Hybrid Micelles Research Articles

Preparation, properties and formation mechanism of zirconium-Si hybrid high transmittance hydrophobic coating

A two-step synthesis method of a new hybrid coating was discussed. Zirconium silicate hybrid sol was prepared by in-situ hydrolysis polymerization of zirconium acetate (ZrAc) and Octyltrimethoxy silane (OTMS) in alcohol water system. FTIR characterization showed that ZrAc was hydrolyzed and polymerized in situ to form zirconium sol. Octyl trimethoxysilane (OTMS) was hydrolyzed and grafted onto zirconium sol to form octyl coated silicon zirconium hybrid micelles. The co-hydrolysis time of OTMS and ZrAc sol is an important factor affecting the octyl content in ZrAc-OTMS micelles, which affects the hydrophobicity, hardness and light transmittance of the coating. Once appropriately prolonging the co-hydrolysis time, the octyl content in ZrAc-OTMS micelles, hydrophobic angle and light transmittance of the composite coating will increase while the hardness will decrease. Too long co-hydrolysis time will lead to the opposite results. When the co-hydrolysis time is 50 min, the film is drawn on the common glass substrate by one step immersion method. The hydrophobic angle of the coating reaches 132.01°at room temperature. The hardness of pencil is higher than 3 H. The bonding force is Grade 0. The visible light transmittance is 95.30%, and the visible light transmittance of glass matrix is increased by 2.54%. XPS and SEM analysis results showed that the ZrAc-OTMS hybrid coating has a lamellar, micro porous structure with a diameter about 60–200 nm, and low surface energy modified by octyl hydrophobic groups on the micelles, which plays a lotus leaf effect and improves the hydrophobicity of the coating.

PEGylated phospholipid micelles containing D-α-tocopheryl succinate as multifunctional nanocarriers for enhancing the antitumor efficacy of doxorubicin

The aim of this investigation is to clarify the effect of D-α-tocopheryl succinate (vitamin E succinate, VES) and distearoylphosphatidyl ethanolamine-poly(ethylene glycol) (DSPE-PEG) on the encapsulation and controlled release of doxorubicin (DOX) in nano-assemblies and their consequences on the anti-tumor efficacy of DOX. DOX molecules were successfully loaded into the hybrid micelles with VES and DSPE-PEG (VDPM) via thin-film hydration method, exhibiting a small hydrodynamic particle size (~30 nm) and a weak negative zeta potential of around −5 mv. The obtained DOX-loaded VDPM2 displayed retarded DOX release at pH of 7.4, while substantially accelerated drug release at acidic pH of 5.0. Furthermore, the DOX-loaded VDPM2 exhibited substantially slower drug release rate at pH 7.4 compared with the drug-loaded VDPM1 or DPM preparation, benefiting for decreasing the premature DOX release during blood circulation. In vitro cell experiment indicated that DOX-loaded micelles (DPM, VDPM1 and VDPM2) improved the cellular uptake of DOX in 4T1 and MDA-MB-231 cells. The existence of VES component in the structure of DOX-loaded micelles had no obvious influence on the subcellular distribution of the encapsulated DOX molecules. Furthermore, the DOX-loaded VDPM2 exhibited more pronounced cytotoxicity to 4T1 and MDA-MB-231 cancerous cells compared with DOX-loaded DPM and free DOX solution. The hybrid nanocarriers including VES and DSPE-PEG selectively induced intracellular ROS accumulation and increased level of cytoplasmic calcium ion in cancerous cells by interacting with mitochondria and endoplasmic reticulum, bringing about the improved cytotoxicity of DOX. In vivo antitumor efficacy investigation of DOX-loaded VDPM2 against 4T1 xenograft-bearing mice displayed satisfied therapeutic activity with negligible systemic toxicity, as evidenced by the histological analysis and change of body weight. The proposed DOX-loaded VDPM preparation, as a mulifunctional chemotherapeutic nanomedicine system, holds great potential and bright prospect for clinical tumor therapy.

