Caco-2 cells, followed by intracellular release of the CPT. They became highly swollen at pH 7.4, and the released CPT was able to diffuse into the cells at higher intensity. Among several cancer cell lines, the highest cytotoxicity was observed for H460 cells. As a result, these environmentally-responsive NPs have the potential to be applied in oral administration.

19 nm‐Thick Grafted‐To Polymer Brushes onto Optimized Poly(Dopamine)‐Coated Surfaces

AbstractGrafting‐to polymer coatings are typically easy to apply, but the thickness of such coatings is typically limited to a few nanometers, which may hamper applications. This paper presents a grafting‐to coating approach that yields polymer brushes up to an unprecedented thickness of 19 nm. To this aim, an easy‐to‐apply poly(dopamine) (PDA) primer layer is optimized. PDA is an easy‐to‐apply, but highly complex and chemically not well understood primer layer. In this study, PDA is deposited on silicon substrates using several deposition protocols (pH 4–7 in presence of NaIO4, and from Tris solution at pH 8.5). The modified surfaces are characterized using X‐ray photoelectron spectroscopy, spectroscopic ellipsometry, static water contact angle measurements, and atomic force microscopy. Subsequently, block copolymers of poly(glycidyl methacrylate)20‐b‐poly(N‐isopropylacrylamide)n are attached onto the PDA films using a grafting‐to approach. The results indicate that the conditions of PDA deposition and the PDA film thickness strongly influence the stability and grafting efficiency of the block copolymers. PDA films deposited at pH 7 with NaIO4 are stable, and yield the most efficient grafting, with grafted polymer layers as thick as 19 nm. Polymer layers of such thickness are rarely achieved using grafting‐to procedures from solution.

Proteinosomes via Self-Assembly of Thermoresponsive Miktoarm Polymer Protein Bioconjugates.

To fabricate nanoscale proteinosomes, thermoresponsive miktoarm polymer protein bioconjugates were prepared through highly efficient molecular recognition between the β-cyclodextrin modified BSA (CD-BSA) and the adamantyl group anchored at the junction point of the thermoresponsive block copolymer poly(ethylene glycol)-b-poly(di(ethylene glycol) methyl ether methacrylate) (PEG-b-PDEGMA). PEG-b-PDEGMA was synthesized by the Passerini reaction of benzaldehyde-modified PEG, 2-bromo-2-methylpropionic acid, and 1-isocyanoadamantane, followed by the atom transfer radical polymerization of DEGMA. Two block copolymers with different chain lengths of PDEGMA were prepared, and both self-assembled into polymersomes at a temperature above their lower critical solution temperatures (LCST). The two copolymers can undergo molecular recognition with the CD-BSA and form miktoarm star-like bioconjugates. The bioconjugates self-assembled into ∼160 nm proteinosomes at a temperature above their LCSTs, and the miktoarm star-like structure has a great effect on the formation of the proteinosomes. Most of the secondary structure and esterase activity of BSA in the proteinosomes were maintained. The proteinosomes exhibited low toxicity to the 4T1 cells and could deliver model drug doxorubicin into the 4T1 cells.

Polymeric assembled nanoparticles through kinetic stabilization by confined impingement jets dilution mixer for fluorescence switching imaging

