Amphiphilic Block Copolymer Poly Research Articles

Multigeometry Nanoparticles: Hybrid Vesicle/Cylinder Nanoparticles Constructed with Block Copolymer Solution Assembly and Kinetic Control

We report an experimental study of the assembly of various multicompartment and multigeometry nanoparticles constructed from mixtures of two diblock copolymers. By simply blending the amphiphilic block copolymers poly(acrylic acid)-block-polyisoprene (PAA-b-PI) and poly(acrylic acid)-block-polystyrene (PAA-b-PS), we constructed complex nanostructures including multigeometry vesicle–cylinder particles, multicompartment vesicles, or multigeometry cylinder–disk nanoparticles via kinetic control of solution assembly. In our assembly strategy, the PAA common domain in both block copolymers was first complexed with organic diamine molecules in organic solution to form a particle core. Therefore, the two different hydrophobic blocks from the two different polymers were trapped into the same particle. After addition of water, the particles form the structure having hydrophobic cores and PAA-amine hydrophilic shells; the two hydrophobic domains locally nanophase-separated in the core to form the multicompartment a...

Iridium Oxide Coatings with Templated Porosity as Highly Active Oxygen Evolution Catalysts: Structure-Activity Relationships.

Iridium oxide is the catalytic material with the highest stability in the oxygen evolution reaction (OER) performed under acidic conditions. However, its high cost and limited availability demand that IrO2 is utilized as efficiently as possible. We report the synthesis and OER performance of highly active mesoporous IrO2 catalysts with optimized surface area, intrinsic activity, and pore accessibility. Catalytic layers with controlled pore size were obtained by soft-templating with micelles formed from amphiphilic block copolymers poly(ethylene oxide)-b-poly(butadiene)-b-poly(ethylene oxide). A systematic study on the influence of the calcination temperature and film thickness on the morphology, phase composition, accessible surface area, and OER activity reveals that the catalytic performance is controlled by at least two independent factors, that is, accessible surface area and intrinsic activity per accessible site. Catalysts with lower crystallinity show higher intrinsic activity. The catalyst surface area increases linearly with film thickness. As a result of the templated mesopores, the pore surface remains fully active and accessible even for thick IrO2 films. Even the most active multilayer catalyst does not show signs of transport limitations at current densities as high as 75 mA cm(-2) .

RAFT radical copolymerization of beta‐pinene with maleic anhydride and aggregation behaviors of their copolymer in aqueous solution

ABSTRACTRAFT copolymerization of beta‐pinene and maleic anhydride was successfully achieved for the first time, using 1‐phenylethyl dithiobenzoate as chain transfer agent in a mixed solvent of tetrehydrofuran and 1.4‐dioxane (1:9, v/v) at a feed molar ratio of beta‐pinene to maleic anhydride as 3:7, and the alternating copolymer was prepared with predetermined molecular weight and narrow molecular weight distribution. Furthermore, using former alternating copolymer as a macro‐RAFT agent, block copolymer poly(beta‐pinene‐alt‐maleic anhydride)‐b‐polystyrene was synthesized in a chain extending with styrene. Hydrolysis of this block copolymer under acidic conditions formed a new amphiphilic block copolymers poly(beta‐pinene‐alt‐maleic acid)‐b‐polystyrene whose self‐assembly behaviors in aqueous solution at different pH were investigated through SEM and DLS. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1422–1429

Synthesis and Photophysical Property of Polyion Complex Micelle Incorporating Phthalocyanine Zinc(II) Bearing Benzyl Ether Dendritic Substituents with Nitro-Terminal Group

A new phthalocyanine Zinc(II) bearing benzyl ether dendritic substituents with nitro-terminal group: tetra-{3,5-[di-(4-nitro benzyloxy) benzyloxy]} Phthalocyanine Zinc(II) (ZnPc(NO2)8), was synthesis and characterized by IR, 1HNMR, MALDI-TOF-MS and UV/Vis. UV/Vis spectra of ZnPc(NO2)8 exhibited characteristic absorption peaks at 290, 350 and 680 nm, and fluorescence emission peak was at 692 nm with a quantum yield at 0.20 in dimethylsulfoxide (DMSO). The polymeric nanoparticle ZnPc(NO2)8@MPEG-PLGA was formed between the amphiphilic block copolymer poly(ethylene glycol)-polylactic and polyglyctic acids (PEG-PLGA) and ZnPc(NO2)8, ZnPc(NO2)8@MPEG-PLGA formed a core-shell-type nanoparticle with diameter about 70 nm. UV/Vis spectra and fluorescence emission spectra of ZnPc(NO2)8@MPEG-PLGA were obviously lower than that of free ZnPc(NO2)8 in buffer solution, and with varying degrees of redshift. ZnPc(NO2)8@MPEG-PLGA would be a promising third-generation photosensitizer for PDT.