Metallic Oxide-Induced Self-Assembly of Block Copolymers to Form Polymeric Hybrid Micelles with Tunable Stability for Tumor Microenvironment-Responsive Drug Delivery.

Since block copolymers are able to self-assemble into various polymeric architectures, it is intriguing to explore a unique self-assembly strategy for polymers. Two different metallic oxides [manganese dioxide (MnO2) and zinc oxide (ZnO)] are displayed herein to demonstrate this self-assembly mechanism of polymers. In situ generation of metallic oxides induces self-assembly of block copolymers to form polymeric hybrid micelles with tunable stability in aqueous solutions. These final ZnO-cross-linked polymeric micelles exhibited a high drug loading capacity of 0.41 mg mg-1 toward doxorubicin (DOX), whereas DOX-loaded ZnO-cross-linked polymeric micelles could be broken down into Zn2+ and polymer scraps, which facilitated drug release in tumor microenvironments. Both in vitro and in vivo investigations showed that the drug-loaded ZnO-cross-linked polymeric micelles effectively suppressed tumor growth. Accordingly, the present study demonstrates a novel strategy of polymer self-assembly for fabricating polymeric architectures that can potentially provide insight for developing other polymeric architectures.

Studying the suitability of hybrid micelle liquid chromatography for estimating the lipophilicity of some partial dopamine agonists used to attain the reward circuit.

Three micellar-based mobile phases were developed and optimized for the simultaneous determination of certain partial dopamine agonists that are used to overcome the withdrawal symptoms of abused drugs, namely aripiprazole, pramipexole and piribedil. The studied drugs were separated using micellar liquid chromatography, hybrid micellar liquid chromatography (HMLC) and microemulsion liquid chromatography (MELC). The three developed mobile phases were studied to estimate their suitability for the measurement of log p-values of the studied drugs. Experimental determination of log Pm/w values using the three mobile phases demonstrates that HMLC is the mobile phase of choice since the obtained practical log Pm/w values were in accordance with the reported log P values, and calculated log P and log D values. An explanation of the obtained results was presented based on the separation retention mechanism for each chromatographic technique. Furthermore, the effect of the pH and the column temperature in HMLC on the practical log Pm/w values was studied. To verify its suitability for experimental measurement of log Pm/w , HMLC was subjected to full validation according to the United States Pharmacopeia.

Hybrid micelles codelivering shikonin and IDO-1 siRNA enhance immunotherapy by remodeling immunosuppressive tumor microenvironment

Cancer immunotherapy is becoming an important option for malignant tumors treatment. Unfortunately, lacking intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and immunosuppressive tumor microenvironment (ITM) remian primary barriers that immensely hamper its further clinical application. For boosting immune response and rebuilding the ITM, valid hybrid micelles (SK/siIDO1-HMs) delivering shikonin (SK) and IDO-1 knockdown siRNA (siIDO1) were conducted. SK/siIDO1-HMs had sufficient circulation time, favorable intratumoral accumulation and rapidly release in the cytoplasm. Importantly, SK was demonstrated to significantly elicit intratumoral accumulation of CTLs through inducing immunogenic cell death (ICD) of tumor cells. Moreover, siIDO1 downregulated the IDO-1-caused immunosuppression and restrained regulatory T lymphocytes (Tregs). In summary, SK/siIDO1-HMs displayed a remarkable potential for tumor therapy via triggering the ICD and moderating the IDO-1-triggered immunosuppression.

Hybrid micelles enhance tumour therapy by remodelling biodistribution and improving intracellular drug release.

