Acid Block Copolymer Research Articles

Angiopoietin-1 Mimetic Nanoparticles for Restoring the Function of Endothelial Cells as Potential Therapeutic for Glaucoma.

A root cause for the development and progression of primary open-angle glaucoma might be the loss of the Schlemm’s canal (SC) cell function due to an impaired Angiopoietin-1 (Angpt-1)/Tie2 signaling. Current therapeutic options fail to restore the SC cell function. We propose Angpt-1 mimetic nanoparticles (NPs) that are intended to bind in a multivalent manner to the Tie2 receptor for successful receptor activation. To this end, an Angpt-1 mimetic peptide was coupled to a poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) block co-polymer. The modified polymer allowed for the fabrication of Angpt-1 mimetic NPs with a narrow size distribution (polydispersity index < 0.2) and the size of the NPs ranging from about 120 nm (100% ligand density) to about 100 nm (5% ligand density). NP interaction with endothelial cells (HUVECs, EA.hy926) as surrogate for SC cells and fibroblasts as control was investigated by flow cytometry and confocal microscopy. The NP–cell interaction strongly depended on the ligand density and size of NPs. The cellular response to the NPs was investigated by a Ca2+ mobilization assay as well as by a real-time RT-PCR and Western blot analysis of endothelial nitric oxide synthase (eNOS). NPs with a ligand density of 25% opposed VEGF-induced Ca2+ influx in HUVECs significantly which could possibly increase cell relaxation and thus aqueous humor drainage, whereas the expression and synthesis of eNOS was not significantly altered. Therefore, we suggest Angpt-1 mimetic NPs as a first step towards a causative therapy to recover the loss of SC cell function during glaucoma.

Defining Swelling Kinetics in Block Copolymer Thin Films: The Critical Role of Temperature and Vapour Pressure Ramp.

We studied the kinetics of swelling in high-χ lamellar-forming poly(styrene)-block- poly(lactic acid) (PS-b-PLA) block copolymer (BCP) by varying the heating rate and monitoring the solvent vapour pressure and the substrate temperature in situ during solvo-thermal vapour annealing (STVA) in an oven, and analysing the resulting morphology. Our results demonstrate that there is not only a solvent vapour pressure threshold (120 kPa), but also that the rate of reaching this pressure threshold has a significant effect on the microphase separation and the resulting morphologies. To study the heating rate effect, identical films were annealed in a tetrahydrofuran (THF) vapour environment under three different ramp regimes, low ), medium and high , for 60, 90 and 120 min, respectively, while the solvent vapour pressure and the substrate temperature were measured in real time. The translational order improved significantly with increasing the heating rate. The solvent mass uptake calculated for the different ramp regimes during annealing is linearly proportional to time, indicating that the swelling kinetics followed Case II diffusion. Two stages of the swelling behaviour were observed: (i) diffusion at the initial stages of swelling and (ii) stress relaxation, controlled at later stages. Films with a faster rate of increase in vapour pressure ) reached the pressure threshold value at an early stage of the swelling and attained a good phase separation. According to our results, highly ordered patterns are only obtained when the volume fraction of the solvent exceeds the polymer volume fraction, i.e., , during the swelling process, and below this threshold value , the films did not obtain a good structural order, even at longer annealing times.

Effect of Surface Silanol Density on the Proton Conductivity of Polymer-Surface-Functionalized Silica Nanoparticles

We have developed a polymer electrolyte membrane (PEM) material using polymer-coated silica nanoparticles (NPs) by the reversible addition-fragmentation chain-transfer polymerization with particles (RAFT PwP) method. In this paper, we controlled the number density of surface silanol groups on the silica NPs that not only maintain the structure of the surface adsorbed polymers by RAFT PwP but also form fast proton-conducting interface to study the silanol density effect on proton conductivity. The number of surface silanol groups was successfully increased by NaOH surface treatment and decreased by heat treatment. Then, we clarified that silanol-rich silica NPs with a polyacrylic acid and polystyrene block copolymer (PAA-b-PS) applied by RAFT PwP exhibit larger proton conductivity. This result implies that hydrophilicity of the filler is one of the important factors in the design of filler-functionalized PEM with high proton conductivity.