• Rapidly-assembled nanoparticles prepared by flash nanoprecipitation. • Nanoparticles with controllable size and fluorescence intensity. • Fluorescence switching behavior under visible lights. Traditional fluorescence switching molecules achieving the state change between on and off states commonly based on UV irradiation. However, it is worth noting that UV irradiation is harmful to both the cancer cells and the normal cells. To achieve fluorescence switching under visible wavelength and avoid complicate molecular design, a fluorophore of 2,4,5,6-tetrakis(carbazol-9-yl)-1,3-dicyanobenzene (4CzIPN) and a quencher of diarylethene (DAE) were physically incorporated within the biocompatible block copolymer poly(lactic-co-glycolic acid)- b -poly(ethylene glycol) (PLGA- b -PEG) to form 4CzIPN-DAE nanoparticles (NPs) through flash nanoprecipitation (FNP). By using the FNP method, the NPs were prepared within milliseconds in a confined impingement jets dilution (CIJ-D) mixer. Quenching and recovery of fluorescence could achieve in the presence of DAE under 475 nm and 560 nm irradiation. Appropriate structure and fluorescent properties of the nanoparticles can be tuned by external conditions for their efficient fluorescence resonance energy transfer (FRET) in a kinetic stabilization process. This NPs formation process was further optimized by varying the dilution ratio, Reynolds number ( Re ) and polymer concentration to modulate the mixing and particle nucleation and growth process. The size and fluorescence switching properties of the NPs were systematically investigated in solution and in cellular uptake experiments. This work is anticipated to provide a simple and highly effective engineering strategy for the modulation of fluorescence switching nanoparticles and beneficial to its engineering application.

Complexes of Charged-Neutral Block Copolymers and Surfactants: Process-Dependent Features and Long-Term Stability of Their Aqueous Dispersions

Aqueous dispersions of charged-neutral block copolymers (poly(acrylamide)-b-poly(acrylate)) complexed with an oppositely charged surfactant (dodecyltrimethylammonium) have been prepared by different approaches: the simple mixing of two solutions (MS approach) containing the block copolymer and surfactant, with their respective simple counterions, and dispersion of a freeze-dried complex salt prepared in the absence of simple counterions (CS approach). The CS particles were investigated under different conditions: dispersion of a CS in salt-free water and dispersion of a CS in a dilute salt solution, the latter condition yielding dispersions with the same composition as the MS process. Additionally, aged dispersions (up to 6 months) and dispersed complexes of the polyacrylate homopolymer and dodecyltrimethylammonium surfactant were evaluated. By employing different characterization techniques, it was seen that dispersions prepared by the MS approach display nanometric spherical particles with disordered cores, and poor colloidal stability, partially caused by the absence of surface charge (ζ-potential close to zero). Oppositely, anisometric particles were formed in CS dispersions and were large enough to sustain micellar cubic cores. The CS particles presented long-time colloidal stability, partially due to a net negative surface charge, but the stability varied with the length of the neutral block composing the corona. Our results demonstrate that all dispersed particles are metastable structures, with physicochemical properties strongly dependent on the preparation procedure, thus making these particles suitable for fundamental studies and potential applications where accurate control of their properties, including size, shape, internal structure, and stability, is desired.

Immune Response to the Introduction of Fibrillogenic β2-Microglobulin Protein Conjugated with Different Types of Polymer Particles

The effect of the composition and size of polymeric particles on the immunogenicity of the fibrillogenic β2-microglobulin protein immobilized on their surface was studied. For this purpose, nanoparticles (NP) based on a copolymer of L-glutamic acid and L-phenylalanine (P(Glu-co-Phe)) and a block copolymer of poly(ethylene glycol) with poly(lactic acid) (PEG-b-PLA) as well as microparticles (MP) based on poly(lactic acid) (PLA) were selected. α-L-amino acid copolymer-based nanoparticles were prepared by gradient phase inversion, and PEG-b-PLA-based nanoparticles by nanoprecipitation. Double emulsion method was used to form polymeric microparticles based on PLA. Recombinant chimeric model protein beta-2-microglobulin-green fluorescent protein (β2M-sfGFP) was used to covalently modify all types of polymeric particles followed by immunization of four groups of laboratory animals equal in number. An enzyme immunoassay method was used to evaluate the humoral immune response. In three experimental groups, mice were immunized using poly(amino acid)-based nanoparticles (NP-PAA) and PEG-b-PMC (NP-PLA) as well as PLA microparticles containing immobilized β2M-sfGFP on the surface. The control group was immunized using a physical mixture of PEG-b-PLA nanoparticles and free β2M-sfGFP. The highest level of antibodies to sfGFP in blood serum was found when mice were immunized with a mixture of protein and nanoparticles. When mice were immunized with β2M-sfGFP-modified nanoparticles, the amount of antibodies to sfGFP was statistically significantly lower (p0.001) compared to the control group. However, the groups immunized with nanoparticles of similar size but different composition conjugated to the model proteins did not differ significantly among themselves. It was also found that the size of the particles affects the immunogenicity of the associated protein. A similar pattern of relative antibody content in the sera of mice was maintained at all steps of immunization.