PEGylated micelles have been widely used for tumour therapy. Although PEGylation can prolong the blood circulation time, there is only less than 5% of administered micelles that can be transported to tumour sites and over 95% are cleared by the reticuloendothelial system (RES). Besides, the limited intracellular drug release also restricts their efficacy. To improve the therapeutic efficacy of PEGylated micelles, a safe, simple and efficient hybrid micellar system, composed of poly(aminoethyl ethylene phosphate)-poly(L-lactic acid) (PAEEP-PLLA) and poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLLA), was developed. The hybrid micelles significantly prolonged the blood circulation time by decreasing the plasma protein adsorption and reducing the clearance by the RES. The deposition of the hybrid micelles in the liver and spleen was reduced, and the tumour accumulation was greatly improved. In addition, the intracellular drug release of the hybrid micelles was obviously increased due to the easy degradation of PAEEP in the endo/lysosomes. The tumour growth inhibition efficiency of the hybrid micelles was much higher than that of the PEG-PLLA micelles (84.5% vs. 44.5%). Furthermore, the hybrid micelles exhibited low hemolysis and reduced deposition in normal organs, which revealed their excellent bio-safety. Therefore, we established a promising hybrid micelle system for efficient anti-tumour therapy.

Estimating chiral selector potential of micelle-based mobile phases through the analysis of some enantiomeric mixtures

The present work aims to present two new concepts concerned with chiral separation. First, chiral separation of some enantiomeric drugs, using micelle-based liquid chromatography without any chiral selector, whether in the stationary phase or the mobile phase, was performed. The surfactants used were anionic; sodium dodecyl sulphate, and cationic; cetrimide. The studied analytes include phenyl-ephrine hydrochloride (PHR), cetirizine dihydrochloride (CTZ), and mebeverine hydrochloride (MBV). Successful separation of the enantiomers was attained, giving promising results that may cause a revolution in chiral separation, predicting the possibility of simply prepared aqueous micellar mobile phases of carrying chiral selector ability. The second motive of this work is studying the compatibility of hybrid micelle liquid mobile phases with chiral columns separating CTZ, using cellulose 1 chiral column as a model example. This study may be an environmentally safe substitute for the normal phase mode of elution that is usually applied for chiral separation consuming large amounts of hazardous organic solvents.

Block copolymer-nanodiamond coassembly in solution: towards multifunctional hybrid materials.

Polymer-nanodiamond composites are excellent candidates for the fabrication of multifunctional hybrid materials. They integrate polymer flexibility and exceptional properties of nanodiamonds (NDs), such as biocompatibility, mechanical strength, color centers, and chemically-tailored surfaces. However, their development is hindered by the challenge of ensuring that NDs are homogeneously distributed in the composites. Here, we exploit colloidal coassembly between poly(isoprene-b-styrene-b-2-vinyl pyridine) (ISV) block copolymers (BCPs) and NDs to avoid ND self-agglomeration and direct ND spatial distribution. NDs were first air oxidized at 450 °C to obtain stable dispersions in dimethylacetamide (DMAc). By adding ISV into the dispersions, patchy hybrid micelles were formed due to H-bonds between NDs and ISV. The ISV-ND coassembly in DMAc was then used to fabricate nanocomposite films with a uniform sub-50 nm ND distribution, which has never been previously reported for an ND loading (φND) of more than 50 wt%. The films exhibit good transparency due to their well-defined nanostructures and smoothness and also exhibit an improved UV-absorption and hydrophilicity compared to neat ISV. More intriguingly, at a φND of 22 wt%, ISV and NDs coassemble into a network-like superstructure with well-aligned ND strings via a dialysis method. Transmission electron microscopy and dynamic light scattering measurements suggest a complex interplay between polymer-polymer, polymer-solvent, polymer-ND, ND-solvent, and ND-ND interactions during the formation of structures. Our work may provide an important foundation for the development of hierarchically ordered nanocomposites based on BCP-ND coassembly, which is beneficial for a wide spectrum of applications from biotechnology to quantum devices.