Polylactic acid block copolymer grafted temozolomide targeted nano delivery in the treatment of glioma

Gliomas are tumors of the central nervous system; they can be invasive and are commonly treated by surgical resection, chemo, and radiotherapy. Removal of a glioma is dangerous and not always successful. Temozolomide (TMZ), the first-line chemotherapy drug for gliomas, inhibit tumor recurrence, and metastasis to some extent. TMZ is often accompanied by side effects such as anemia, fever, constipation, and more. Here using a double-targeted Kunitz domain Angiopep-2 (ANG) modified block copolymer poly(lactic acid)-polyethylene glycol (PEG-PLA) coated with TMZ, we constructed a nano-delivery system (ANG@PLA-PEG/TMZ) that crosses the blood-brain barrier (BBB) to treat gliomas.

Preparation and In Vitro/Vivo Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery

Folate-conjugated Pluronic F87-poly(lactic-co-glycolic acid) block copolymer (FA-F87-PLGA) was synthesized to encapsulate anticancer drug Paclitaxel (PTX) for targeted drug delivery. To further improve the curative effect, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) was added to form FA-F87-PLGA/TPGS mixed NPs. FA-F87-PLGA was synthesized by the ring-opening polymerization and the structure was characterized. PTX-loaded nanoparticles were prepared with the nanoprecipitation method. The physicochemical characteristics were studied to determine the appropriate dose ratio of the FA-F87-PLGA to TPGS. The cytotoxicity against Ovarian Cancer Cells (OVCAR-3) was determined by MTT assay. The Area-Under-the Curve (AUC) and half-life were measured in the vivo pharmacokinetic studies. Based on the optimization of particle size and embedding rate of PTX-loaded mixed NPs, the appropriate dosage ratio of FA-F87-PLGA to TPGS was finally determined to be 5:3. According to in vitro release studies, the cumulative release rate of PTX-loaded FA-F87-PLGA/TPGS mixed NPs was 92.04%, which was higher than that of nanoparticles without TPGS. The cytotoxicity studies showed that the IC50 value of PTX-loaded FA-F87-PLGA/TPGS decreased by 75.4 times and 19.7 times after 72 h treatment compared with free PTX injections and PTX-loaded FA-F87-PLGA NPs, respectively. In vivo pharmacokinetic studies indicated that FA-F87-PLGA/TPGS mixed NPs had a longer drug metabolism time and a larger Area-Under-the-Curve (AUC) compared with free PTX injections. FA-F87-PLGA/TPGS mixed NPs are potential candidates for targeted drug delivery systems.

Size-controlled bimodal in vivo nanoprobes as near-infrared phosphors and positive contrast agents for magnetic resonance imaging

ABSTRACT Rare-earth-doped nanoparticles (NPs), such as NaGdF4 nanocrystals doped with light-emitting rare earth ions, are promising bimodal probes that allow the integration of over 1000 nm near-infrared (OTN-NIR; NIR-II/III) fluorescence imaging and magnetic resonance imaging (MRI) of live bodies. A precise control of the particle size is the key factor for achieving a high signal-to-noise ratio in both NIR fluorescence and MR images and for regulating their function in the body. In this study, size-controlled NaGdF4:Yb3+, Er3+ NPs prepared by stepwise crystal growth were used for in vivo bimodal imaging. Hexagonal NaGdF4:Yb3+,Er3+ NPs coated with poly(ethylene glycol)-poly(acrylic acid) block copolymer, with hydrodynamic diameters of 15 and 45 nm, were prepared and evaluated as bimodal NPs for OTN-NIR fluorescence imaging and MRI. Their longitudinal (T 1) and transverse (T 2) relaxation rates at the static magnetic field strength of 1.0 T, as well as their cytotoxicity towards NIH3T3 cell lines, were evaluated and compared to study the effect of size. Using these particles, blood vessel visualization was achieved by MRI, with the highest relaxometric ratio (r 1/r 2) of 0.79 reported to date for NaGdF4-based nanoprobes (r 1 = 19.78 mM−1 s−1), and by OTN-NIR fluorescence imaging. The results clearly demonstrate the potential of the size-controlled PEG-modified NaGdF4:Yb3+,Er3+ NPs as powerful ‘positive’ T 1-weight contrast MRI agents and OTN-NIR fluorophores.