Amphiphilic block copolymer terminated with pyrene group: from switchable CO2-temperature dual responses to tunable fluorescence

Py-PCL-b-P(NIPAM-co-DMAEMA) micelles can present switchable CO2-temperature dual responses and tunable fluorescence properties.

Ring assembly of silica nanospheres mediated by amphiphilic block copolymers with oxyethylene moieties

Amphiphilic block copolymers poly[(2-ethoxyethyl vinyl ether)-block-(2-methoxyethyl vinyl ether)] (EOVE-b-MOVE) induce the ring assembly of silica nanospheres (SNSs, ca. 15 nm) in the liquid phase. Nanorings form with appropriate polymer concentration, pH and temperature. EOVE-b-MOVEs with varying block lengths successfully induce the ring assembly of SNSs, whereas a random copolymer fails, indicating that polymer’s molecular structure critically affects the assembly mode of SNSs. Interestingly, SNSs of a larger size (ca. 30 nm) one-dimensionally assemble into nanochains with these block copolymers under otherwise identical conditions.

Amphiphilic block copolymer poly(2-methacryloyloxyethyl phosphorylcholine) and poly(trimethylene carbonate): Preparation and for intracellular drug delivery

A robust redox-responsive block copolymer was proposed and prepared as drug vehicle based on disulfide linked poly(2-methacryloyloxyethyl phosphorylcholine) and poly(trimethylene carbonate) (PMPC-ss-PTMC). The size and morphology of the polymer nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The profile of drug release response to glutathione (GSH) was monitored in vitro. Upon 10 mM GSH, mimicking the intracellular microenvironments such as cytosol and the cell nucleus, the resulted drug carrier was destructed ascribe to abruption of the disulfide bonds, followed by accelerated drug release from the nanoparticles. MTT assay showed that the blank micelles did not reveal cytotoxicity to the human cervical cancer HeLa cells and mouse connective tissue fibroblast L929 cells even up to 500 μg/mL. On the other hand, the Doxorubicin-loaded (DOX-loaded) micelles that contained disulfide bonds exhibit a higher cytotoxicity against HeLa cells than that of no disulfide bonds, but there was no significant difference in cytotoxicity against the L929 cells. Confocal laser scanning microscopy and flow cytometry investigation showed that the DOX-loaded micelles can be swiftly internalized, and effectively transmitted the drugs into nuclei. These results suggested that the copolymer as a robust and effective redox-responsive nanocarrier to augment drug efficacy for cancer cells.

Transferrin-targeted magnetic/fluorescence micelles as a specific bi-functional nanoprobe for imaging liver tumor.

In order to delineate the location of the tumor both before and during operation, we developed targeted bi-functional polymeric micelles for magnetic resonance (MR) and fluorescence imaging in liver tumors. Hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) were loaded into the polymeric micelles through self-assembly of an amphiphilic block copolymer poly(ethylene glycol)-poly(ϵ-caprolactone). After, transferrin (Tf) and near-infrared fluorescence molecule Cy5.5 were conjugated onto the surface of the polymeric micelles to obtain the nanosized probe SPIO@PEG-b-PCL-Tf/Cy5.5 (SPPTC). Imaging capabilities of this nanoprobe were evaluated both in vitro and in vivo. The accumulation of SPPTC in HepG2 cells increased over SPIO@PEG-b-PCL-Cy5.5 (SPPC) by confocal microscopy. The targeted nanoprobe SPPTC possessed favorable properties on the MR and fluorescence imaging both in vitro and in vivo. The MTT results showed that the nanoprobes were well tolerated. SPPTC had the potential for pre-operation evaluation and intra-operation navigation of tumors in clinic.

