Core–corona inversion of micelles of diblock copolymer poly(acrylic acid)‐block‐poly(N‐isopropylacrylamide) (PAA‐b‐PNIPAM), has been successfully realized by switching either pH or temperature. The strong interaction of doxorubicin with the PAA block and the pH‐sensitive drug release from the polymer make the system very useful as a controlled drug delivery system. The encapsulation of hydrophobic Nile Red molecules above the lower critical solution temperature of PNIPAM suggests that this polymer may be useful for removing hydrophobic pollutants.
Here, the cylinder to sphere transition property is reported in kinetically trapped block copolymer (BCP) nano‐objects made from polystyrene‐block‐poly(N‐isopropylacrylamide) (PS‐b‐PNIPAM) in ethanol. The PS‐b‐PNIPAM BCPs are found to self‐assemble into hexagonally packed cylindrical morphology in bulk. When dispersing the bulk microphase‐separated BCP materials in selective solvent, nanocylinders stabilized by kinetically trapped PS cores were obtained. However, when the kinetic barrier is removed by external energy input, a morphology transition from cylinder to sphere occurred. The transition procedure could be accelerated by applying higher external energy, which could be realized by using higher temperatures as well as treating with ultrasonic. Additionally, lowering the kinetic barrier by using polymers with a shorter PS block also accelerates the morphology transition process.
Herein the synthesis of core cross‐linked (CCL) mixed micelles through a UV‐promoted thiol–ene addition onto lipid core unsaturations and the subsequent release of an encapsulated drug depending on the external conditions (pH/temperature) are reported. The thiol–ene addition proceeds even in the absence of a photoinitiator to reach a complete conversion in a few minutes in bulk. The cross‐linking reaction is applied in aqueous media onto lipid‐b‐poly(acrylic acid) (lipid‐b‐PAA) only and then a mixture of pH‐sensitive lipid‐b‐PAA and thermo‐sensitive lipid‐block‐poly(2‐isopropyl‐2‐oxazoline) copolymers. Structurally CCL micelles, preserved in any conditions, with a stimuli‐sensitive corona whose swelling depends on the external pH or/and temperature, are successfully prepared. The release of vitamin K1 (VK1) is then investigated from all the previous systems and demonstrates a strong dependency to the external conditions. Indeed, the dual‐sensitive CCL micelles release VK1 only when two triggers (pH 10 and T = 38 °C) are simultaneously activated.
A convenient one‐pot method for the controlled synthesis of polystyrene‐block‐polycaprolactone (PS‐b‐PCL) copolymers by simultaneous reversible addition–fragmentation chain transfer (RAFT) and ring‐opening polymerization (ROP) processes is reported. The strategy involves the use of 2‐(benzylsulfanylthiocarbonylsulfanyl)ethanol (1) for the dual roles of chain transfer agent (CTA) in the RAFT polymerization of styrene and co‐initiator in the ROP of ε‐caprolactone. One‐pot polymerizations using the electrochemically stable ROP catalyst diphenyl phosphate (DPP) yield well‐defined PS‐b‐PCL in a relatively short reaction time (≈4 h; = 9600?43 600 g mol?1; / = 1.21?1.57). Because the hydroxyl group is strategically located on the Z substituent of the CTA, segments of these diblock copolymers are connected through a trithiocarbonate group, thus offering an easy way for subsequent growth of a third segment between PS and PCL. In contrast, an oxidatively unstable Sn(Oct)2 ROP catalyst reacts with (1) leading to multimodal distributions of polymer chains with variable composition.
The combination of stimuli‐responsive polymers and proteins that can transport drugs is a promising approach for drug delivery. The formation of ferritin–poly(2‐dimethylaminoethyl methacrylate) (PDMAEMA) conjugates by atom‐transfer radical polymerization from the protein macroinitiator is described. PDMAEMA is a dual‐stimuli‐responsive polymer and the thermo‐ and pH‐responsive properties of the resulting conjugates are studied in detail with dynamic light scattering (DLS). Additionally, it is demonstrated that the lower critical solution temperature (LCST) of the protein–polymer conjugates can be further adjusted by the ionic strength of the solution. The conjugates are also characterized by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), matrix‐assisted laser desorption ionization‐time of flight (MALDI‐ToF) mass spectrometry, and NMR spectroscopy. The obtained MALDI‐ToF mass spectra are exceptional for protein–polymer conjugates and have not been so often reported.
