Block Copolymer Micelles Research Articles

Amphiphilic Block Copolymers: Their Structures, and Self-Assembly to Polymeric Micelles and Polymersomes as Drug Delivery Vehicles.

Self-assembly of amphiphilic block copolymers display a multiplicity of nanoscale periodic patterns proposed as a dominant tool for the 'bottom-up' fabrication of nanomaterials with different levels of ordering. The present review article focuses on the recent updates to the self-association of amphiphilic block copolymers in aqueous media into varied core-shell morphologies. We briefly describe the block copolymers, their types, microdomain formation in bulk and micellization in selective solvents. We also discuss the characteristic features of block copolymers nanoaggregates viz., polymer micelles (PMs) and polymersomes. Amphiphilic block copolymers (with a variety of hydrophobic blocks and hydrophilic blocks; often polyethylene oxide) self-assemble in water to micelles/niosomes similar to conventional nonionic surfactants with high drug loading capacity. Double hydrophilic block copolymers (DHBCs) made of neutral block-neutral block or neutral block-charged block can transform one block to become hydrophobic under the influence of a stimulus (physical/chemical/biological), and thus induced amphiphilicity and display self-assembly are discussed. Different kinds of polymer micelles (viz. shell and core-cross-linked, core-shell-corona, schizophrenic, crew cut, Janus) are presented in detail. Updates on polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are also provided. Polyion complexes (PICs) and polyion complex micelles (PICMs) are discussed. Applications of these block copolymeric micelles and polymersomes as nanocarriers in drug delivery systems are described.

Encapsulation of Nanoparticles into Preformed Block Copolymer Micelles Driven by Competitive Solvation: Experimental Studies and Molecular Dynamic Simulations

We investigate the encapsulation of polymer-tethered nanoparticles (NPs) inside block copolymer (BCP) micelles, which turns to the mutual stabilization of BCP micelles and NPs by each other. It has been demonstrated, for the first time, that in the presence of cosolvent, which is selective for the core-forming block, the encapsulation of polymer-tethered NPs into the core of preformed BCP micelles is feasible. Furthermore, interestingly, in a certain range of cosolvent volume fraction, NP/BCP hybrid micelles comprising a single NP in the micelle core could be obtained. Significantly, in the presence of cosolvent the NP-loaded hybrid micelles remain intact, whereas the NP-free (empty) micelles undergo further transformations. The experimental observations are additionally supported by the results obtained from the molecular dynamic simulation. In particular, our modeling recognizes mechanisms for the formation of NP/BCP hybrids, which include a one-by-one adsorption of individual BCP chains onto the NP surface, fusion of NP with the preformed BCP micelles, or a combination of both mechanisms. The present work provides new opportunities for the fabrication of BCP-based hybrid nanomaterials having potential applications in drug delivery, diagnostics, catalysis, energy harvesting materials, optical devices, etc.

Phase Control of Colloid-like Block Copolymer Micelles by Tuning Size Distribution via Thermal Processing

The formation of a Frank–Kasper (FK) phase in a one-component block copolymer (bcp) has been attributed to the sufficiently large conformational asymmetry parameter that leads to the deformation of the micellar core into the polyhedral shape templated by the Voronoi cells for relieving the packing frustration of the coronal blocks. Here we present the insight into the evolution of body-centered cubic (BCC) and Laves C14 phases from the corresponding metastable liquidlike packing (LLP) phases in a conformationally symmetric poly(2-vinylpyridine)-block-poly(dimethylsiloxane) (P2VP-b-PDMS) forming the colloid-like micelle with a hard P2VP core and a soft PDMS corona at the temperature of micelle ordering (Tgcorona < Ta < Tgcore). Different thermal processing conditions were applied to produce four distinct types LLP phase characterized by different average micelle size and size dispersity. The LLP phase was found to transform to BCC, C14 and a reorganized LLP phase with increasing polydispersity of particle size, showing the existence of a proper range of size dispersity for the formation of the Laves phase. The real-space analysis of the local environments of the particles revealed that the C14 phase can accommodate the particles with a broader range of interparticle distance and a less uniform local environment, such that the PDMS coronal blocks of the micelles with greater size dispersity suffered a lower degree of packing frustration when they organized into a C14 lattice. In view of the colloid-like nature of the micelle, a size fractionation process found in the crystallization of polydisperse colloidal particles was proposed as the mechanism for directing the effective development of C14 phase from the LLP phase. Due to the metastable nature of the ordered phases, their order–disorder transition temperatures were found to depend strongly on the structures of the LLP phases from which they developed and a strong memory effect underlying the phase transitions was identified.