Molecular tailoring of polystyrene-block-poly (acrylic acid) block copolymer toward additive-free asymmetric isoporous membranes via SNIPS

Polystyrene-block-poly (acrylic acid) (PS-b-PAA) diblock copolymers with different compositions were systematically synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization and used to prepare asymmetric isoporous membranes directly through self-assembly and nonsolvent induced phase separation (SNIPS) process, without using foreign additives. A simple and efficient way, for the first time, to generate additive-free asymmetric isoporous PS-b-PAA membranes was enabled just by choosing the right blocks composition. Dynamic light scattering (DLS) measurements at dilute concentrations and solution small angle X-ray scattering (solution SAXS) analysis plus rheological measurements in concentrated regime as well as field emission scanning electron microscopy (FE-SEM) were employed to investigate the relationship between properties of different block copolymer casting solutions and final membrane structures. DLS measurements and FE-SEM micrographs revealed that only micellar solutions with adequate micelle dimensions were able to produce membranes with more uniform surface pores. Micelles with short PS- lengths led to the formation of mesostructures with adequate structural characteristics in the casting solution, whereas rheological characteristics were the worst. A combination of both appropriate structural and rheological characteristics for the casting solution was necessary to achieve perfect membrane structures with ordered, high density and mono size-dispersed surface pores that all were dependent on PS/PAA blocks ratio. In addition to surface pores, membrane substructures were also influenced by the PS- block length. Sublayers with mostly finger-like structure along with higher permeability were obtained for the block copolymer with adequate PS- block length. Although dispersity (Ð) value of the synthesized block copolymers was acceptable (≤1.2) to form well-defined ordered isoporous structures, a slight difference in Ð had a decisive role on micellization, casting solution characteristics and final membrane structures. The most appropriate membrane structure showed a ≈150 nm thin selective-layer with ≈14 nm mean pore diameter and relatively high pore density of about 4 × 1014 pores/m2 at top surface, supported by the asymmetric substructure composed of a finger-like upper layer (66% of total thickness) and interconnected open pores at underneath. Considering its free-additive nature and high performances, these PS-b-PAA membranes are promising candidates for a wide range of size-based separation applications including biomedical and pharmaceutical industries.

RAFT polymerization mediated core-shell supramolecular assembly of PEGMA-co-stearic acid block co-polymer for efficient anticancer drug delivery.

In this work, core–shell supramolecular assembly polymeric nano-architectures containing hydrophilic and hydrophobic segments were synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization. Herein, polyethylene glycol methyl ether methacrylate (PEGMA), and stearic acid were used to synthesize the poly(PEGMA) homopolymer and stearyl ethyl methacrylate (SEMA), respectively. Then, PEGMA and SEMA were polymerized through controlled RAFT polymerization to obtain the final diblock copolymer, poly(PEGMA-co-SEMA) (BCP). Model anticancer drug, doxorubicin (DOX) was loaded on BCPs. Interestingly, efficient DOX release was observed at acidic pH, similar to the cancerous environment pH level. Significant cellular uptake of DOX loaded BCP50 (BCP50-DOX) was observed in MDA-MB-231 triple negative breast cancer cells and resulted in a 35 fold increase in anticancer activity against MDA MB-231 cells compared to free DOX. Scanning electron microscopy (SEM) imaging confirmed the apoptosis mediated cellular death. These core–shell supramolecular assembly polymeric nano-architectures may be an efficient anti-cancer drug delivery system in the future.

A New Approach to Developing Long-Acting Injectable Formulations of Anti-HIV Drugs: Poly(Ethylene Phosphoric Acid) Block Copolymers Increase the Efficiency of Tenofovir against HIV-1 in MT-4 Cells.

