Self-assembling Amphiphilic Block Research Articles

Mimicking effects of cholesterol in lipid bilayer membranes by self-assembled amphiphilic block copolymers.

The effect of cholesterol on biological membranes is important in biochemistry. In this study, a polymer system is used to simulate the consequences of varying cholesterol content in membranes. The system consists of an AB-diblock copolymer, a hydrophilic homopolymer hA, and a hydrophobic rigid homopolymer C, corresponding to phospholipid, water, and cholesterol, respectively. The effect of the C-polymer content on the membrane is studied within the framework of a self-consistent field model. The results show that the liquid-crystal behavior of B and C has a great influence on the chemical potential of cholesterol in bilayer membranes. The effects of the interaction strength between components, characterized by the Flory-Huggins parameters and the Maier-Saupe parameter, were studied. Some consequences of adding a coil headgroup to the C-rod are presented. Results of our model are compared to experimental findings for cholesterol-containing lipid bilayer membranes.

Selinexor-Loaded Polymeric Micelles for Multiple Myeloma Therapy

Introduction Multiple myeloma (MM) is characterized by the clonal proliferation of abnormal plasma cells in the bone marrow. Selinexor (SEL) is an XPO1 inhibitor, and in a pivotal clinical trial, the SEL and dexamethasone regimen showed a 26% of partial response rate or better, with two patients achieving stringent complete response. However, the single-agent efficacy of SEL was modest, with systemic toxicities including thrombocytopenia and gastrointestinal symptoms that negatively impacted the quality of life. Nanomedicine refers to the ingenious design of nanoscale biomaterials for drug delivery. Polymeric micelles are made up of self-assembled amphiphilic block polymers and act as an effective strategy to address the challenge of free drug administration. To reduce side effects and improve therapeutic efficacy, we reported our work on SEL delivery using mPEG-PCL micelles for the treatment of MM. Materials and Methods The SEL-loaded micelles were developed through thin-film hydration. The mean particle size, zeta potential, and polydispersity index of micelles were assessed by a Malvern Nano-ZS 90. The release behavior of the mPEG-PCL-SEL micelle was determined by a dialysis method in vitro. The cytotoxicity and apoptosis rate of the mPEG-PCL-SEL micelle were assessed on the RPMI-8226 cell line and the ARD cell line. The ARD orthotopic MM model was developed by intravenous administration of ARD-luc cells into 6-week-old B-NDG mice. Four groups were treated with saline, blank micelles, or mPEG-PCL-SEL micelles (SEL concentrations: 2.5 and 5 mg/kg) via intravenous injection, and the other four groups were given free-SEL via oral gavage (SEL concentrations: 2.5, 5, 10, and 15 mg/kg), respectively. All of the treatments were given twice a week for two weeks. To evaluate the tumor burden, bioluminescence imaging was monitored. Brain samples were collected for assessment of brain penetration ability of the micellar formulation. In addition, the animal weight, peripheral blood counts, and condition of mice were measured to investigate the side effects. Results The particle size of the mPEG-PCL-SEL micelle was 31.3 nm, the PDI was 0.11-0.16, and the zeta potential was −4.52 mV. The encapsulation efficacy was 90.56%. The micelles remained stable for a long period and exhibited a controlled release behavior. In addition, the mPEG-PCL-SEL micelle exhibited enhanced cellular uptake ability and efficient cytotoxicity toward MM cells. Most importantly, in the orthotopic MM model, this micelle system exhibited impressive therapeutic efficacy. The 5 mg/kg mPEG-PCL-SEL micelle group demonstrated better treatment efficacy than the 10 mg/kg free-SEL group according to the quantitative analysis of tumor bioluminescence, indicating the superior therapeutic activity, although there was no significant difference. Surprisingly, the SEL-loaded micelle efficiently prolonged the survival of myeloma-bearing mice. Besides, the micellar formulation possessed a reduced brain penetration property which may contribute to improved tolerability. And mice in the SEL-micelle groups did not show abnormal situation of hematopoietic cells and weight loss. The micelle demonstrated a favorable safety profile. Discussion and conclusions In this work, we developed mPEG-PCL-SEL micelles with thin-film hydration. To the best of our knowledge, no relevant studies of SEL delivery have been reported. The micelle formulation showed good stability and controlled release manner. Besides, the mPEG-PCL-SEL micelle induced comparable or even better levels of cytotoxicity compared with the free-SEL in vitro. Most importantly, the mPEG-PCL-SEL micelle exhibited improved therapeutic efficacy compared with the free-SEL at the same dose level and showed similar or better therapeutic outcomes than the high-dose free-SEL, performed with survival benefit. Meanwhile, the micelle formulation possessed acceptable tolerability and safety profile. It is worth noting that none of the treatment groups achieved complete remission. This may be due to the limited treatment efficacy of a single agent. Hence, nanomedicine-based combination therapy containing SEL can be studied to further improve the efficacy of MM treatment.