Microstructure-Thermal Property Relationships of Poly (Ethylene Glycol-b-Caprolactone) Copolymers and Their Micelles.

The crystallinity of polymers strongly affects their properties. For block copolymers, whereby two crystallisable blocks are covalently tethered to one another, the molecular weight of the individual blocks and their relative weight fraction are important structural parameters that control their crystallisation. In the case of block copolymer micelles, these parameters can influence the crystallinity of the core, which has implications for drug encapsulation and release. Therefore, in this study, we aimed to determine how the microstructure of poly(ethylene glycol-b-caprolactone) (PEG-b-PCL) copolymers contributes to the crystallinity of their hydrophobic PCL micelle cores. Using a library of PEG-b-PCL copolymers with PEG number-average molecular weight (Mn) values of 2, 5, and 10 kDa and weight fractions of PCL (fPCL) ranging from 0.11 to 0.67, the thermal behaviour and morphology were studied in blends, bulk, and micelles using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WXRD), and Synchrotron wide-angle X-ray scattering (WAXS). Compared to PEG and PCL homopolymers, the block copolymers displayed reduced crystallinity in the bulk phase and the individual blocks had a large influence on the crystallisation of one another. The fPCL was determined to be the dominant contributor to the extent and order of crystallisation of the two blocks. When fPCL < 0.35, the initial crystallisation of PEG led to an amorphous PCL phase. At fPCL values between 0.35 and 0.65, PEG crystallisation was followed by PCL crystallisation, whereas this behaviour was reversed when fPCL > 0.65. For lyophilised PEG-b-PCL micelles, the crystallinity of the core increased with increasing fPCL, although the core was predominately amorphous for micelles with fPCL < 0.35. These findings contribute to understanding the relationships between copolymer microstructure and micelle core crystallinity that are important for the design and performance of micellar drug delivery systems, and the broader application of polymer micelles.

PS-b-P4VP block copolymer micelles as a soft template to grow openly porous nickel films for alkaline hydrogen evolution

Highly porous Ni films have been potentiostatically synthesised by micelle-assisted electrodeposition using custom-made PS-b-P4VP block copolymer micelles as a soft template. Two PS-b-P4VP block copolymers with PS/P4VP block ratios of 1:1 and 1:4 were used for the micelle-assisted electrodeposition, resulting in Ni films with large pores of diameters varying from 25 to 600 nm (1:1), and from 10 to 230 nm (1:4). As a result of the interconnected porosity, and hence the drastic increase of the surface-to-volume ratio, the electrocatalytic performance at hydrogen evolution reaction (HER) in alkaline media is significantly improved in comparison to a dense Ni film, and—more importantly—even in comparison to a highly mesoporous Ni film with monodisperse 10 nm wide pores. Most remarkably, it is discovered that the openly porous Ni electrocatalysts not only lead to a simple increase in HER current density, but also to a lower overpotential and a better long-term performance. While the bulk of the films is metallic, Ni(OH)2 is formed on the surfaces of all Ni films during HER. This effect leads to an initial decrease of the catalytic activity, but provides excellent stability in alkaline media. The presented synthesis process for pure Ni may be readily adopted to any other electroplatable metals and alloys.

Thermo-responsive PNIPAAm-b-PLA amphiphilic block copolymer micelle as nanoplatform for docetaxel drug release

Thermo-responsive PNIPAAm-b-PLA amphiphilic block copolymer micelle as nanoplatform for docetaxel drug release

Micellization: A new principle in the formation of biomolecular condensates.