Despite the world’s combined efforts, human immunodeficiency virus (HIV), the causative agent of AIDS, remains one of the world’s most serious public health challenges. High genetic variability of HIV complicates the development of anti-HIV vaccine, and there is an actual clinical need for increasing the efficiency of anti-HIV drugs in terms of targeted delivery and controlled release. Tenofovir (TFV), a nucleotide-analog reverse transcriptase inhibitor, has gained wide acceptance as a drug for pre-exposure prophylaxis or treatment of HIV infection. In our study, we explored the potential of tenofovir disoproxil (TFD) adducts with block copolymers of poly(ethylene glycol) monomethyl ether and poly(ethylene phosphoric acid) (mPEG-b-PEPA) as candidates for developing a long-acting/controlled-release formulation of TFV. Two types of mPEG-b-PEPA with numbers of ethylene phosphoric acid (EPA) fragments of 13 and 49 were synthesized by catalytic ring-opening polymerization, and used for preparing four types of adducts with TFD. Antiviral activity of [mPEG-b-PEPA]TFD or tenofovir disoproxil fumarate (TDF) was evaluated using the model of experimental HIV infection in vitro (MT-4/HIV-1IIIB). Judging by the values of the selectivity index (SI), TFD exhibited an up to 14-fold higher anti-HIV activity in the form of mPEG-b-PEPA adducts, thus demonstrating significant promise for further development of long-acting/controlled-release injectable TFV formulations.

Iron chelation cancer therapy using hydrophilic block copolymers conjugated with deferoxamine.

Cancer cells have high iron requirements due to their rapid growth and proliferation. Iron depletion using iron chelators has a potential in cancer treatment. Previous studies have demonstrated that deferoxamine (DFO) specifically chelates Fe(III) and exhibited antitumor activity in clinical studies. However, its poor pharmacokinetics has limited the therapeutic potential and practical application. Although polymeric iron chelators have been developed to increase the blood retention, none of previous studies has demonstrated their potential in iron chelation cancer therapy. Here, we developed polymeric DFO by the covalent conjugation of DFO to poly(ethylene glycol)‐poly(aspartic acid) (PEG‐PAsp) block copolymers. The polymeric DFO exhibited iron‐chelating ability comparable with free DFO, thereby arresting cell cycle and inducing apoptosis and antiproliferative activity. After intravenous administration, the polymeric DFO showed marked increase in blood retention and tumor accumulation in subcutaneous tumor models. Consequently, polymeric DFO showed significant suppression of the tumor growth compared with free DFO. This study reveals the first success of the design of polymeric DFO for enhancing iron chelation cancer therapy.

Enhancing the specific T cell immune response against micro- and nanoparticle immobilized antigen

The current study was a part of the project on generating viral particle traps occurring due to covalent immobilization on the interface of recombinant virus-specific polymer-based nano- and microparticles. It is assumed that protein-particle conjugates could be able to bind virions followed by engulfment by immune cells. The study was aimed to examine the effect of polylactic acid (PLA) and PLA block-copolymer with polyethylene glycol (PLA-PEG)-based micro- and nanoparticles on the cellular immune response against polymeric particle-bound antigen. Materials and methods. A recombinant chimeric protein beta-2-microglobulin — green fluorescent protein (β2M-sfGFP) was obtained by affine chromatography. The recombinant protein was immobilized onto the polymer particles, which were further used for mice immunization. Female F1 hybrid mice (CBA x C57BL) in experimental and control groups consisted of 4–6-month-old 15 animals (weighted 20–25 g). Intracellular cytokine staining was used to evaluate the cellular immune response. Results and discussion. It was shown that the nanoparticles of PLA block-copolymer with polyethylene glycol (PLA-PEG) were able to bind 10 microgram protein per 1 mg polymer. The polylactic acid nanoparticles were able to bind 2,3 microgram protein per 1 mg polymer. In experiment, mice in group 1 were immunized with 100 nm PLA-PEG particle-β2M-sfGFP conjugate, in group 2 — with same particles together with soluble β2M-sfGFP. In group 3, mice were immunized with 1400 nm PLA particles-β2M-sfGFP conjugate, and in group 4 — with same particles together with soluble protein. The spleens isolated 2 weeks after the four-time intraperitoneal immunization. Comparison of immune response between groups was assessed by nonparametric Kruskal–Wallis criterion with Tukey correction. It was shown that the number of antigen-specific CD4+ T cells produced to model protein was significantly higher after immunization with particle-β2M-sfGFP conjugate, as compared to control groups, wherein immunization was performed with a mixture of protein and unmodified particles (p 0.001). It was found that the number of antigen-specific CD8+ T cells formed against β2m-sfGFP did not differ between all groups examined.