Recent Advancement of Polymersomes as Drug Delivery Carrier.

Biomedical applications of polymersomes have been explored, including drug and gene delivery, insulin delivery, hemoglobin delivery, the delivery of anticancer agents, and various diagnostic purposes. Polymersomes, which are self-assembled amphiphilic block copolymers, have received a lot of attention in drug delivery approaches. This review represents the methods of preparation of polymersomes, including thin-film rehydration, electroformation, double emulsion, gel-assisted rehydration, PAPYRUS method, and solvent injection methods, including various therapeutic applications of polymersomes. Data was searched from PubMed, Google Scholar, and Science Direct through searching of the following keywords: Polymersomes, methods of preparation, amphiphilic block copolymers, anticancer drug delivery. Polymersomes provide both hydrophilic and hydrophobic drug delivery to a targeted site, increasing the formulation's stability and reducing the cytotoxic side effects of drugs. Polymersomes have the potential to be used in a variety of biological applications, including drug and gene delivery, insulin delivery, hemoglobin delivery, delivery of anticancer agents, as well as in various diagnostic purposes. Recently, polymersomes have been used more frequently because of their stability, reducing the encapsulated drug's leakage, site-specific drug delivery, and increasing the bioavailability of the drugs and different diagnostic purposes. The liposomes encapsulate only hydrophilic drugs, but polymersomes encapsulate both hydrophilic and hydrophobic drugs in their cores.

Sunlight-induced photo-thermochromic smart window based spiropyran-functionalized copolymer for UV shielding and sunlight management

Energy efficient smart windows that automatically regulate the transmission of solar energy are one of the most promising ways to reduce energy consumption in buildings. However, current thermochromic smart windows based on Poly (N-isopropylacrylamide) (PNIPAm) only focus on the modulation of solar light through the phase transition of the material, while the contribution in UV modulation and energy storage are weak. Herein, we report a liquid thermo-responsive smart window Poly (NIPAm-co-SPMA7%) with UV resistance, light modulation and energy storage constructed by self-assembled amphiphilic block copolymer nanoparticles dispersed in water. Poly (NIPAm-co-SPMA7%) smart window has excellent thermal response solar modulation (Tlum, 20°C = 90.07% and ΔTsol = 87.59%), excellent energy absorption and storage capacity in aqueous solution, and strong absorption of UV light. In addition, this liquid smart window has a simple structure, good uniformity and scalability, which opens up a new way for energy-saving smart windows.

Molecular dynamics simulation based design of biomimetic membrane with artificial water channels

Inspired by nature’s design of pore proteins embedded in cell membranes, synthetic pore molecules embedded in self-assembled amphiphilic block copolymer membranes are the subject of intensive current research, as a possible route to more efficient reverse osmosis (RO) membranes. RO membranes are the key element in producing drinkable water from brackish or sea water; improved materials would help make this expensive process more widely applicable, increasing fresh water supplies worldwide. In this work, we simulated polybutadiene–polyethylene oxide (PB–PEO) bilayers containing peptide-appended pillar[5]arene (PAP5) channels. PB–PEO bilayers with PAP5 channels are a biomimetic alternative to aquaporin embedded lipid membranes, with high water permeability combined with excellent selectivity. In our simulations, we systematically varied the PB–PEO block copolymer structure to maximize water mobility. We measured water diffusivity in our best design by two complementary methods, and compared our values to that inferred from experimental channel permeability. In this design, we obtained a water diffusivity of 30.38 ± 0.19 × 10−8cm2s−1, comparable to the best experimentally reported result. We find that the highest permeability is achieved when the bilayer hydrophobic thickness matches the PAP[5] dimension, and the hydrophilic block is long enough that clogging the pore is entropically unlikely.