Phase separation is a fundamental mechanism for compartmentalization in cells and leads to the formation of biomolecular condensates, generally containing various RNA molecules. RNAs are biomolecules that can serve as suitable scaffolds for biomolecular condensates and determine their forms and functions. Many studies have focused on biomolecular condensates formed by liquid-liquid phase separation (LLPS), one type of intracellular phase separation mechanism. We recently identified that paraspeckle nuclear bodies use an intracellular phase separation mechanism called micellization of block copolymers in their formation. The paraspeckles are scaffolded by NEAT1_2 long non-coding RNAs (lncRNAs) and their partner RNA-binding proteins (NEAT1_2 RNA-protein complexes [RNPs]). The NEAT1_2 RNPs act as block copolymers and the paraspeckles assemble through micellization. In LLPS, condensates grow without bound as long as components are available and typically have spherical shapes to minimize surface tension. In contrast, the size, shape, and internal morphology of the condensates are more strictly controlled in micellization. Here, we discuss the potential importance and future perspectives of micellization of block copolymers of RNPs in cells, including the construction of designer condensates with optimal internal organization, shape, and size according to design guidelines of block copolymers.

Aggregation-Induced Ignition of Near-Infrared Phosphorescence of Non-Symmetric [Pt(C^N*N'^C')] Complex in Poly(caprolactone)-based Block Copolymer Micelles: Evaluating the Alternative Design of Near-Infrared Oxygen Biosensors.

In the present work, we described the preparation and characterization of the micelles based on amphiphilic poly(ε-caprolactone-block-ethylene glycol) block copolymer (PCL-b-PEG) loaded with non-symmetric [Pt(C^N*N’^C’)] complex (Pt1) (where C^N*N’^C’: 6-(phenyl(6-(thiophene-2-yl)pyridin-2-yl)amino)-2-(tyophene-2-yl)nicotinate). The obtained nanospecies displayed the ignition of near-infrared (NIR) phosphorescence upon an increase in the content of the platinum complexes in the micelles, which acted as the major emission component at 12 wt.% of Pt1. Emergence of the NIR band at 780 nm was also accompanied by a 3-fold growth of the quantum yield and an increase in the two-photon absorption cross-section that reached the value of 450 GM. Both effects are believed to be the result of progressive platinum complex aggregation inside hydrophobic poly(caprolactone) cores of block copolymer micelles, which has been ascribed to aggregation induced emission (AIE). The resulting phosphorescent (Pt1@PCL-b-PEG) micelles demonstrated pronounced sensitivity towards molecular oxygen, the key intracellular bioanalyte. The detailed photophysical analysis of the AIE phenomena revealed that the NIR emission most probably occurred due to the excimeric excited state of the 3MMLCT character. Evaluation of the Pt1@PCL-b-PEG efficacy as a lifetime intracellular oxygen biosensor carried out in CHO-K1 live cells demonstrated the linear response of the probe emission lifetime towards this analyte accompanied by a pronounced influence of serum albumin on the lifetime response. Nevertheless, Pt1@PCL-b-PEG can serve as a semi-quantitative lifetime oxygen nanosensor. The key result of this study consists of the demonstration of an alternative approach for the preparation of NIR biosensors by taking advantage of in situ generation of NIR emission due to the nanoconfined aggregation of Pt (II) complexes inside the micellar nanocarriers.

Synthesis and Evaluation of Thermoresponsive Renewable Lipid-Based Block Copolymers for Drug Delivery.

Polymeric micelle forming from self-assembly of amphiphilic macromolecules is one of the most potent drug delivery systems. Fatty acids, naturally occurring hydrophobic lipid components, can be considered as potential candidates for the fabrication of block copolymer micelles. However, examples of synthesis of responsive block copolymers using renewable fatty acids are scarce. Herein, we report the synthesis, characterization and testing of block copolymer micelles composed of a renewable fatty-acid-based hydrophobic block and thermoresponsive hydrophilic block for controlled drug delivery. The block copolymers of functionalized fatty acid and poly(N-isopropylacrylamide) (PNIPAM) were prepared via consecutive microwave-assisted reversible addition fragmentation chain transfer (RAFT) polymerization. The block copolymers with variable hydrophobic block length self-assembled in aqueous media and formed spherical nanoparticles of ~30 nm with low critical micelle concentration (CMC). To demonstrate the proof-of-concept, carbamazepine (CBZ) was used as a hydrophobic model drug to evaluate the performance of these micelles as nanocarriers. The in vitro drug release tests were carried out below (25 °C) and above (37 °C) the lower critical solution temperature (LCST) of the block copolymer. The drug release showed obvious temperature-triggered response and an accelerated drug release at 37 °C.