Targeted nano-sized drug design in cancer treatments: development of new nano-sized formulations for the use of anti-cancerogenic lisinopril in the treatment of colorectal cancer

Background: Colorectal cancer emerges as a serious health problem all over the world and results in approximately 700,000 deaths every year. Therefore, studies are carried out to develop alternative treatment methods to reduce the side effects of anticancer drugs in cancer treatment. Targeted nanoparticle therapies are tried to be developed especially with controlled drug release. Lisinopril, an angiotensin-converting enzyme inhibitor, is a widely used drug in the treatment of hypertension and has been shown to have anticancer activity on various types of cancer.Methods: This study, blank and 3 different amounts of lisinopril loaded nanoparticles were prepared by triblock poly (lactic acid)–poly (ethylene glycol)–poly (lactic acid) (PLA-PEG-PLA) block copolymer which is a biocompatible and biodegradable polymer by using water/oil/water emulsion method and then characterized. The viability of the blank formulations in murine fibroblast (L929) cells, which is the healthy cell line, was determined within the scope of biocompatibility studies.Results: The anticarcinogenic activity of lisinopril drug, blank and lisinopril loaded nanoparticles was determined in caco-2 cells which are human epithelial colorectal adenocarcinoma cell line.Conclusions: Lisinopril loaded nanoparticles were successfully prepared in this study. It is thought that increasing the amount of drug-loaded can be a promising approach to an alternative treatment method for the use of antihypertensive drugs in the treatment of colorectal cancer.

Photocatalytically active block copolymer hybrid micelles from double hydrophilic block copolymers

Herein, we demonstrate that double hydrophilic block copolymers can be used for the preparation of photocatalytically active organic/inorganic hybrid micelles. This is realized by immobilization of CdS nanoparticles for photocatalytic water splitting within well-defined poly(2-iso-propyl-2-oxazoline)-block-poly(2-acrylamido glycolic acid) (PiPrOx-b-PAGA) block copolymers. The prepared PiPrOx-b-PAGA/CdS hybrid nanostructures were characterized regarding morphology, structure, and optical properties by UV/Vis and photoluminescence (PL) spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). Our results confirm spherical inorganic-organic micelles containing ultra-small CdS nanoparticles with photoluminescent character within the core. Afterwards, these hybrid nanostructures were used for photocatalytic H2 production in the presence of triethanol amine (TEOA) as sacrificial reagent in water under visible-light illumination (λ ≥ 470 nm), revealing 18-fold increased activity compared to bare CdS nanoparticles. The enhanced photocatalytic activity can be attributed to several factors, such as 3D confinement within micellar nanostructures, the presence of ultra-small CdS nanoparticles, or an improved stability of CdS nanoparticles within the micellar core. Overall, we demonstrate that double hydrophilic BCP can be an interesting platform for the formation of photocatalytically active micellar nanostructures, leading to materials with potential relevance for photocatalysis.

Hydrolytic stabilization of irinotecan active metabolite (SN38) against physiologic pH through self-assembly of conjugated poly (2-oxazoline) - poly (l-amino acid) block copolymer: A-synthesis and physicochemical characterization

SN-38 is the active metabolite of irinotecan, an FDA-approved chemotherapeutic agent indicated in colorectal carcinoma; however, its clinical applications are still challenging due to low solubility and instability in physiologic condition. Self-assembling block copolymers have attracted great attention to resolve these issues. Therefore, we attempted to synthesize the poly (2-ethyl 2-oxazoline) macro-initiated poly (l-glutamic acid) block copolymers and subsequently to chemically conjugate SN38. The products were characterized by FTIR, 1H NMR and DSC, confirming successful SN38 conjugation via phenyl ester linkage. Pyrene fluorescence assay, DLS and TEM implied formation of self-assembled nanoparticles with sizes about 91 nm at concentrations above 20 μg/ml. Interestingly, the SN38 solubility was enhanced more than 104 folds. Hydrolytic degradation of the SN38 lactone ring was also investigated using a stability-indicating HPLC-UV method, indicating sustained release of the conjugated SN38 attenuated the first-order degradation kinetic compared with free drug. Furthermore, the SN38 conjugated copolymer caused apoptotic death of CT26 cells remarkably more than free drug. Conclusively, the conjugated SN38 is suggested for enhancing the SN38 solubility and stability in physiologic pH.