Characterizing the Core-Shell Architecture of Block Copolymer Nanoparticles with Electron Microscopy: A Multi-Technique Approach.

Electron microscopy has proved to be a major tool to study the structure of self-assembled amphiphilic block copolymer particles. These specimens, like supramolecular biological structures, are problematic for electron microscopy because of their poor capacity to scatter electrons and their susceptibility to radiation damage and dehydration. Sub-50 nm core-shell spherical particles made up of poly(hydroxyethyl acrylate)–b–poly(styrene) are prepared via polymerization-induced self-assembly (PISA). For their morphological characterization, we discuss the advantages, limitations, and artefacts of TEM with or without staining, cryo-TEM, and SEM. A number of technical points are addressed such as precisely shaping of particle boundaries, resolving the particle shell, differentiating particle core and shell, and the effect of sample drying and staining. TEM without staining and cryo-TEM largely evaluate the core diameter. Negative staining TEM is more efficient than positive staining TEM to preserve native structure and to visualize the entire particle volume. However, no technique allows for a satisfactory imaging of both core and shell regions. The presence of long protruding chains is manifested by patched structure in cryo-TEM and a significant edge effect in SEM. This manuscript provides a basis for polymer chemists to develop their own specimen preparations and to tackle the interpretation of challenging systems.

Biomolecules Turn Self-Assembling Amphiphilic Block Co-polymer Platforms Into Biomimetic Interfaces.

Biological membranes constitute an interface between cells and their surroundings and form distinct compartments within the cell. They also host a variety of biomolecules that carry out vital functions including selective transport, signal transduction and cell-cell communication. Due to the vast complexity and versatility of the different membranes, there is a critical need for simplified and specific model membrane platforms to explore the behaviors of individual biomolecules while preserving their intrinsic function. Information obtained from model membrane platforms should make invaluable contributions to current and emerging technologies in biotechnology, nanotechnology and medicine. Amphiphilic block co-polymers are ideal building blocks to create model membrane platforms with enhanced stability and robustness. They form various supramolecular assemblies, ranging from three-dimensional structures (e.g., micelles, nanoparticles, or vesicles) in aqueous solution to planar polymer membranes on solid supports (e.g., polymer cushioned/tethered membranes,) and membrane-like polymer brushes. Furthermore, polymer micelles and polymersomes can also be immobilized on solid supports to take advantage of a wide range of surface sensitive analytical tools. In this review article, we focus on self-assembled amphiphilic block copolymer platforms that are hosting biomolecules. We present different strategies for harnessing polymer platforms with biomolecules either by integrating proteins or peptides into assemblies or by attaching proteins or DNA to their surface. We will discuss how to obtain synthetic structures on solid supports and their characterization using different surface sensitive analytical tools. Finally, we highlight present and future perspectives of polymer micelles and polymersomes for biomedical applications and those of solid-supported polymer membranes for biosensing.

Effect of the Micelle Opening in Self-assembled Amphiphilic Block Co-polymer Films on the Infiltration of Inorganic Precursors.

Infiltration of the polymer templates with inorganic precursors using the selective vapor-phase infiltration approach, or sequential infiltration synthesis (SIS), allows the design of materials with advanced properties. Swelling of the block co-polymer (BCP) templates enables the additional control of the structure, porosity, and thickness of the composite or inorganic materials. Here, we use the highly precise quartz crystal microbalance (QCM) technique to investigate quantitatively the effect of the micelle opening by swelling and inorganic precursor infiltrating on the evolution of porosity in amphiphilic BCPs. We show that swelling of the polystyrene- block-poly-4-vinyl pyridine (PS- b-P4VP) BCP in ethanol at 75 °C occurs rapidly and results in a stable polymer structure in 30 min. By using an alumina model system, we found that swelling enables access to all available polar domains of the PS- b-P4VP film leading to an increase in the SIS-infiltrated alumina mass as compared to the nonswelled BCP layer. Our results demonstrate that swelling of the 110 nm thick BCP template results in the formation of 192 nm thick alumina films with 2 times larger alumina mass and 4 times larger effective pore volume than in case of the nonswelled sample. In the case of the thicker polymer template, the difference due to swelling becomes even more substantial because the fraction of accessible polymer is increased much more than in thin films. Our findings provide important insights into the mechanism of the infiltration of the inorganic precursors into swelled and nonswelled, spin-coated BCP templates enabling the design of highly porousthick ceramic films by SIS.