Triblock copolymer micelle model of spherical paraspeckles.

Paraspeckles are nuclear bodies scaffolded by RNP complexes of NEAT1_2 RNA transcripts and multiple RNA-binding proteins. The assembly of paraspeckles is coupled with the transcription of NEAT1_2. Paraspeckles form the core-shell structure, where the two terminal regions of NEAT1_2 RNP complexes compose the shell of the paraspeckle and the middle regions of these complexes compose the core. We here construct a theoretical model of paraspeckles by taking into account the transcription of NEAT1_2 in an extension of the theory of block copolymer micelles. This theory predicts that the core-shell structure of a paraspeckle is assembled by the association of the middle region of NEAT1_2 RNP complexes due to the multivalent interactions between RBPs bound to these regions and by the relative affinity of the terminal regions of the complexes to the nucleoplasm. The latter affinity results in the effective repulsive interactions between terminal regions of the RNA complexes and limits the number of complexes composing the paraspeckle. In the wild type, the repulsive interaction between the middle and terminal block dominates the thermal fluctuation. However, the thermal fluctuation can be significant in a mutant, where a part of the terminal regions of NEAT1_2 is deleted, and distributes the shortened terminal regions randomly between the shell and the core, consistent with our recent experiments. With the upregulated transcription, the shortened terminal regions of NEAT1_2 in a deletion mutant is localized to the core to decrease the repulsive interaction between the terminal regions, while the structure does not change with the upregulation in the wild type. The robustness of the structure of paraspeckles in the wild type results from the polymeric nature of NEAT1_2 complexes.

Electrospinning of 1D Fiber‐Like Block Copolymer Micelles with a Crystalline Core

Electrospinning is a simple, low-cost, and high throughput technique that allows for the processing of polymers into fibers. The process can be controlled to allow access for well-defined continuous fibers that are of interest for a wide range of applications including as tissue scaffolds, as nanowires in optoelectronic devices, and in catalysis. Conventional electrospinning processes use polymer solutions with high molecular weights. Here, the electrospinning of 1D fiber-like block copolymer micelles containing a crystalline core is reported. The successfully accessed core-shell microfibers in which 1D micelles containing a crystalline poly(ferrocenyldimethylsilane) (PFS) core are immobilized on a polystyrene microfiber via coaxial electrospinning. Furthermore, efforts to extend this approach to the use of 1D micelles comprising of a crystalline, π-conjugated poly(di-n-hexylfluorene) (PDHF) core are described. Electrospinning is also successfully used to prepare microfibers consisting solely of 1D micelles with a PFS crystalline core, the first examples where a template material is not required.

Symmetry-Breaking Plasmonic Mesoporous Gold Nanoparticles with Large Pores

Creating free-standing gold nanoparticles (Au NPs) with large pores is desirable because the exterior and interior voids can enhance electrocatalytic activity, mass transport, and optical extinction properties. However, the high mobility and significant positive reduction potential of Au precursors make it challenging to create Au NPs with pores of sufficient size to strongly interact with light. We demonstrate a method to synthesize mesoporous Au NPs with large, tunable pores. l-Cysteine acts as a metallogelator to form a dense, less mobile Au(I)–thiolate precursor that traps aggregated block copolymer micelles and facilitates the reduction of mesoporous Au NPs. Electron tomography measurements showed that the pores were distributed throughout the interior and exterior of the particle. Electrochemical methods were used to estimate the chemical reactivity of the surface active sites and estimate the accessible surface area of the pores to ensure that the metal surfaces were maximally accessible to the environment. The 3D models generated by tomography were then used to simulate their optical properties. Mesoporous Au NPs support multipolar plasmon resonances that penetrate deep into the interior pores of the NP. A simple model indicates that porosity affects the local optical conductivity of the NP by subdividing it into tiny nanoscale junctions that redshift the plasmon modes without changing the overall size or shape of the NPs. Large pores promote symmetry breaking, causing the quadrupolar and dipolar modes to overlap and form strongly hybridized plasmon modes. In the context of photocatalysis, porosity-induced symmetry breaking is advantageous because strong electric fields of the plasmon are colocalized along concave/convex features where step-edges and kinks in the atomic structure generate numerous catalytic active sites. Plasmon-enhanced photodegradation of metanil yellow was used to demonstrate the superior photocatalytic properties of meso Au NPs versus nonporous Au NPs.