Tertiary amine block copolymer containing ultrafiltration membrane with pH-dependent macromolecule sieving and Cr(VI) removal properties

To obtain ultrafiltration (UF) membranes with multi-functions in permeation, macromolecule sieving and specific heavy metal removal by adsorption, tertiary amine groups containing amphiphilic block copolymers (poly(methyl methacrylate-b-dimethylamino-2-ethyl methacrylate) (P(MMA-b-DMAEMA))) were designed and synthesized. Then the block copolymers were used to fabricate the tertiary amine block copolymer containing blend membranes with poly(vinylidene fluoride) (PVDF) via a non-solvent induced phase separation (NIPS) process. Hydrogen nuclear magnetic resonance (1H NMR) and X-ray photoelectron spectroscopy (XPS) were used to characterize the bulk and the surface layer compositions of the prepared membranes. It was found that P(MMA-b-DMAEMA) stably retained in the blend membranes and greatly enriched onto the surface layers. The pH-dependent performances of the membranes were investigated in details. With the change of pH values, the surface hydrophilicity, water permeation, dextran sieving behaviors and hexavalent chromium (Cr(VI)) adsorption properties varied greatly. And the membrane performed obviously reversible pH-dependent property. From the results, a feasible method could be inferred for fabricating UF membranes with tunable filtration, macromolecule sieving and anion adsorption properties under different pH conditions.

Large compound vesicles from amphiphilic block copolymer/rigid-rod conjugated polymer complexes.

Morphology evolution in complexes of amphiphilic block copolymers poly(styrene)-b-poly(acrylic acid) (PS-b-PAA) and poly(styrene)-b-poly(ethylene oxide) (PS-b-PEO) in the presence of polyaniline (PANI) in aqueous solution is reported. Transmission electron microscopy, atomic force microscopy, and dynamic light scattering techniques were used to study the morphologies at various PANI contents [aniline]/[acrylic acid] ([ANI]/[AA]) ranging from 0.1 to 0.7. The interpolyelectrolyte complex formed between PAA and PANI plays a key role in the morphology transformation. Spherical micelles formed from pure block copolymers were transformed into large compound vesicles upon increasing PANI concentration due to internal block copolymer segregation. In addition to varying PANI content, the kinetic pathway of nanoparticle formation was controlled through different water addition methods and was critical in the formation of multigeometry nanoparticles.

Photocatalytic applications with CdS • block copolymer/exfoliated graphene nanoensembles: hydrogen generation and degradation of Rhodamine B

Amphiphilic block copolymer poly(isoprene-b-acrylic acid) (PI-b-PAA) was used to stabilize exfoliated graphene in water, allowing the immobilization of semiconductor CdS nanoparticles forming CdS • PI-b-PAA/graphene. Characterization using high-resolution transmission electron microscopy and energy-dispersive x-ray spectroscopy proved the success of the preparation method and revealed the presence of spherical CdS. Moreover, UV–Vis and photoluminescence assays suggested that electronic interactions within CdS • PI-b-PAA/graphene exist as evidenced by the significant quenching of the characteristic emission of CdS by exfoliated graphene. Photoillumination of CdS • PI-b-PAA/graphene, in the presence of ammonium formate as a quencher for the photogenerated holes, resulted in the generation of hydrogen by water splitting, monitored by the reduction of 4-nitroaniline to benzene-1,4-diamine (>80 ± 4% at 20 min; 100% at 24 min), much faster and more efficient compared to when reference CdS • PI-b-PAA was used as the photocatalyst (<30 ± 3% at 20 min; 100% at 240 min). Moreover, Rhodamine B was photocatalytically degraded by CdS • PI-b-PAA/graphene, with fast kinetics under visible light illumination in the presence of air. The enhancement of both photocatalytic processes by CdS • PI-b-PAA/graphene was rationalized in terms of effective separation of holes and electrons, contrary to reference CdS • PI-b-PAA, in which rapid recombination of the hole–electron pair is inevitable due to the absence of exfoliated graphene as a suitable electron acceptor.

Luminescent nanoparticles with lanthanide-containing poly(ethylene glycol)-Poly(ε-caprolactone) block copolymers.