Block copolymers for designing nanostructured porous coatings.

Highly ordered porous coatings find applications in many fields, such as nanotechnology, microfluidics and nanofluidics, membrane separation, and sensing. In recent years, there has been great interest regarding the synthesis of isoporous and well-ordered (in)organic coatings for the production of highly selective functional membranes. Among the different strategies that have been proposed to date for preparing these porous thin coatings, one simple route involves the use of self-assembled amphiphilic block copolymers either as the porogen (acting as sacrificial templating agents for the production of inorganic architectures) or as a source of the porogen (by self-assembly for the production of polymeric substrates). Therefore, an extended discussion around the exploitation of block copolymers is proposed here in this review, using polystyrene-block-polyethylene oxide (PS-b-PEO) as the model substrate, and critical points are highlighted.

Interactions between citrate-capped gold nanoparticles and polymersomes

Polymersomes are vesicles formed by self-assembled amphiphilic block copolymers. Polymersomes generally have better stability than liposomes and they have been widely used in making drug delivery vehicles. In this work, the interaction between two types of polymersomes and citrate-capped gold nanoparticles (AuNPs) was studied. The following two polymers: poly(2-methyloxazoline-b-dimethylsiloxane-b-2-methyloxazoline) (called P1) and poly(butadiene-b-ethylene oxide) (called P2) were respectively used to form polymersomes. While P1 only formed spherical vesicle structures, worm-like structures were also observed with P2 as indicated by cryo-TEM. Both polymersomes adsorbed AuNPs leading to their subsequent aggregation. A lower polymersome concentration produced more obvious aggregation of AuNPs as judged from the color change. Capping AuNPs with glutathione inhibited adsorption of AuNPs. Considering the surface property of the polymers, the interaction with AuNPs was likely due to van der Waals forces. P1 polymersomes encapsulated calcein stably and AuNPs did not induce leakage. The P1/AuNP complex was more efficiently internalized by HeLa cells compared to free P1 polymersomes, further indicating a stable adsorption under cell culture conditions. In summary, this work indicates citrate-capped AuNPs form stable adsorption complexes with these polymersomes and their interactions have been explored.

Combined mathematical modelling and experimentation to predict polymersome uptake by oral cancer cells

This study is motivated by understanding and controlling the key physical properties underlying internalisation of nano drug delivery. We consider the internalisation of specific nanometre size delivery vehicles, comprised of self-assembling amphiphilic block copolymers, called polymersomes that have the potential to specifically deliver anticancer therapeutics to tumour cells. The possible benefits of targeted polymersome drug delivery include reduced off-target toxic effects in healthy tissue and increased drug uptake by diseased tissue. Through a combination of in vitro experimentation and mathematical modelling, we develop a validated model of nanoparticle uptake by cells via the clathrin-mediated endocytotic pathway, incorporating receptor binding, clustering and recycling. The model predicts how the characteristics of receptor targeting, and the size and concentration of polymersomes alter uptake by tumour cells. The number of receptors per cell was identified as being the dominant mechanism accounting for the difference between cell types in polymersome uptake rate. From the Clinical EditorThis article reports on a validated model developed through a combination of in vitro experimentation and mathematical modeling of nanoparticle uptake by cells via the clathrin-mediated endocytotic pathway. The model incorporates receptor binding, clustering, and recycling and predicts how the characteristics of receptor targeting, the size and concentration alter polymersome uptake by cancer cells.