RGD Nanoarrays with Nanospacing Gradient Selectively Induce Orientation and Directed Migration of Endothelial and Smooth Muscle Cells.

Directed migration of cells through cell-surface interactions is a paramount prerequisite in biomaterial-induced tissue regeneration. However, whether and how the nanoscale spatial gradient of adhesion molecules on a material surface can induce directed migration of cells is not sufficiently known. Herein, we employed block copolymer micelle nanolithography to prepare gold nanoarrays with a nanospacing gradient, which were prepared by continuously changing the dipping velocity. Then, a self-assembly monolayer technique was applied to graft arginine-glycine-aspartate (RGD) peptides on the nanodots and poly(ethylene glycol) (PEG) on the glass background. Since RGD can trigger specific cell adhesion via conjugating with integrin (its receptor in the cell membrane) and PEG can resist protein adsorption and nonspecific cell adhesion, a nanopattern with cell-adhesion contrast and a gradient of RGD nanospacing was eventually prepared. In vitro cell behaviors were examined using endothelial cells (ECs) and smooth muscle cells (SMCs) as a demonstration. We found that SMCs exhibited significant orientation and directed migration along the nanospacing gradient, while ECs exhibited only a weak spontaneously anisotropic migration. The gradient response was also dependent upon the RGD nanospacing ranges, namely, the start and end nanospacings under a given distance and gradient. The different responses of these two cell types to the RGD nanospacing gradient provide new insights for designing cell-selective nanomaterials potentially used in cell screening, wound healing, etc.

Micellization, aggregation, and gelation of polystyrene-block-poly(ethylene oxide) in cosolvents added with hydrochloric acid

The micellization, aggregation, and gelation of the polystyrene-block-poly(ethylene oxide) block copolymer in solutions were quantitatively analyzed by small-angle X-ray scattering. The content and concentration of added hydrochloric acid influence the micellization, aggregation, and gelation of a polystyrene-block-poly(ethylene oxide) block copolymer in tetrahydrofuran/water and dimethylformamide/water cosolvents added with hydrochloric acid. The polystyrene-block-poly(ethylene oxide) block copolymer forms spherical micelles with screened Coulomb repulsions when dispersed in tetrahydrofuran/water cosolvents added with hydrochloric acid. The screened Coulomb repulsion arises from the poly(ethylene oxide) shells bound with protonated water and surrounded by unbalanced negative charges. If excessive water is introduced from hydrochloric acid, the non-solvent quality of tetrahydrofuran/water cosolvent predominantly causes aggregation of spherical micelles. Such screened Coulomb repulsions do not form for core-shell cylinders dispersed in dimethylformamide/water added with hydrochloric acid. Hydrochloric acid tends to form complexes with dimethylformamide. The length of core-shell cylinders can increase with the increased content of hydrochloric acid. Long core-shell cylinders favorably form three-dimensional networks through inter-cylinder entanglement. Furthermore, the absence of screened Coulomb repulsions makes entangled cylinders more compact to strongly trap the liquid phase. Thus, gels occurred in dimethylformamide/water cosolvents with added hydrochloric acid. Nevertheless, the content of added hydrochloric acid should be finely controlled. Adding a large amount of hydrochloric acid prohibits network formation and instead favors kinetically trapped rigid cylinders. This study has demonstrated that finely controlling solvent quality by additives provides a physical design strategy for fabricating cylindrical micelles with tunable properties in solutions. This should offer the fundamental understanding of self-assembly for potential applications of block copolymer micelles.