Short-chain fatty acid-releasing nano-prodrugs for attenuating growth and metastasis of melanoma.

Low-molecular-weight (LMW) short-chain fatty acids (SCFAs), such as propionic and butyric acids, have been reported to possess anti-neoplastic effects; however, rapid renal clearance and high dose-based side effects limit their clinical translation. Hence, in this study, we have designed a new self-assembling nano-prodrugs that can effectively supply SCFAs: endogenous enzyme-metabolizable block copolymer poly(ethylene glycol)block-poly(vinyl ester) possessing several units of SCFAs conjugated as side chains via ester linkages. These amphiphilic polymers spontaneously self-assemble into nanostructures under aqueous conditions to form orally administrable nano-prodrugs (butyric acid: NanoBA and propionic acid: NanoPA). Herein, we show the therapeutic efficacy of SCFA nanoparticles (NanoSCFA) in a mouse model of metastasis (melanoma). Ad libitum intake of our NanoSCFA markedly demonstrated a decrease in the metastatic tumor nodules in the lungs compared with the effect observed after LMW SCFA administration with no discernible toxicity to the GI tract. In contrast, LMW SCFAs, even at a lower concentration than that of the NanoSCFA, facilitated villus atrophy. Taken together, our work suggests that the use of NanoSCFA as a therapeutic intervention for metastatic cancer is preferable over typical LMW SCFAs. STATEMENT OF SIGNIFICANCE: Low-molecular-weight (LMW) short-chain fatty acids (SCFAs) have shown versatile therapeutic effects on various diseases, including anti-tumorigenesis effects. However, their clinical translation is limited due to their poor pharmacokinetic profile and adverse effects. To overcome these limitations, we have developed new amphiphilic block copolymer-based SCFA-prodrugs, which self-assemble into nanoparticles in aqueous media (NanoSCFA). SCFAs are covalently conjugated to the hydrophobic polymer segment via ester linkage, which can be enzymatically metabolized after oral administration. In the present study, we confirmed that ad libitum intake of NanoSCFAs retarded the growth and metastatic potential of B16-F10 tumors compared to the LMW SCFAs with negligible discernible toxicity, reflecting NanoSCFA as a preferable therapeutic intervention to LMW SCFA counterparts.

Construction of micro/macro‐scale Janus polypeptoid‐based two‐dimensional structures at the air–water interface

AbstractJanus two‐dimensional (2D) polymeric materials present asymmetric dual surfaces that enable a variety of applications of biosensors, catalysts, drug delivery, etc. This work reports the evaporation‐induced interfacial self‐assembly of amphiphilic block copolymer poly(ethylene glycol)‐b‐poly(N‐(2‐phenylethyl) glycine) (PEG‐b‐PNPE) at the air–water interface. The PEG‐b‐PNPE was initially assembled into a monolayer with a uniform thickness of ~2.5 ± 0.1 nm, which was mechanically compressed into a bilayer structure by Langmuir–Blodgett (LB) technology as surface pressure is exceeding the critical collapse pressure. Both monolayer and bilayer nanostructure span over hundreds of microns in both dimensions. The surface contact angle of the sample was measured by dynamic/static optical contact angle/interface tensiometer, which showed asymmetric wettability on the air side and the water side. The evolution from a monolayer to a bilayer was further tracked by an atomic force microscope. By the evaporation‐induced interfacial self‐assembly at the air–water interface, we also prepared macroscopic Janus films with a diameter of ~3.5 mm. The obtained micro/macro‐scale 2D materials have potential applications in nanoscience and biomedicine.

Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy.