Lanthanide-containing nanoparticles have attracted much attention due to their unique optical properties and potential in nanotechnological applications. An amphiphilic block copolymer of poly(ethylene glycol)-b-poly(ε-caprolactone) methyl ether (mPEG-PCL) was functionalized with a dipicolinic acid (dpa) moiety and coordinated to lanthanide ions to afford [Ln(dpa-PCL-PEG-OCH3)3](HNEt3)3 (Ln = Eu(3+), Tb(3+)). Micelle-like nanoparticles of dpa-PCL-PEG-OCH3 macroligand and metal-centered polymers were prepared by solvent displacement methods. Dynamic light scattering analysis (DLS) and cryogenic transmission electron microscopy images confirmed the presence of solid sphere (<47 nm in diameter) and vesicle (>47 nm in diameter) morphologies. The viability and stability of the lanthanide complexes in micelle-like nanoparticles was explored by DLS and luminescence spectroscopy, and found to be stable for several weeks.

Tumor-acidity activated surface charge-conversion of polymeric nanocarriers for enhanced cell adhesion and targeted drug release.

The development of stimuli-responsive polymeric nanocarriers could significantly enhance drug bioavailability due to improved pharmacokinetics and biodistribution. However, in the drug delivery process, the poor cell uptake of drug-loaded carriers has greatly limited the therapeutic efficiency for anti-cancer applications. Herein, 2,3-dimethylmaleic anhydride (DMMA) is engineered into the well-defined biodegradable amphiphilic block copolymer poly(D,L-lactide)-block-poly(2-aminoethyl methacrylate) (PLA-b-PAEMA) to construct a tumor-acidity activated nanocarrier (PLA-b-PAEMA/DMMA) for potential tumor therapy. After the loading of positively charged DOX·HCl into the negatively charged corona structure through electrostatic attraction, this carrier is expected to prolong the blood circulation time and smartly convert surface charge from negative to positive for enhanced tumor cell uptake and targeted drug release. Furthermore, this carrier exhibits additional cytotoxicity for tumor cells after the tumor-acidity activated surface charge-conversion from negative to positive. Thus, this smart carrier is a feasible candidate for potential cancer therapy.

Hemocompatibility and ultrafiltration performance of surface-functionalized polyethersulfone membrane by blending comb-like amphiphilic block copolymer

While polyethersulfone (PES) represents outstanding oxidative, thermal and hydrolytic stability as well as good mechanical and film-forming properties, the hemocompatibility of PES membrane must be dramatically enhanced to reduce injections of anticoagulants during hemodialysis. In this study, a comblike amphiphilic block copolymer poly (vinyl pyrrolidone)-block-poly (acrylate-graft-poly (methyl methacrylate))-block-poly-(vinyl pyrrolidone) (PVP-b-P(AE-g-PMMA)-b-PVP) was synthesized via reversible addition-fragmentation chain transfer polymerization and used to modify PES membrane via a liquid–liquid phase separation technique. The surface structure of the modified membrane were characterized by using X-ray photoelectron spectroscopic analysis, fourier transform infrared and water contact angle measurement. The modified PES membrane showed low hemolysis ratio, improved hydrophilicity, suppressed platelet adhesion and prolonged activated partial thromboplastin time. And the modified membranes showed high PBS solution (or water) flux and good protein anti-fouling properties. The dramatic performance enhancement is attributed to its unique surface architecture, which may be formed by migration and self-assembly of PVP-b-P(AE-g-PMMA)-b-PVP during phase separation. In the surface layer of the modified membrane, PVP chain formed functional brush while PMMA chain embedded in the membrane substrate. The highly branched chains of P(AE-g-PMMA) block endowed the modified membrane with good stability, which has potential to be used in blood purification.

Stabilization of nano-TiO2 aqueous dispersions with poly(ethylene glycol)-b-poly(4-vinyl pyridine) block copolymer and their incorporation in photocatalytic acrylic varnishes

Abstract In this work, TiO 2 nanoparticles were dispersed and stabilized in water using a novel type of dispersant based on tailor-made amphiphilic block copolymers of poly(ethylene glycol)-block-poly(4-vinyl pyridine) (mPEG- b -P4VP) prepared by atom transfer radical polymerization (ATRP). The performance of this new block copolymer as dispersant was compared to a polyelectrolyte dispersant commonly used for TiO 2 , sodium salt of polyacrylic acid (Na-PAA). The effect of dispersion technique and type and amount of dispersant on deagglomeration and stability of the TiO 2 aqueous suspensions were studied. After incorporation in a standard waterborne acrylic varnish formulation, dry film transparency, photocatalytic activity, and nanoparticle cluster size were also evaluated. The results show that mPEG- b -P4VP copolymer with appropriate block lengths can have a better performance than Na-PAA in terms of aqueous dispersion stabilization and cluster size reduction in the acrylic matrix. This translates into higher film transparency and photocatalytic performance.