Effect of vortex‐induced physical stress on fluorescent properties of dye‐containing poly(ethylene glycol)‐block‐poly(lactic acid) micelles

AbstractThe effect of vortex‐induced mechanical stresses on the fluorescent properties of dye‐containing poly(ethylene glycol)‐block‐poly(lactic acid) (PEG‐b‐PLA) block copolymer micelles has been investigated. PEG‐b‐PLA block copolymer micelles containing fluorescent dyes, 3,3′‐dioctadecyloxacarbocyanine perchlorate (DiO) and/or 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI), are prepared by a simple one‐step procedure that involves the self‐assembly of block copolymers and spontaneous incorporation of hydrophobic dyes into the core of the micelles. Upon vortexing, the micelle dispersion samples showed a decrease in fluorescence intensity in a rotational speed‐ and time‐dependent manner. The results demonstrated that the vortexing can alter the fluorescent properties of the dye‐containing PEG‐b‐PLA block copolymer micelle dispersion samples, suggesting the potential utility of block copolymer micelles as a mechanical stress‐responsive nanomaterial.

Sequential Self-Assembly Using Tannic Acid and Phenylboronic Acid-Modified Copolymers for Potential Protein Delivery.

Tannic acid (TA) can form stable complexes with proteins, attracting significant attention as protein delivery systems. However, its systemic application has been limited due to nonspecific interaction. Here, we report a simple technique to prepare systemically applicable protein delivery systems using sequential self-assembly of a protein, TA, and phenylboronic acid-conjugated PEG-poly(amino acid) block copolymers in aqueous solution. Mixing the protein and TA in aqueous solution led to covering of the protein with TA, and subsequent addition of the copolymer resulted in the formation of boronate esters between TA and copolymers, constructing the core-shell-type ternary complex. The ternary complex covered with PEG exhibited a small hydrodynamic diameter of ∼10-20 nm and prevented an unfavorable interaction with serum components, thereby accomplishing significantly prolonged blood circulation and enhanced tumor accumulation in a subcutaneous tumor model. The technique utilizing supramolecular self-assembly may serve as a novel approach for designing protein delivery systems.

Size-dependent soft epitaxial crystallization in the formation of blend nanofiber shish kebabs

Hierarchical structures called nanofiber shish-kebabs (NFSKs) have been studied as a means to decorate or functionalize electrospun nanofibers. Blending natural and synthetic polymers together into the electrospun fiber NFSK backbones offers the opportunity to design materials with finely tuned mechanical and biological properties. However, it is not known how homopolymer and copolymer kebab formation will be impacted by these blend compositions. NFSKs made from polycaprolactone (PCL) and gelatin blend fibers with PCL homopolymer and PCL-block-poly (acrylic acid) (PCL-b-PAA) block copolymer crystalline kebabs were successfully formed. The blend fibers templated crystal growth on the surface, but with a highly irregular kebab orientation and periodicity that was attributed to the large fiber diameter for the blend. Acetic acid was then incorporated into the fibers and shown to improve the phase mixing between PCL and gelatin, leading to smaller diameter electrospun fibers and more regular and periodic kebab NFSK morphology. The study further confirmed the size-dependent soft-epitaxy mechanism in the formation of crystalline shish kebab structures, with the electrospun nanofiber diameter leading to more oriented PCL chains within the fiber and subsequent orientation of the crystallizing kebab polymer. These NFSKs with multicomponent shish and kebabs have potential to be versatile scaffolds for biomineralization and cellular engineering purposes.

Comprehensive study of the formation of stable colloids of Cu[sbnd]Al layered double hydroxide assisted by double hydrophilic block copolymers