Reduction‐responsive biodegradable polymeric micelles based on functional 2‐methylene‐1,3‐dioxepane (MDO) copolymers are developed and investigated for triggered doxorubicin (DOX) release. The MDO‐based copolymers P(MDO‐co‐PEGMA‐co‐PDSMA) are synthesized via the simple one‐step radical ring‐opening copolymerization of MDO, poly(ethylene glycol) methyl ether methacrylate (PEGMA), and pyridyldisulfide ethylmethacrylate (PDSMA). The copolymers can self‐assemble to form micelles in aqueous solution. DOX, a model anticancer drug, is loaded into the micelles with the drug loading content (DLC) of 11.3%. The micelles can be disassembled under a reductive environment (10 × 10?3m glutathione), which results in a triggered drug release behavior. The glutathione‐mediated intracellular drug release of DOX‐loaded micelles is investigated against A549 cells. Confocal laser scanning microscopy (CLSM) results demonstrated that DOX‐loaded micelles exhibits faster drug release in glutathione monoester (GSH‐OEt)‐pretreated A549 cells, compared with untreated and buthionine sulfoximine (BSO)‐pretreated A549 cells. Based on the facile synthetic strategy, the reduction‐sensitive biodegradable micelles with triggered intracellular drug release are promising for anticancer drug delivery.
The incorporation of Au nanoparticles to polystyrene‐b‐quaternized poly(2‐vinylpyridine) (SQVP) micelles and their interaction with DNA in aqueous solutions is investigated. Micelles of a well‐defined single population in solution keep their size while AuNPs appear to bind near their core, as observed by static and dynamic light scattering. The apparent molecular weight increases as a function of Au concentration, which proves controllable NP loading. Au‐loaded SQVP micelles create complexes with DNA where the micelles still preserve their morphology and size. The fluorescence intensity from SQVP‐Au aggregates drops as Au accumulates on the micelles. The fluorescence spectrum remains practically unaffected by the addition of DNA. SQVP micelles offer a stable and well‐defined template for the formulation of drug and DNA nanocarriers as hierarchically self‐assembled hybrid nanostructured functional materials.
Redox and pH dual‐responsive supramolecular micelles are prepared through a traditional polymer block and a supramolecular block to completely release the drugs. Ferrocene‐introduced and hydrophobic‐modified β‐cyclodextrin (β‐CD‐Fc‐Ace, where β‐CD, Fc, and Ace refer to β‐cyclodextrin, ferrocene, and acetal, respectively) is used to build the supramolecular block. Adamantane‐terminated poly(ethylene glycol) methyl ether (mPEG‐Ada) is the traditional polymer block. The average diameter of supramolecular micelles is ≈100 nm. Supramolecular micelles are able to control the release of the drugs in the cancer cells due to pH and redox microenvironments.
Well‐defined magnetic polyelectrolytes with tetrachlorideferrate (FeCl4?) as counter ion are prepared. In this approach, norbornene‐based monomer containing ammonium chloride group (TAENDI‐Cl) is designed and synthesized. Well‐defined magnetic polymers (Poly(TAENDI‐FeCl4)) are obtained by ring‐opening metathesis polymerization of TAENDI‐Cl in the presence of Grubbs third generation catalyst followed by complexing with FeCl3. Magnetic block copolymers are thus prepared. Both the monomer and polymers are paramagnetic as measured by superconducting quantum interference device method. Studies show that the magnetic susceptibility increases with increasing degree of polymerization (DP) and reaches maximum at DP of 100, and then decreases with increasing DP. Block copolymer with lower FeCl4? content shows higher magnetic susceptibility. And, by introducing FeCl4?, the polymers show obviously magnetic responsive in solution, powder, and film which have potential applications in magnetic switching, transport, and separation.
Amphiphilic triblock copolymers with poly(2‐methyl‐2‐oxazoline) (MeOx) end blocks and a poly(2‐n‐butyl‐2‐oxazoline) (nBuOx) middle block have been found to solubilize large amounts of the cancer drug paclitaxel (PTX) whereas this is not the case when the middle block is more hydrophobic, such as poly(2‐n‐nonyl‐2‐oxazoline) (NOx) (Schulz et al., ACS Nano 2014 , 8, 2686). To further elucidate the origin of this behavior, dilute aqueous solutions (5–10 mg mL?1) of these two copolymers have been investigated by small‐angle neutron scattering (SANS), both in the absence and presence of PTX. Whereas PMeOx‐b‐PNOx‐b‐PMeOx forms mainly worm‐like micelles coexisting with large aggregates, spherical micelles are predominant in PMeOx‐b‐PnBuOx‐b‐PMeOx. Already small PTX concentrations lead to shape changes in PMeOx‐b‐PNOx‐b‐PMeOx toward spherical micelles. In contrast, changes in the aggregation behavior of PMeOx‐b‐PnBuOx‐b‐PMeOx are only observed at higher PTX concentrations with a transformation into raspberry‐like particles, which may explain the high PTX loading capacity of PMeOx‐b‐PnBuOx‐b‐PMeOx micelles.