Study on stimuli responsive complex micelles prepared by hydrogen bonding interactions

Two amphiphilic block copolymers poly(t-butyl acrylate)-b-poly(N-isopropylacrylamide) and poly(t-butyl acrylate)-b-poly[2-(dimethylamino)ethyl methacrylate] (PtBA-b-PDMAEMA) were synthesised by atom transfer radical polymerisation reaction. Then, PtBA-b-PDMAEMA was hydrolysed to prepare poly(acrylic acid)-b-poly[2-(dimethylamino) ethyl methacrylate] in an acidic medium. 1H NMR spectroscopy was used to characterise the chemical structure of the block copolymers. The complex micelles were prepared under the condition of 25°C and pH 5·5. It has been found that their stimuli response behaviour changed with different temperature and pH in solutions which were investigated by a Zetasizer Nano ZS Instrument. The morphology of complex micelles was characterised by TEM. Core shell structure and corona of the micelles were observed obviously from the TEM images. Moreover, the hydrogen bonding interaction in complex micelles was studied by Fourier transform infrared spectroscopy.

Biosensor utilizing a liquid crystal/water interface functionalized with poly(4-cyanobiphenyl-4′-oxyundecylacrylate-b-((2-dimethyl amino) ethyl methacrylate))

The interface between the nematic liquid crystal, 4-cyano-4′-pentylbiphenyl (5CB) and water within a transmission electron microscopy (TEM) grid cell coated with the pH-dependent weak cationic amphiphilic block copolymer poly((4-cyanobiphenyl-4′-oxyundecylacrylate)-b-((2-dimethyl amino) ethyl methacrylate)) (LCP-b-PDMAEMA) (which was successfully synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization) was subsequently evaluated for protein and deoxyribonucleic acid (DNA) detection. The LCP-b-PDMAEMA monolayer was fabricated using a Langmuir Blodgett trough, transferred to the 5CB-filled TEM grid, and placed on the octadecyltrichlorosilane-coated glass (TEMPDMAEMA) in such a way that the LCP chains were immersed in the 5CB while the PDMAEMA chains were pointed away from the 5CB surface and immersed in water. Several model proteins such as bovine serum albumin (BSA), hemoglobin (Hb), and chymotrypsinogen (ChTg) were tested at pH values ranging from 2 to 12 to determine the role of the charge state of the protein on protein detection by a weak polyelectrolyte such as PDMAEMA. PDMAEMA contains cationic and neutral states below and above the pKa value, respectively, and is thus able to absorb proteins below its pKa threshold through electrostatic interactions. BSA exhibited a homeotropic to planar (H–P) change in orientation within the TEMPDMAEMA grid cell at concentrations greater than 0.02wt% within the pH range between the isoelectric point (pI) of BSA and the pKa of PDMAEMA, where the charge states of BSA and PDMAEMA were negative and positive, respectively. However, this change in orientation did not occur with other proteins that exhibited a pI higher than the pKa of PDMAEMA due to the electrostatic repulsions resulting from their same cationic charges. This result indicates that the electrostatic interactions between proteins and PDMAEMA are a major contributing factor for protein detection by the H–P transformation within the TEMPDMAEMA grid cell. DNA, a pH-independent strong anionic polyelectrolyte, was also tested with the TEMPDMAEMA grid cell, and it exhibited an H–P transformation at the charged state of PDMAEMA below its pKa threshold at concentrations higher than 0.01wt%. Thus, we demonstrated that the TEMPDMAEMA grid cell effectively facilitated the detection of negatively charged biomaterials (i.e.; protein and DNA) through the H–P transformation using the polarized optical microscope. This simple and inexpensive experimental set-up for non-specific biomaterial detection lays the basic groundwork for developing effective biosensors using polyelectrolytes.