The formation of stable aqueous colloidal suspensions of CuAl layered double hydroxide (LDH) assisted by double-hydrophilic block copolymers was investigated. It was of utmost importance since the direct preparation LDH colloids of controlled size is still a major challenge; moreover, regarding the CuAl system, the mechanism of formation of the LDH phase is not well understood yet. CuAl LDH nanoparticles were obtained by complexing Cu2+ and Al3+ cation mixture (Cu2+/Al3+ = 2) with an asymmetric poly(acrylamide)-b-poly(acrylic acid) block copolymer, followed by metal cation hydroxylation. The mechanism of formation of the CuAl LDH was studied and compared to that of MgAl LDH. ICP-MS analysis of the hybrid polyion complex (HPIC) micelles obtained at increasing complexation ratio, i. e. the ratio of the molar concentration of complexing acrylate group of DHBC to M2+ and Al3+ cations (R = AA/(M2+ + Al3+)), showed higher selectivity of DHBC toward Al3+ and, among M2+ cations, for Cu2+ than for Mg2+. Hydroxylation of the HPIC micelles led to macroscopic precipitates at R values below flocculation thresholds, i. e. R1 = 0.43 for DHBC/Cu-Al and 0.13 for DHBC/Mg-Al suspensions, while stable suspensions were formed above R1. The hydrodynamic diameter (Dh) of the colloids determined by DLS decreased from 160 to 50 nm and from 350 to 50 nm in the DHBC/Cu-Al and DHBC/Mg-Al colloids, respectively, when R increased from R1 to 1. XRD and TEM analyses of the dried colloidal suspensions (R > R1) revealed the presence of CuAl LDH and MgAl LDH phases and elemental analyses confirmed that M(II)/Al = 2. Particle sizes were lower in CuAl LDH than in MgAl LDH. Titration curves corresponding to progressive hydroxylation of DHBC/Cu(or Mg)-Al solutions at fixed complexation ratio R allowed establishing that formation of CuAl and MgAl LDH obeyed to a similar sequential mechanism in two steps but involving different aluminum hydroxide precursors according to the different pH values of precipitation. CuAl LDH was obtained by combination of aluminum poly(hydr)oxide species with dissolved copper-based species at pH ~ 5.5, while MgAl LDH resulted from combination of Al(OH)3 and dissolved Mg2+ at pH ~ 8.

Intracellular pH-responsive polymeric micelle for simultaneous chemotherapy and MR imaging of hepatocellular carcinoma

Theranostic nanosystem has been demonstrated great potential in real-timely monitoring drug biodistribution and therapeutic response. It is still a challenge to fabricate a theranostic nanosystem that possesses the properties of good biocompatibility, a high magnetic resonance imaging (MRI) sensitivity, and stimuli-responsive drug release for the diagnosis and treatment of hepatocellular carcinoma. Here, a pH-responsive micelle, which was self-assembled from biodegradable poly(amino acid) block copolymer mPEG-PAsp(DIP)-co-PLLeu, was constructed to load both chemotherapeutic paclitaxel (PTX) and MRI contrast agent superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs/PTX-coloaded PDPL micelle (SPIONs/PTX-PDPL) had a hydrodynamic particle size of 134.5 ± 11.2 nm. The theranostic SPIONs/PTX-PDPL not only effectively delivered PTX and SPION into Bel-7402 cancer cells but also rapidly released PTX in acidic lysosome to induce cell apoptosis. Meanwhile, in vitro MR imaging sensitively detected the liver cancer cells after co-incubation with SPIONs/PTX-PDPL micelle. The SPIONs/PTX-PDPL micelle is a potential theranostic nanosystem in terms of the simultaneous chemotherapy and MR imaging of hepatocellular carcinoma.

Enhancement in proton conductivity by blending poly(polyoxometalate)-b-poly(hexanoic acid) block copolymers with sulfonated polysulfone

Designing polymer chains which contain building blocks with well-defined dimension is an efficient method to induce microphase separation and regulate the ionic channels of polymer electrolyte membranes (PEMs). In this study, a Wells-Dawson-type polyoxometalate (POM) is synthesized and chemically bonded to a norbornene derivative to prepare poly (POM) blocks. Then the block copolymer poly (POM)10-b-poly (COOH)300 is fabricated using poly (POM) and poly (COOH) blocks. Finally, the block copolymer is blended with sulfonated polysulfone (SPS). The electrostatic interactions between the block copolymer and SPS confer the blend membrane with enhanced mechanical and dimensional stabilities. Due to the homogenous distribution of POM clusters and the hydrophilic-hydrophobic interactions between POMs and polymer backbones, the adjacent hydrophilic domains are connected and continuous proton-transfer channels are induced. As a result, the blend membrane displays proton conductivity of 0.053 S cm−1 (25 °C, 100% RH) and 1.5 × 10−2 S cm−1 (80 °C, 40% RH), which are 2.52 and 6.25 times higher than those of the plain SPS membrane. Furthermore, SPS/POM-BC-30 shows a maximum power density of 164.9 mW cm−2, which is 54.7% higher than SPS.