A meticulous study on the interaction of bile salts with star block copolymeric micelles

Here we report, the interaction of a star block copolymer T1304 and biologically important additive, bile salts (BS) in aqueous condition. Bile salts used for the system are sodium cholate (NaC), sodium taurocholate (NaTC) and sodium deoxycholate (NaDC). Mixed micelles of T1304-BS have been assessed by employing cloud point (CP), scattering [dynamic light scattering (DLS), small-angle neutron scattering (SANS)] and spectral techniques [UV–visible, 1H NMR, and fluorescence spectroscopy]. As the system is comprising of two important bio amphiphiles, so the solubilization of drug Quercetin (QCT) in this mixed micellar environment is also studied to give it a broader spectrum. An increased trend in CP along with a decrease of micellar size is observed with the addition of BSs. With increasing concentration of bile salts, the mixed micellar aggregates are becoming surfactant rich and maximum replacement of T1304 molecule is done by NaDC due to its lower CMC and more hydrophobicity.

Intracellular K+-Responsive Block Copolymer Micelles for Targeted Drug Delivery of Curcumin.

Curcumin (CUR) is a natural bioactive compound that has attracted attention as a “golden molecule” due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K+-responsive controlled-release properties is designed and developed. The polymeric micelles are self-assembled by poly (N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5-co-N, N-dimethylacrylamide)-b-DSPE (PNDB-b-DSPE) block copolymers, and CUR. CUR is successfully loaded into the micelles with a CUR loading content of 6.26 wt%. The proposed CUR-PNDB-DSPE polymeric micelles exhibit a significant CUR release in simulated intracellular fluid due to the formation of 2 : 1 ‘‘sandwich’’ host–guest complexes of 15-crown-5 and K+, which lead to the hydrophilic outer shell of micelles to collapse and the drug to rapidly migrate out of the micelles. In vitro, the B16F10 cell experiment indicates that CUR-PNDB-DSPE micelles exhibit a high cellular uptake and excellent intracellular drug release in response to the intracellular K+ concentration. Moreover, CUR-PNDB-DSPE micelles show high cytotoxicity to B16F10 cells compared to free CUR and CUR-PEG-DSPE micelles. The polymeric micelles with intracellular K+-responsive controlled release properties proposed in this study provide a new strategy for designing novel targeted drug delivery systems for CUR delivery for cancer treatment.

Biophysical Characterization of Interactions between Serum Albumin and Block Copolymer Micelles.

Block copolymer micelles have demonstrated great promise in the solubilization of hydrophobic drugs, but an understanding of the blood stability of the drug-laden micelles is needed for therapeutic advancement of micelle technologies. Following intravenous administration, mPEG-CL and mPEG-LA micelles have demonstrated quick release of their cargo and disassembly in blood, but the prevailing mechanisms of micelle disruption and key biomacromolecules driving this disruption have yet to be elucidated. Although protein interactions with solid polymeric nanoparticles have been characterized, not much is known regarding protein interactions with dynamic block copolymer micelles. Herein, we characterize the interaction of bovine and human serum albumins (BSA and HSA) with polymeric micelles, mPEG-CL and mPEG-LA, using protein fluorescence, isothermal titration calorimetry (ITC), and circular dichroism (CD) spectroscopy. We find that BSA and HSA have interactions with mPEG-CL, while only HSA is observed to weakly interact with mPEG-LA. Protein fluorescence suggests that binding of HSA to mPEG-CL and mPEG-LA is driven by electrostatic interactions. ITC suggests an interaction between serum albumin and mPEG-CL block copolymers driven by hydrogen bonding and electrostatic interactions in physiological MOPS-buffered saline, while mPEG-LA has no measurable interaction with either of the serum albumins. CD spectroscopy demonstrates that the protein secondary structure is intact in both proteins in the presence of mPEG-CL and mPEG-LA. Overall, BSA is not always predictive of polymeric interactions with HSA. Understanding of interactions between serum proteins and block copolymer micelles and the exact mechanisms of destabilization will direct the rational design of block copolymer systems for improving blood stability.

Block Co-PolyMOC Micelles and Structural Synergy as Composite Nanocarriers.