Functionalized polymeric hybrid micelles as an efficient nanotheranostic agent for thrombus imaging and thrombolysis

Pathological thrombosis within a vessel hampers blood flow and is the mainspring of numerous fatal cardiovascular complications. In order to specifically image and dissolve a thrombus, we rationally designed a functionalized polymeric hybrid micelle (PHM) system self-assembled from amphiphilic polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethylene glycol (PCL-PEG). Based on a biological component of thrombi, activated coagulation factor XIII (FXIIIa), which is responsible for fibrin crosslinking, we further developed FXIIIa-targeted near infrared imaging and thrombolytic nanoparticles, termed IR780/FPHM/LK NPs, through chemical conjugation of peptides to the system. In a ferric chloride (FeCl3)-induced mouse carotid thrombosis model, IR780/FPHM/LK NPs specifically targeted the thrombus and significantly enhanced the photoacoustic signal for an accurate diagnosis. When loaded with the fibrinolytic drug lumbrokinase (LK), FPHM remarkably dissociated the thrombus accompanied by an increase in the d-dimer level, a fibrin degradation product, and alleviation of fatal nonspecific hemorrhagic risk. Given its thrombus-specific imaging along with potent therapeutic activities, IR780/FPHM/LK NPs hold promise for developing nanotheranostic agents in preclinical thrombotic vascular disease models.

NIR-Light-Activated Ratiometric Fluorescent Hybrid Micelles for High Spatiotemporally Controlled Biological Imaging and Chemotherapy.

Intelligent-responsive imaging-therapy strategy has shown great significance for biomedicine. However, it is still a challenge to construct spatiotemporally controlled imaging-therapy systems triggered by near infrared (NIR) light. In this work, NIR-light-activated ratiometric fluorescent hybrid micelles (RFHM) are prepared via the co-assembly of upconversion nanoparticles (UCNPs), doxorubicin (DOX), and UV-light-responsive amphiphilic block copolymer for the spatiotemporally controlled imaging and chemotherapy. Upon NIR light irradiation, UCNPs can convert NIR light to UV light. The emitted UV light induces the photoreaction of copolymer to further trigger ratiometric fluorescence imaging and degradation of hybrid micelles, resulting in rapid DOX release from hybrid micelles for antitumor therapy. The animal experiments reveal that NIR light can not only remotely regulate the ratiometric fluorescence imaging of RFHM in tumor tissue, but also trigger DOX release from RFHM to inhibit tumor growth. Therefore, this study provides a new strategy to achieve high spatial-temporal-controlled biological imaging and chemotherapy.

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.

How Detergents Dissolve Polymeric Micelles: Kinetic Pathways of Hybrid Micelle Formation in SDS and Block Copolymer Mixtures.

Mixtures of amphiphilic polymers and surfactants are used in a wide range of applications, e.g., pharmaceuticals, detergents, cosmetics, and drug delivery systems. Still, many questions remain on how the structure and, in particular, the kinetics of block copolymer micelles are affected in the presence of surfactants and what controls the solubilization kinetics. In this work, we have studied the stability and solubilization kinetics of block copolymer micelles upon the addition of the surfactant sodium dodecyl sulfate (SDS) using small-angle X-ray/neutron scattering. The ability of the surfactant to dissolve polymer micelles or form mixed micelles has been investigated using two types of amphiphilic polymers, poly(ethylene-alt-propylene)–poly(ethylene oxide) (PEP1-PEO20) and n-alkyl-functionalized PEO (C28-PEO5). The exchange kinetics of C28-PEO5 micelles are in the order of hours, while PEP1-PEO20 micelles are known to be frozen on a practical timescale. In this work, we show that the addition of SDS to PEP1-PEO20 provides virtually no solubilization, even after an extended period of time. However, upon adding SDS to C28-PEO5 micelles, we observe micellar dissolution and formation of mixed micelles occurring on the timescale of hours. Using a coexistence model of mixed and neat micelles, the SAXS data were analyzed to provide detailed structural parameters over time. First, we observe a fast fragmentation/fission step followed by a slow reorganization process. The latter process is essentially independent of concentration at low volume fraction but is greatly accelerated at larger concentrations. This might indicate a crossover from a predominance of molecular exchange to fusion/fission processes.