Viscoelastic Properties of Water Suspensions of Polymer Nanofibers Synthesized via RAFT-Mediated Emulsion Polymerization

We report on the rheological properties of water suspensions of poly(methacrylic acid-co-poly(ethylene oxide) methyl ether methacrylate)-b-polystyrene and poly(methacrylic acid-co-poly(ethylene oxide) methyl ether methacrylate)-b-poly(methyl methacrylate) self-assembled amphiphilic block copolymer nanofibers, synthesized via RAFT-mediated aqueous emulsion polymerization. The viscoelastic properties were studied over a range of nanofiber concentrations spanning the transition from the dilute to semidilute regimes. From the measured viscoelastic parameters, two sets of suspensions could be differentiated depending on their aspect ratio (length/diameter ≈70 and ≈54) and the average length of the nanofibers was calculated in the 2.4 μm – 3.8 μm range. The viscoelastic properties appeared to depend mainly on the aspect ratio of the fibers rather than on their nature and composition. As expected the zero shear viscosity was observed to scale with the volume fraction ϕ as η0 ∝ ϕ1 and η0 ∝ ϕ3 for dilute and semid...

Direct Molar Mass Determination of Self-Assembled Amphiphilic Block Copolymer Nanoobjects Using Electrospray-Charge Detection Mass Spectrometry

Charge detection mass spectrometry (CD-MS) combined with electrospray ionization was used to determine, in a direct way and for the first time, the molar mass of self-assembled amphiphilic block copolymer nanoobjects prepared via living radical emulsion polymerization. CD-MS supplies enough data for calculating statistically significant measurements of the mass of particles in the megadalton to gigadalton range and their resulting mass distribution.

Self-assembled nanomicelles using PLGA–PEG amphiphilic block copolymer for insulin delivery: a physicochemical investigation and determination of CMC values

Self-assembled nanomicelles can be used as synthetic biomaterials and colloidal carriers for poorly water-soluble drug delivery systems. Some of these micellar systems have been introduced in clinical trials and showed hopeful results relating to their therapeutic index in patients. Biodegradable nanomicelle was prepared from self-assembling amphiphilic block copolymer composed of poly(DL-lactic-co-glycolic acid) (PLGA) as a core and polyethylene glycol (PEG) as a corona. The PLGA-PEG block copolymer was first synthesized and characterized by FTIR, (1)H NMR, GPC and inherent viscosity measurements. The nanomicelle formed by PLGA-PEG block copolymer in the aqueous solution was characterized by dynamic light scattering, zeta potential, scanning electron microscopy (SEM) and fluorescence excitation and emission spectra of pyrene probe. The critical micelle concentration of obtained nanomicelle was about 0.006 mg/mL, with the size of about 160 nm and the zeta potential of -29 mV. Insulin-loaded PLGA-PEG nanomicelles were prepared by modified dialysis method and the physicochemical parameters of the micelles such as drug content, entrapment efficiency and in vitro drug release were characterized. The results showed that insulin was entrapped into PLGA-PEG nanomicelles with drug loading of 3.9 wt% and entrapment efficiency of 55 wt%. The nanomicelles containing insulin exhibited a controlled release profile. These observations suggested that the PLGA-PEG block copolymers nanomicelles have been prepared by a new synthetic route are potent nanocarrier for poorly water-soluble drugs as insulin.

Abstract 369: Redox nanoparticle for tumor imaging and anticancer drug enhancer

Abstract Recently, a non-invasive in vivo imaging of low pH circumstances has attracted attention as new means of detecting disease and response to clinical treatment. Low pH circumstances, which are an aberration of normal pH homeostasis, are caused by ischemia, infection or inflammation, extracellular acidosis in tumors, wound healing, and so forth. However, there is currently no clinical tool available to capture an image of low pH circumstances in vivo. We have been focusing on preparation of core-shell type nanoparticles by self-assembling of amphiphilic block copolymers. Especially, we have succeeded to prepare pH-sensitive nanoparticles, which disintegrate under acidic environment. Thus, using these nanoparticles, ON-OFF regulation of signals in responce to the acidic environment could be monitored. Since nitroxyl radical is susceptible to both electron spin and nuclear magnetic resonances (ESR and NMR), it is anticipated to utilize as imaging compound. Under in vivo conditions, however, low-molecular-weight nitroxyl radicals pose several problems, such as nonspecific accumulation in normal tissues, preferential renal clearance, and rapid reduction of the nitroxyl radical. To solve these difficulties, we have confined nitroxyl radicals in the core of pH-sensitive nanoparticle (RNP) using a self-assembling amphiphilic block copolymer composed of a hydrophilic poly(ethylene glycol) segment and a hydrophobic polystyrene segment carrying nitroxyl radical in each repeating unit as side chain. The cumulant average diameter of the RNP under neutral pH was about 40 nm, and the RNP collapses under the acidic conditions. At the same time, the RNP emitted an intense ESR and NMR signals. Due to the confinement of nitroxyl radical in the core of the RNP, the blood circulation was extended. The nitroxyl radicals in the nanoparticles showed reduction resistance even in the presence of ascorbic acid. In vitro and in vivo toxicity were also reduced significantly. Thus, we can utilize it as a bioimaging probe, which observe acid environment in vivo. An excessive reactive oxygen species (ROS) causes severe side effects in versatile diseases. For example, ischemia-reperfusion injury is one of the most famous damages by ROS, which are produced after a long ischemic period. Therefore, the protection of organs affected by ROS must be considered in order to minimize the area of damage associated with ischemia-reperfusion. Since nitroxyl radical can react catalytically with ROS, RNP was anticipated to scavenge ROS after reperfusion. The RNP was confirmed to show protective effect to several types of ischemia-reperfusion injuries such as brain, heart and kidney. It is also interested to note that RNP improved efficiency of anticancer drug doxorubicin (DOX) when RNP is administered before DOX administration. Thus, RNP is promising as new nanomedicine for clinical applications for versatile therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 369. doi:10.1158/1538-7445.AM2011-369