The successful postfunctionalization of multiarm star polystyrene (PS) with pentafluorophenyl and allyl moieties at the periphery is demonstrated employing modular thiol‐para‐fluoro and photoinduced radical thiol‐ene double “click” reactions, respectively. α‐Fluoro and α‐allyl functionalized PS (α‐fluoro‐PS and α‐allyl‐PS) are in situ prepared by atom transfer radical polymerization of styrene and their mixture is used as macroinitiator in a crosslinking reaction with divinyl benzene (DVB) yielding (fluoro‐PS)m–polyDVB–(allyl‐PS)m multiarm star polymer. It is found that the multiarm star polymer includes nearly identical number of arms possessing pentafluorophenyl and allyl moieties at the periphery. The obtained multiarm star polymer is then reacted with 1‐propanethiol through thiol‐para‐fluoro “click” reaction to give (propyl‐PS)m–polyDVB–(allyl‐PS)m multiarm star polymer, which is subsequently reacted with N‐acetyl‐l ‐cysteine methyl ester via radical thiol‐ene “click” reaction in order to give well‐defined heterofunctionalized (propyl‐PS)m–polyDVB–(cysteine‐PS)m multiarm star polymer, with higher molecular weight and narrow molecular weight distribution. Multiarm star polymers are characterized by using viscotek triple detection gel permeation chromatography, 1H, and 19F NMR.
Narrowly distributed (N‐isopropylacrylamide) (NIPAM) polymers are prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. After successful cleavage of the trithiocarbonate end groups (thiol generation), they can be grafted to styrene‐butadiene rubber (SBR) by a radical thiol‐ene reaction leading to various grafted SBR‐copolymers. During the grafting reaction, no crosslinking or branching of the SBR can be observed. Measurements of the contact angle of water show that the lower critical solution temperature (LCST) properties of the PNIPAM fraction affect the SBR. Films of the graft‐copolymer exhibit a distinct hydrophilicity below the LCST, while they show hydrophobic behavior above the LCST. Rheological measurements reveal a physical crosslinking of the functionalized SBR due to nanophase separation of the PNIPAM chains (hard phase) in the unpolar SBR. Compared with blends of SBR and PNIPAM, the PNIPAM‐grafted SBR possesses a much finer distribution of the PNIPAM domains (10–30 nm) within the matrix. In addition, two novel difunctional chain‐transfer agents are used, leading to difunctional PNIPAM, enabling a covalent crosslinking of SBR.
Poly(methyl methacrylate)‐block‐poly(4‐vinylpyridine), polystyrene‐block‐poly(4‐vinyl pyridine), and poly(ethylene glycol)‐block‐poly(4‐vinylpyridine) block copolymers are synthesized by successive atom transfer radical polymerization (ATRP), single‐electron‐transfer nitroxide‐radical‐coupling (SET‐NRC) and nitroxide‐mediated polymerization (NMP). This paper demonstrates that this new approach offers an efficient method for the preparation of 4‐vinylpyridine‐containing copolymers.
Thermoresponsive polypeptoids are promising candidates for medical applications due to their biomimetic properties. When such polymers are grafted on magnetic nanoparticles, materials can be obtained that combine a temperature‐triggered solubility transition with magnetic extraction. The synthesis of monodisperse, superparamagnetic iron oxide nanoparticles is described with densely surface‐grafted polypeptoid shells that have tunable thermoresponsive colloidal stability. The synthesis combines ligand exchange with controlled surface‐initiated polymerization of N‐substituted N‐carboxyanhydrides for the preparation of well‐defined core–shell nanoparticles.
Histidine–zinc interactions are believed to play a key role in the self‐healing behavior of mussel byssal threads due to their reversible character. Taking this as inspiration, the authors synthesize here histidine‐rich copolymers, as well as model histidine compounds and characterize them using isothermal titration calorimetry (ITC). With this approach, the influence of two different zinc(II) salts and the role in the complex formation of the amine function of the imidazole ring are investigated in detail. The extracted metal–ligand ratios are utilized to design novel self‐healing metallopolymers. For this purpose, n‐lauryl methacrylate is copolymerized with the histidine monomer via reversible addition‐fragmentation chain transfer polymerization. The copolymers are crosslinked using different zinc salts, and the resulting coatings are characterized with Raman spectroscopy to investigate the metal coordination behavior and with scratch healing tests to investigate the self‐healing capacity. Finally, the self‐healing behavior of the different materials is correlated with the metal–ligand binding affinity measured by ITC.