Synthesis of Ag/fluorine-containing polyacrylate latex stabilized by Ag nanoparticle hybrid amphiphilic random copolymer micelles via Pickering emulsion polymerization and its application on fabric finishing

Ag/fluorine-containing polyacrylate latex was successfully synthesized via Pickering emulsion polymerization using Ag/poly(2-dimethylaminoethyl methacrylate-co-hexafluorobutyl acrylate) (Ag/P(DMAEMA-co-HFBA)) hybrid micelles as particle emulsifiers. The influences of introducing the Ag nanoparticles (NPs) component and the concentration of Ag/P(DMAEMA-co-HFBA) hybrid micelles on emulsion polymerization and finished cotton fabric properties were studied. The results showed that the Ag/fluorine-containing polyacrylate latex had a higher conversion, smaller particle size than the fluorine-containing polyacrylate latex using P(DMAEMA-co-HFBA) micelles as emulsifiers, indicating the positive effect of Ag NPs on emulsion polymerization. And thermogravimetric analysis (TGA) proved that Ag NPs improved the thermal stability of the latex film. Moreover, the surface of the cotton fabric finished by Ag/fluorine-containing polyacrylate latex showed more rough morphology, better hydrophobicity and excellent antibacterial activity owing to the synergistic effect of the cationic fluorine-containing polyacrylate compounds and Ag nanoparticles. Meanwhile, the presence of Ag NPs also improved the tensile strength of the finished cotton fabric, but reduced slightly the whiteness. When the concentration of Ag/P(DMAEMA-co-HFBA) hybrid micelle emulsifier was 8 mg/mL, the Ag/fluorine-containing polyacrylate latex particles presented regular raspberry-shaped with an average diameter of 120 nm, and the water/oil contact angles of finished cotton fabric attained 145° and 90°, respectively. In addition, the finished cotton fabric exhibited excellent antibacterial properties against both S. aureus and E. coli as the concentration of Ag/P(DMAEMA-co-HFBA) hybrid micelles was 12 mg/mL. The mechanism for the formation of Ag/fluorine-containing polyacrylate latex was proposed.

Studying the effect of vasopressors on therapeutic drug monitoring of two local anesthetics using hybrid micelle liquid chromatography as an analysis tool

A hybrid micelle based mobile phase was used to develop and validate a liquid chromatographic method for the separation and quantification of two local anesthetics namely; lidocaine hydrochloride (LID), and bupivacaine hydrochloride (BPV) in presence of the frequently co administered vasopressors phenyl ephrine (PHR) and ephedrine (EPH). Optimization of chromatographic separation conditions was performed applying experimental one factor at a time tool, and design of experiment, where the retention behavior of all analytes using both optimization protocols was in accordance. Chromatographic separation was carried on a C8 column operating at 40 °C at a flow rate of 1.5 mL/min. using a mobile phase consisting of 0.18 M sodium dodecyl sulphate, 10% acetonitrile, containing 0.3% triethyl amine and adjusted to pH 7 using 2 M ortho phosphoric acid, adopting UV detection at 230 nm. The proposed method was fully validated and applied to both in vitro and in vivo analysis of rat blood samples. The pharmacokinetics of both LID and BPV was followed when they were solitary injected or when co administered with either PHR or EPH. Moreover, the in vitro spiked experiment was also subjected to documented bio-analytical validation procedures.