Nitroxyl Radical-Containing Nanoparticles for Novel Nanomedicine Against Oxidative Stress Injury

This article discusses the preparation and characterization of pH-sensitive nitroxyl radical-containing nanoparticles (RNPs) possessing nitroxyl radicals in the core and reactive groups on the periphery, and its biomedical application. The RNPs prepared by a self-assembling amphiphilic block copolymers composed of a hydrophilic poly(ethylene glycol) (PEG) segment and a hydrophobic poly(chloromethylstyrene) (PCMS) segment in which the chloromethyl groups were converted to 2,2,6,6-tetramethylpiperidinyloxyls (TEMPOs) via an amination of PEG-b-PCMS block copolymer with 4-amino-TEMPO are initially described. The cumulant average diameter of an RNP is approximately 40 nm, and the RNP has intense electron paramagnetic resonance signals. RNPs show a prolonged blood circulation time by the compartmentalization of nitroxyl radicals into the hydrophobic core, and disintegrate in response to a low pH environment, such as ischemic tissue, resulting in effectively scavenging reactive oxygen species due to an exposure of nitroxyl radicals from the RNP core. Thus, the RNP prepared was found to be effective for cerebral ischemia-reperfusion injury. Therefore, RNPs are promising as high-performance therapeutic nanomedicine for oxidative stress injuries.

Establishing Conditions for Compartmentalized and Lamellar Biomimetic Supported Biomimetic Membranes

Lipid bilayers have typically been used as model systems of biological membranes to investigate for example protein reconstitution, endo and exocytosis, organelle fusion and membrane permeation induced by channel-forming proteins and toxins. However, lipid membranes suffer from low stability and technical application requires stabilization for example by crosslinking, deposition on a support or encapsulation with hydrogel. Recently, self-assembling amphiphilic block copolymers have shown promise as biomimetic membranes due to their stability, which makes it possible to work in a broader range of temperature, pH, pressure and time. However, polymers generally form films with higher hydrophobic thickness than lipid bilayers. Also, lipid membranes are able to form planar bilayers on a support surface by vesicle fusion with the surface, whereas block copolymers cannot. Here we combine lipids and block copolymers and investigate stability and deposition on a support surface. We have mixed PMOXA-PDMS-PMOXA triblock copolymer with zwitterionic or positively charged lipids. We have investigated mixed polymer/lipid vesicles by transmission electron microscopy, quartz crystal microbalance with dissipation monitoring, dynamic light scattering, stopped-flow measurements and atomic force microscopy. We show that mixing the triblock copolymer with lipids allowed us to form mixed polymer-lipid vesicles rather than segregated lipid vesicles and polymer vesicles. These vesicles had the stability of polymer vesicles, but were able to adhere well to quartz and mica surfaces like lipid vesicles. We demonstrated that planar supported membranes or tethered compartmentalized membranes could be formed on mica and quartz and showed that the transition depends on the lipid to polymer molar ratio. We concluded that mixed polymer/lipid membranes present an attractive environment for transmembrane proteins, because the addition of only 20 mol% polymer lead to vesicles with polymer-like stability and low water permeability while still providing a sufficiently lipidic protein environment.