Thermo-triggered drug delivery from polymeric micelles of poly(N-isopropylacrylamide-co-acrylamide)-b-poly(n-butyl methacrylate) for tumor targeting

Novel temperature-sensitive micelles, possessing a core-shell structure, were successfully fabricated and evaluated as possible systems for targeting anticancer drugs to solid tumors. The amphiphilic block copolymer poly( N-isopropylacrylamide- co-acrylamide)-b-poly( n-butyl methacrylate) was used to achieve a stimuli-responsive on/off release and spatial specificity. The anticancer drug methotrexate, which is poorly water soluble, was used as the model. Fourier transform–infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel-permeation chromatography, and critical micelle concentration were used to evaluate the successful synthesis of block copolymers with a lower critical solution temperature ~40°C. Based on transmission electron microscope images, the micelles are spherical particles with narrow size distribution. The thermally triggered release of methotrexate was observed in vitro. Quartz crystal microbalance with dissipation was used to investigate the interactions of the polymeric micelles with bovine serum albumin, to illustrate protein adsorption and cell attachment. Cytotoxicity studies were conducted on Lewis lung carcinoma cells, and the anticancer activity of methotrexate-loaded micelles was significantly enhanced in combination with hyperthermia. The thermo-sensitive characteristics of the micelles make them applicable as smart drug delivery systems, when combined with localized hyperthermia.

A dual ligand targeted nanoprobe with high MRI sensitivity for diagnosis of breast cancer

Antibody targeted delivery is an effective strategy to improve the diagnostic imaging outcome of nanoscale imaging agents in the focal areas. Dual targeting micelles encapsulating superparamagnetic iron oxide were prepared from the amphiphilic block copolymer poly(ethylene glycol)-poly(ɛ-caprolactone) (PEG-b-PCL) with different targeting ligands cRGD and scFv-ErbB single chain antibody conjugated to the distal ends of PEG block. The breast cancer animal model was established by subcutaneous injecting the BT474 cells into the BALB/c-nu female nude mice and then employed to assess the potential of the dual ligand targeted magnetic micelles as a novel MRI contrast agent on a 1.5 T clinical MRI scanner. The T2 signal intensity of the tumor in animals receiving the dual ligand targeted magnetic micelles via tail vein decreased more significantly than the single ligand targeted and nontargeted magnetic micelles. These results indicate that the dual ligand targeted magnetic micelles, cRGD/scFv-ErbB-PEG-PCL-SPION, have great potential to act as a new type of effective nanoscale MRI contrast agent for early diagnosis of breast cancer.

Synthesis, characterization, and temperature‐responsive behaviors of novel hybrid amphiphilic block copolymers containing polyhedral oligomeric silsesquioxane

Organic/inorganic hybrid amphiphilic block copolymer poly(methacrylate isobutyl POSS)‐b‐poly(N‐isopropylacrylamide‐co‐oligo(ethylene glycol) methyl ether methacrylate) (PMAPOSS‐b‐P(NIPAM‐co‐OEGMA)) was synthesized via reversible addition–fragmentation chain transfer polymerization. The self‐assembly behavior of this block copolymer in aqueous solution was investigated by dynamic light scattering (DLS) and transmission electron microscopy. The results indicate that the novel block copolymer can self‐assemble into spherical micelles with PMAPOSS segment as the hydrophobic part and P(NIPAM‐co‐OEGMA) segment as the hydrophilic part. The temperature‐responsive characteristics of the assemblies were tested by UV–Vis spectra and DLS. Some factors such as the concentration, molecular weight, and copolymer generation that may affect the cloud point were studied systematically. The results reveal that this copolymer exhibits a sharp and intensive lower critical solution temperature (LCST). The essentially predetermined LCST can be conveniently achieved by adjusting the content of NIPAM or OEGMA domain. In addition, these novel hybrid micelles can undergo an association/disassociation cycle with the heating and cooling of solution and the degree of reversibility displaying a tremendous concentration dependence, as a novel organic/inorganic hybrid material with distinctive virtues can be potentially used in biological and medical fields, especially in drug nanocarriers for targeted therapy. Copyright © 2014 John Wiley &amp; Sons, Ltd.