Hybrid micelles based on Pt (IV) polymeric prodrug and TPGS for the enhanced cytotoxicity in drug-resistant lung cancer cells

Multidrug resistance (MDR) is a primary cause of failure in oncotherapy and interest is growing in the design of multi-stimuli responsive nano-carriers to synergistically deliver chemotherapeutic agents and P-gp inhibitors to reverse MDR. The hybrid micelles based on a Platinum (IV)-coordinate polymeric prodrugs and TPGS were developed to improve chemotherapy and reduce side effects. The pH/redox dual-sensitive polymers were synthesized by condensation polymerization using ortho ester monomer and diamminedichlorodisuccinatoplatinum (DSP). The hybrid micelles possessed uniform size (38 nm) and displayed good stability in various physiological conditions. In contrast, in vitro drug release profiles indicated that these micelles could be completely depolymerized under acidic and reducing environment, thereby more than 80 % cisplatin were released within 12 h at pH 5.0 plus 10 mM DTT. More importantly, a large amount of TPGS released simultaneously could effectively inhibit the function of drug efflux pumps, which significantly enhanced the cytotoxicity of cisplatin against A549/DDP cells. The growth inhibition rate of micelles on A549/DDP multicellular spheroids was 79.5 %, while that of free cisplatin was only 6.8 %. Therefore, these hybrid micelles are promising in overcoming tumor MDR and worth doing further research in vivo and extend to other therapeutic agents.

Analysis of some pharmaceuticals in the presence of their synthetic impurities by applying hybrid micelle liquid chromatography

AbstractA stability-indicating hybrid micelle liquid chromatography accompanied by UV detection was developed for the simultaneous analysis of either paracetamol (PCA) or pseudoephedrine hydrochloride (PSU) with their synthetic impurities. Mixture I contains PCA withp-amino phenol andp-nitro phenol, while mixture II involves the estimation of PSU with benzaldehyde and benzoic acid. Both mixtures were separated using a C18 column that was thermostatically maintained at 40°C and operating under a flow rate of 1.5 mL/min, applying UV detection at 240 nm for mixture I and 220 nm for mixture II. In both cases, the mobile phase consisted of 0.1 M sodium dodecyl sulfate, acetonitrile, and triethylamine (90:10:0.3, v/v/v) and adjusted to pH 4 (mixture I) or pH 3.7 (mixture II) using 2.0 MO-phosphoric acid. The proposed method was validated and successfully applied to assay different pharmaceuticals containing PCA or PSU. Moreover, the stability-indicating nature of the proposed method was proved through applying photolytic degradation procedures for PCA.

Pluronic micelles with suppressing doxorubicin efflux and detoxification for efficiently reversing breast cancer resistance

The antitumor activity of doxorubicin (DOX) is often limited owing to the occurrence of multidrug resistance (MDR) during treatment. Herein, we developed hybrid polymeric micelles, which consisted of pluronic F127 as long-circulating helper in blood, and phenylboronic ester-grafted pluronic P123 (PHE) as efflux and detoxification regulator to efficiently deliver DOX and reverse MDR in vivo. Hybrid F127/PHE micelles exhibited higher stability and drug encapsulation (~80%) than simple F127/P123 micelles due to its lower CMC, and displayed in vitro drug release in a hydrogen peroxide (H2O2)-sensitive manner. Besides, DOX-loaded hybrid micelles (F127/PHE-DOX) possessed higher cell-killing ability and induce more apoptotic in MDR-cells than other groups, which was probably because it not only could greatly increase intracellular drug concentration by inhibiting P-gp mediated drug efflux, but also promote reactive oxygen species (ROS) generation by decreasing glutathione (GSH) levels. Besides, in vivo evaluation indicated that F127/PHE-DOX could well accumulate at tumor regions and exhibit the strongest tumor growth inhibition (TGI 87.87%) accompanied with low side effects. As a result, F127/PHE micelles had great potentials as a platform for anticancer drugs delivery and tumor MDR reversal in clinical application.