Glioblastoma (GBM) is one of the most lethal malignancies with poor survival and high recurrence rates. Here, we aimed to simultaneously target oncomiRs 10b and 21, reported to drive GBM progression and invasiveness. We designed short (8-mer) γ-modified peptide nucleic acids (sγPNAs), targeting the seed region of oncomiRs 10b and 21. We entrapped these anti-miR sγPNAs in nanoparticles (NPs) formed from a block copolymer of poly(lactic acid) and hyperbranched polyglycerol (PLA-HPG). The surface of the NPs was functionalized with aldehydes to produce bioadhesive NPs (BNPs) with superior transfection efficiency and tropism for tumor cells. When combined with temozolomide, sγPNA BNPs administered via convection-enhanced delivery (CED) markedly increased the survival (>120 days) of two orthotopic (intracranial) mouse models of GBM. Hence, we established that BNPs loaded with anti-seed sγPNAs targeting multiple oncomiRs are a promising approach to improve the treatment of GBM, with a potential to personalize treatment based on tumor-specific oncomiRs.

Novel Aggregation-Induced Emission Fluorescent Molecule for Platinum(IV) Ion-Selective Recognition and Imaging of Controlled Release in Cells.

The loading, delivery, and release of Pt(IV) precursors in living organisms are important aspects of exploring the development of platinum drugs. In recent years, the biological application of the fluorescent sensors to platinum drugs has been insufficient to meet the study of Pt(IV) precursors. It is urgent to design and develop a biocompatible, multifunctional fluorescent sensor for the study of loading, transport, and release of Pt(IV) ions. Herein, we report a fluorescent molecule (E)-6-(diethylamino)-N'-(4-(diphenylamino) benzylidene)-2-oxo-2H-chromene-3 carbohydrazide (CHTPA). CHTPA has good sensitivity and selectivity to Pt(IV) when the water content is 5%, and significant increase of the fluorescence emission intensity of CHTPA is observed with Pt(IV) concentration. The sensing mechanism is attributed to photo-induced electron transfer, which is verified by X-ray absorption near edge spectroscopy spectra, UV-vis absorption spectroscopy, 1H NMR spectra, and Fourier transform infrared spectra. Furthermore, the CHTPA-Pt(IV) complex is able to release Pt(IV) in aqueous solution, and the green fluorescence of CHTPA based on the aggregation-induced emission effect can be observed. Inspired by these, the amphiphilic block copolymer poly(ethyloxide)-block-polystyrene (PEO-b-PS) is used to prepare the nonconjugated polymer dots (Pdots). The experimental results show that Pdots can effectively slow down the release speed of Pt(IV) in aqueous solution and it has a great monodispersity in aqueous solution. Meanwhile, Pdots show low cytotoxicity, and this is favorable for intracellular applications. The investigation of cellular imaging indicates that these Pdots can act as a carrier to deliver Pt(IV) into MCF-7 cells for visualized delivery and sustained release of platinum(IV) ions. Therefore, this study provides a new avenue to design and develop a biocompatible multifunctional fluorescent sensor for studying the loading, delivery, and release of Pt(IV) in cells.

Synthesis & characterization of amino acid-based acrylamide derived amphiphilic block copolymer using a new xanthate and its influence on cell cytotoxicity & cell viability

The development of amino acid-based polymers was due to their unique properties and structures like of biocompatible polymers having sensitive effects for numerous medicinal and biological actions like biochemical sensing and controlled release of drugs. To achieve this, poly (N-vinylpyrrolidone) (PNVP) and its block copolymer poly (N-vinylpyrrolidone)-b-poly (N-acryloyl-L-phenylalanine) (PNVP-b-PNALP) were synthesized by using a xanthate i.e., ethyl 2-((isopropoxycarbonothioyl)thio)-2-methylpropanoate (IPX), which exhibits good control RAFT polymerization. The plot between molar mass and conversion yields a linear line which confirms the pseudo-first-order kinetics, and molar mass distribution (Ðm) was found between (1.50–1.24). Both polymers were characterized by 1H NMR, FTIR, DSC, TGA-DTA, GPC, and XRD analysis. TEM and DLS study of the aqueous solution of the block copolymer (PNVP-b-PNALP) exhibited self-assembly (119–160 nm with a few smaller particles of 91 nm). Different concentrations of polymers (200–0.75 μM) were evaluated for their toxicities on macrophages (RAW 264.7) and cancer (MCF7) cell lines. The polymers were found to be nontoxic as we did not observe any significant changes in the rate of proliferation of both cells even at higher concentrations (up to 100 μM). However, the polymers were found to induce apoptosis-like changes in the cancer cells up to 100 μM, albeit not significant.