Conventional micelles of amphiphilic block copolymers (BCPs) disassemble into individual polymer chains upon dilution to a critical concentration, which causes the premature release of the encapsulated drugs and reduces the drug's bioavailability. Here, by integrating the emerging metal-organic cage (MOC) materials with BCPs, we introduce a new type of composite micellar nanoparticles, block co-polyMOC micelles (or BCPMMs), that are self-assembled in essence yet remarkably stable against dilution. BCPMMs are fabricated via a stepwise assembly strategy that combines MOCs and BCPs in a well-defined, unimolecular core-shell structure. The synergistical interplay between the two components accounts for the particle stability: the MOC core holds BCPs firmly in place and the BCPs increase the MOC's bioavailability. When used as nanocarriers for anticancer drugs, BCPMMs showed an extended blood circulation, a favorable biodistribution, and eventually an improved treatment efficacy in vivo. Given the versatility in designing MOCs and BCPs, we envision that BCPMMs can serve as a modular platform for robust, multifunctional, and tunable nanomedicine.

Stimuli-responsive vitamin E-based micelles: Effective drug carriers with a controlled anticancer drug release

Herein, a series of vitamin E-based TPGS-poly(2-(dimethylamino)ethyl methacrylate)- b -poly(3-vinyl benzaldehyde) block copolymer micelles were synthesized via reversible addition−fragmentation chain-transfer polymerization (RAFT). d -α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) is a good candidate to overcome the big problem of multidrug resistance in cancer therapy because TPGS can inhibit permeability of glycoprotein (P-gp) resulting in restored sensitivity to chemotherapeutics. Doxorubicin (DOX) was loaded within the micelles, as an anticancer model drug, via hydrolytic amide linkage in the hydrophobic block. The DOX-loaded micelles demonstrated high potential as anticancer drug delivery systems through the release of the drug under acidic conditions, varying from pH 7.4 to 5.0. Three different micelles compositions were investigated with various ratios of hydrophilic and hydrophobic blocks (1:1, 4:3, and 4:1). The DOX-conjugated polymer with the shortest hydrophobic segment (4:1), TPGS-poly(2-(dimethylamino)ethyl methacrylate) 125 - b -poly(3-vinyl benzaldehyde) 91 , demonstrated excellent in vitro cytotoxicity with pH-responsive characteristics in comparison to free DOX. Although the higher degree of polymerization of the hydrophobic block promoted the drug loading efficiency of the micelles these compositions demonstrated lower cytotoxicity to the A549 cell line of human lung adenocarcinoma. It was concluded that the prepared pH-responsive micelles based on TPGS are promising drug carriers for anticancer drug delivery systems and could be considered to provide multi-drug resistance cancer treatments after further in vitro biological studies. • A series of block copolymers containing vitamin E moieties were synthesized. • Micelles with hydrophobic core and hydrophilic shell were loaded with DOX. • In vitro loading and release studies of DOX were performed. • Biocompatibility of vitamin E based micelles on healthy human cells was shown. • Obtained pH-responsive micelles appeared to be promising drug carriers.

Polynorbornene-derived block copolymer micelles via ring‐opening metathesis polymerization with capacity of hydrogen sulfide generation

Hydrogen sulfide (H2S), a gasotransmitter, has recently attracted significant attention for its therapeutic properties. In order to achieve controlled H2S release, polymer-based H2S donors are essential. In this report, we constructed amphiphilic block copolymer (PNEG-b-PNSATO) consisting of norbornene-mPEG (Nor-mPEG) as a hydrophilic part and norbornene-conjugated SATO moiety (Nor-SATO) as a hydrophobic part via ring-opening metathesis polymerization (ROMP). Different SATO donor contents were tested with different hydrophilic/hydrophobic polymer ratios in order to find the ideal block copolymer to release H2S, for example, PNEG8k-b-PNSATO4k, PNEG8k-b-PNSATO8k, PNEG8k-b-PNSATO12k. The block copolymers could form micelles with a range of sizes from 41 to 57 nm. The PNEG-b-PNSATO polymeric micelles release H2S at a prolonged release rate (peak time of 60–70 min). PNEG-b-PNSATO polymeric micelles were assessed by MTT assay against L929 cells, showing excellent biocompatibility. Fluorescent imaging was used to gauge H2S release. Additionally, the PNEG-b-PNSATO polymeric micelles were demonstrated to protect against oxidative damage induced by a lethal dose of H2O2, demonstrating the possibility of using this system to achieve H2S therapeutic effects.