Block copolymer micelles confined in cylindrical nanopores: Effects of annealing solvents and hybridization

Amphiphilic block copolymer micelles have been intensively investigated and applied into various research fields for decades. One of the most promising characteristics for block copolymer micelles is the selective incorporation of metal precursors in the cores or coronas of the micelles. By combining with nanoporous membranes, aligned polymer nanostructures can be generated, facilitating the applications such as nanolithography and catalysis. The morphology transitions and controllability of block copolymer micelles in confined geometries, however, have seldom been studied. In addition, for hybrid micelles in which polymer segments are selectively incorporated with inorganic metal precursors, the relationship between hybridization and morphologies of polymer nanostructures in the confined states is still under discussion. In this work, we investigate the effects of annealing solvents and hybridization with metal precursors (gold(III) chloride trihydrate (HAuCl4 · 3H2O)) on the morphologies of polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer micelles confined in the nanopores of anodic aluminum oxide (AAO) templates. Tuned by the annealing solvent vapors and the selective ion complexation between HAuCl4 and P4VP cores, various morphologies can be effectively controlled, such as the spherical-micelles-in-rod morphology, the parallel-cylinders-in-rod morphology, and the hemispherical-micelles-in-rod morphology. This study not only investigates the effects of annealing solvent vapors and hybridization on the morphologies of block copolymer micelles confined in cylindrical nano-geometries but also offers a viable route for preparing metal nanoparticles embedded in porous templates.

Dual and Multi-Emission Hybrid Micelles Realized through Coordination-Driven Self-Assembly.

Building novel functional nanomaterials with a polymer is one of the most dynamic research fields at present. Here, three amphiphilic block copolymers of 8-hydroxyquinoline derivative motifs (MQ) with excellent coordination function were synthesized by Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) polymerization. The coordination micelles were prepared through the self-assembly process, which the MQ motifs were dispersed in the hydrophobic polystyrene (PSt) blocks and hydrophilic Poly(N-isopropylacrylamide (PNIPAM)) blocks, respectively. The dual-emission micelles including the intrinsic red light emission of quantum dots (QDs) and the coordination green light emission of Zn2+-MQ complexes were built by introducing the CdSe/ZnS and CdTe/ZnS QDs in the core and shell precisely in the coordination micelles through the coordination-driven self-assembly process. Furthermore, based on the principle of three primary colors that produce white light emission, vinyl carbazole units (Polyvinyl Carbazole, PVK) with blue light emission were introduced into the hydrophilic PNIPAM blocks to construct the white light micelles that possess special multi-emission properties in which the intrinsic red light emission of QDs, the coordination green light of Zn2+-MQ complexes, and the blue light emission of PVK were synergized. The dual and multi-emission hybrid micelles have great application prospects in ratiometric fluorescent probes and biomarkers.

Preparation and antitumor evaluation of hinokiflavone hybrid micelles with mitochondria targeted for lung adenocarcinoma treatment

Hinokiflavone (HF) is a natural biflavonoid extracted from medicinal plants such as Selaginella tamariscina and Platycladus orientalis. HF plays a crucial role in the treatment of several cancers. However, its poor solubility, instability, and low bioavailability have limited its use. In this study, soluplus/d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS)/dequalinium (DQA) was applied to improve the solubilization efficiency and stability of HF. HF hybrid micelles were prepared via thin-film hydration method. The physicochemical properties of micelles, including particle size, zeta potential, encapsulation efficiency, drug loading, CMC value, and stability were investigated. The in vitro cytotoxicity assay showed that the cytotoxicity of the HF hybrid micelles was higher than that of free HF. In addition, the HF hybrid micelles improved anticancer efficacy and induced mitochondria-mediated apoptosis, which is associated with the high levels of ROS inducing decreased mitochondrial membrane potential, promoting apoptosis of tumor cells. Furthermore, in vivo tumor suppression, smaller tumor volume and increased expression of pro-apoptotic proteins were found in nude mice treated with HF hybrid micelles, suggesting that HF hybrid micelles had stronger tumor suppressive activity compared with free HF. In summary, HF hybrid micelles developed in this study enhanced antitumor effect, which may be a potential drug delivery system for the treatment of lung adenocarcinoma.