The Novel Gallium Aminobisphenolate Initiator of the Ring-Opening Copolymerization of L-Lactide and ε-Caprolactone: A Computational Study.

Density functional theory (DFT) simulations of ring-opening copolymerization of ε-caprolactone (CL) and L-lactide (LA) in presence of novel gallium complex on aminobis (phenolate) ligand are conducted. The initial steps of polymerization of CL and LA as well as the first steps of propagation which led to LGa-LA-LA-OMe, LGa-LA-CL-OMe, LGa-CL-LA-OMe, or LGa-CL-CL-OMe derivatives have been analyzed in detail. According to these data, the studied catalyst is a rare example of a catalyst in which, during copolymerization, the polymerization of CL should proceed faster than LA. Thus, we predict the formation of a mainly block copolymer poly(CL-block-LA) using this catalyst.

Reactive Oxygen Species-Responsive Polypeptide Drug Delivery System Targeted Activated Hepatic Stellate Cells to Ameliorate Liver Fibrosis.

Hepatic fibrosis is a chronic liver disease that lacks effective pharmacotherapeutic treatments. As part of the disease's mechanism, hepatic stellate cells (HSCs) are activated by damage-related stimuli to secrete excessive extracellular matrix, leading to collagen deposition. Currently, the drug delivery system that targets HSCs in the treatment of liver fibrosis remains an urgent challenge due to the poor controllability of drug release. Since the level of reactive oxygen species (ROS) increases sharply in activated HSCs (aHSCs), we designed ROS-responsive micelles for the HSC-specific delivery of a traditional Chinese medicine, resveratrol (RES), for treatment of liver fibrosis. The micelles were prepared by the ROS-responsive amphiphilic block copolymer poly(l-methionine-block-Nε-trifluoro-acetyl-l-lysine) (PMK) and a PEG shell modified with a CRGD peptide insertion. The CRGD-targeted and ROS-responsive micelles (CRGD-PMK-MCs) could target aHSCs and control the release of RES under conditions of high intracellular ROS in aHSCs. The CRGD-PMK-MCs treatment specifically enhanced the targeted delivery of RES to aHSCs both in vitro and in vivo. In vitro experiments show that CRGD-PMK-MCs could significantly promote ROS consumption, reduce collagen accumulation, and avert activation of aHSCs. In vivo results demonstrate that CRGD-PMK-MCs could alleviate inflammatory infiltration, prevent fibrosis, and protect hepatocytes from damage in fibrotic mice. In conclusion, CRGD-PMK-MCs show great potential for targeted and ROS-responsive controlled drug release in the aHSCs of liver fibrosis.

Properties in Langmuir Monolayers and Langmuir-Blodgett Films of a Block Copolymer Based on N-Isopropylacrylamide and 2,2,3,3-Tetrafluropropyl Methacrylate

The amphiphilic block copolymer poly(N-isopropylacrylamide)-Ge(C6F5)2-poly(2,2,3,3-tetrafluoropropyl methacrylate) was prepared by the reaction of chain transfer to bis-(pentafluorophenyl)germane during the polymerization of N-isopropylacrylamide and the subsequent postpolymerization of isolated functional polymers in 2,2,3,3-tetrafluoropropyl methacrylate. The conversion of the block copolymer was 68% and the molecular weight of the sample was 490,000 g/mol. The colloidal chemical properties of Langmuir monolayers and Langmuir-Blodgett films of synthesized block copolymer have been studied. For comparison, a functional polymer, namely, poly-N-isopropylacrylamide with terminal -Ge(C6F5)2H group, was synthesized and studied. The concentrations of spreading solutions were selected and the effect of subphase acidity on the formation of monolayers of macromolecules of the block copolymer was studied. It was found that regardless of the acidity of the subphase, high pressure of fracture of films are characteristic of monolayers of collapse pressures πmax = (48-61) mN/m. The morphology of the Langmuir-Blodgett films of functional polymer exhibit isolated elongated micelles with high densities in the form of "octopus" on the periphery of which there are terminal hydrophobic groups. For the Langmuir-Blodgett film of block copolymer, a comb-like structure is observed with characteristic protrusions.