Bionic soft crystalline lens materials for MEMs applications based on self-assembling amphiphilic block copolymer/nanoparticle hybrids

In this study, a biomimetic crystalline lens with properties that combine the softness of a hydrogel comparable to that of a human lens for adjustable focus and the property for image aberration correction with gradient refractive index (GRIN) was developed by the self-organization of an amphiphilic block copolymer blended with high refractive index titanium nanoparticles (TiO2). The hydrogel lens was prepared by using a thermally responsive poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PPO–PEO–PPO) triblock copolymer (Poloxamer 407) with the lower-critical solution temperature (LCST) property that can be injectable into the eye capsule as a liquid below its LCST and solidifies as a soft gel above the LCST at the human body temperature. By chemical modification of the triblock copolymer with double bonds on its chain-ends (Poloxamer 407A), the soft lens network can be made by using UV crosslinking of the hydrogel. To further increase the refractive index (RI) of the hydrogel lens network and to match its RI to that of the human lens (=1.41), highly visible-light transparent titanium dioxide (TiO2) nanoparticles were introduced into the hydrogel lens network. To create a biomimetic GRIN lens as in the human’s eyes, an electric field method was also used to induce an axial diffusion of TiO2 nanoparticles from the center of the lens where TiO2 nanoparticles were first injected to the edge. The above method demonstrates the potential to use the hydrogel/nanoparticle hybrid as an injectable replacement for a soft optical lens system with an adjustable focus for future MEMs application.

Self-Assembled Amphiphilic Block Copolymers

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.

PH-Sensitive Radical-Containing-Nanoparticle (RNP) for the L-Band-EPR Imaging of Low pH Circumstances

For the imaging of low pH circumstances in vivo, a pH-sensitive radical-containing-nanoparticle (RNP), which has an intense electron paramagnetic resonance (EPR) signal, was designed and developed using a self-assembling amphiphilic block copolymer (PEG-b-PCTEMPO) composed of a hydrophilic poly(ethylene glycol) (PEG) segment and a hydrophobic poly(chloromethylstyrene) (PCMS) segment in which the chloromethyl groups were converted to 2,2,6,6-tetramethylpiperidinyloxys (TEMPOs) via the amination of PEG-b-PCMS block copolymer with 4-amino-TEMPO. This RNP formed core-shell-type micelles in the physiological environment, and the cumulant average diameter of the RNP was about 50 nm. The cytotoxicity and acute toxicity studies for the RNP revealed that the median inhibitory concentration (IC(50)) of TEMPO radicals in RNP core and median lethal dose (LD(50)) of RNP were >8 mmol N(TEMPO)/L and >600 mg/kg (>960 mumol N(TEMPO)/kg), respectively, indicating fairly low toxicity. The blood circulation of the RNP was evaluated using ICR mice. Contrary to the rapid clearance of low-molecular-weight TEMPO derivatives such as 4-hydroxy-TEMPO (TEMPOL) from the bloodstream, the EPR signal of the RNP remained for a fairly long period of time. Actually, the signal was observed in the blood for more than 2 h, as monitored by EPR spectroscopy. The compartmentalization of the TEMPO radicals in the RNP core improved the stability in the bloodstream. Since an amino group was introduced in each repeating unit of the PCTEMPO segment, the disintegration of the RNP was caused by the protonation of the amino groups in response to the acidic pH environment (pH < 6.0), as confirmed by the dynamic light scattering (DLS) measurements. In addition, a drastic change in the EPR spectra from broad to sharp triplet was observed, accompanying the disintegration. This change was based upon the mobility of the TEMPO moieties covalently conjugated in the hydrophobic segment, which was confirmed by the rotational correlation time of the TEMPO moieties on the PCTEMPO segment. Note that the peak intensity of the EPR signal increased at around the phase transition point (ca. pH = 6.0). When pH-sensitive RNP solutions at pH values 5.6 and 7.4 were visualized using an L-band EPR imaging system, the phantom images showed a remarkable on-off regulation in response to the acidic pH environment. These results demonstrate that pH-sensitive RNPs are expected to serve as nanoprobes for the in vivo EPR imaging of low pH circumstances.