Visible light-induced radical polymerization of vinyl acetate mediated by organo-nickel N2O2 Schiff-base complexes

Four nickel(II) complexes with symmetrically substituted N2O2 tetradentate Schiff-base ligands, prepared from the 2:1 condensation of 3-tert-butyl-salicylaldehyde, and ethylenediamine (1), o-phenylenediamine (2), 1,2-cis,trans-cyclohexyldiamine (3), or 1,3-diaminepropane (4), were synthesized. These NiII Schiff-base complexes (1–4) were used as control agents for the polymerization of vinyl acetate (VAc) photoinitiated by diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO) according to a photoinduced organometallic-mediated radical polymerization (photo-OMRP) mechanism. All complexes presented good control ability, although the polymerization mediated by 3 showed the best control over molecular weight (Mn matching Mn,th) and dispersity (Ð < 1.50). The livingness of the polymers has been confirmed by LED on and LED off experiments, the polymerization stopped immediately, and no monomer conversion was observed during the light-off period, indicating a negligible concentration of the active radical in the dark. Further, to demonstrate the living nature of this system, block copolymers of poly(vinyl acetate)-b-poly(methyl acrylate) were synthesized using the sequential visible-light-induced process. Kinetic results and computational investigations supported the activation/deactivation equilibrium exerted by complexes 1–4, which occurred on only one face of the complexes via reversible deactivation (RD) mechanism.

Nanomedicines Bearing an Alkylating Cytostatic Drug from the Group of 1,3,5-Triazine Derivatives: Development and Characterization.

Cancer is still one of the major diseases worldwide. The discovery of new drugs and the improvement of existing ones is one of the areas of priority in the fight against cancer. Dioxadet ([5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol) represents one of the promising 1,3,5-triazine derivatives and has cytostatic activity towards ovarian cancer. In this study, we first report the development of dioxadet-bearing nanomedicines based on block-copolymers of poly(ethylene glycol) monomethyl ether (mPEG) and poly(D,L-lactic acid) (PLA)/poly(ε-caprolactone) (PCL) and then conduct an investigation into their characteristics and properties. The preparation of narrow-sized nanoparticles with a hydrodynamic diameter of 100-120 nm was optimized using a nanoprecipitation approach. Thoughtful optimization of the preparation of nanomedicines was carried out through adjustments to the polymer's molecular weight, the pH of the aqueous medium used for nanoprecipitation, the initial drug amount in respect to the polymer, and polymer concentration in the organic phase. Under optimized conditions, spherical-shaped nanomedicines with a hydrodynamic diameter of up to 230 nm (PDI &lt; 0.2) containing up to 592 ± 22 μg of dioxadet per mg of polymer nanoparticles were prepared. Study of the drug's release in a model medium revealed the release up to 64% and 46% of the drug after 8 days for mPEG-b-PLA and mPEG-b-PCL, respectively. Deep analysis of the release mechanisms was carried out with the use of a number of mathematical models. The developed nanoparticles were non-toxic towards both normal (CHO-K1) and cancer (A2780 and SK-OV-3) ovarian cells. A cell cycle study revealed lesser toxicity of nanomedicines towards normal cells and increased toxicity towards cancer cells. The IC50 values determined for dioxadet nanoformulations were in the range of 0.47-4.98 μg/mL for cancer cells, which is close to the free drug's efficacy (2.60-4.14 μg/mL). The highest cytotoxic effect was found for dioxadet loaded to mPEG-b-PCL nanoparticles.