A series of highly branched star‐comb poly(ε‐caprolactone)‐block‐poly(l ‐lactide) (scPCL‐b‐PLLA) are successfully achieved using star‐shaped hydroxylated polybutadiene as the macroinitiator by a simple “grafting from” strategy. The ration of each segment can be controlled by the feed ratio of comonomers. These star‐comb double crystalline copolymers are well‐defined and expected to illustrate the influences of the polymer chain topology by comparing with their counterparts in linear‐shaped, star‐shaped, and linear‐comb shape. The crystallization behaviors of PCL‐b‐PLLA copolymers with different architectures are investigated systematically by means of wide‐angle X‐ray diffraction, differential scanning calorimetry, and polarized optical microscopy analysis. It is shown that the comb branched architectures promote the crystallization behavior of each constituent significantly. Both crystallinity and melting temperature greatly raise from linear to comb‐shaped copolymers. Compared to linear‐comb topology, the star‐comb shape presents some steric hindrance of the graft points, which decrease the crystallinity of scPCL‐b‐PLLA. Effects of copolymer composition and chain topology on the crystallization are studied and discussed.
Copolymerization of carbon dioxide (CO2) and propylene oxide (PO) is employed to generate amphiphilic polycarbonate block copolymers with a hydrophilic poly(ethylene glycol) (PEG) block and a nonpolar poly(propylene carbonate) (PPC) block. A series of poly(propylene carbonate) (PPC) di‐ and triblock copolymers, PPC‐b‐PEG and PPC‐b‐PEG‐b‐PPC, respectively, with narrow molecular weight distributions (PDIs in the range of 1.05–1.12) and tailored molecular weights (1500–4500 g mol?1) is synthesized via an alternating CO2/propylene oxide copolymerization, using PEG or mPEG as an initiator. Critical micelle concentrations (CMCs) are determined, ranging from 3 to 30 mg L?1. Non‐ionic poly(propylene carbonate)‐based surfactants represent an alternative to established surfactants based on polyether structures.
Reversibly light‐responsive micelles are constructed from an amphiphilic azobenzene‐containing diblock copolymer AZO‐mPEG‐poly(5)25. The copolymer is synthesized via ring‐opening polymerization of O‐carboxyanhydrides bearing alkyne group, followed by azide–alkyne click chemistry with an azide‐containing azobenzene derivative. AZO‐mPEG‐poly(5)25 can self‐assemble to spherical micelles. Light response of the polymeric micelles is demonstrated by UV–vis spectroscopy and scanning electron microscopy (SEM). SEM images show that after UV irradiation, the micelles are partly dissociated, which is ascribed to swelling of the hydrophobic chain because of hydrophobicity change during the trans–cis isomerization of the azobenzene group. After subsequent visible‐light irradiation, the morphology returns back to micelles.
Novel dual‐functional PEI‐poly(γ‐cholesterol‐l ‐glutamate) (PEI‐PCHLG) copolymers are developed for the first time. A series of PEI‐PCHLG (PEI‐1, PEI‐2, PEI‐3, and PEI‐4) with various PEI percentages and molecular weights are successfully synthesized, among which the poor organic solvent solubility of PEI‐1 precludes its further application. The other three copolymers can spontaneously self‐assemble into micelles; the critical micelle concentration (CMC) values are 0.66, 1.3, and 0.95 μmol L?1, respectively. PEI‐2 and PEI‐4, with lower CMC, are worth being further developed as promising drug carriers because of their resistance to dilution in circulation after systemic administration. However, PEI‐4 can form smaller‐sized micelles than PEI‐2 and has similar in vitro cytotoxicity to PEI. Thus, PEI‐4 is further investigated. PEI‐4 micelles can not only incorporate docetaxel (DTX) with high encapsulation efficiency (91.0%) and drug loading (4.3%), but also load pDNA efficiently at a ratio of 8:1 (w/w). DTX‐loaded PEI‐4 micelles (DTX‐PEI‐4) can also carry genes with the same gene‐binding capacity as PEI‐4 micelles. The above three micelles (DTX‐PEI‐4, pDNA‐PEI‐4, and pDNA/DTX‐PEI‐4) are sub‐micrometer‐sized and spherical. The results indicate that PEI‐4 containing 28.9% PEI, one of the PEI‐PCHLG copolymers, is a potential carrier for gene delivery, drug delivery, or even drug/gene co‐delivery.
In this paper, novel light‐responsive polyhedral oligomeric silsesquioxane (POSS) end‐capped poly(o‐nitrobenzyl methacrylate) (POSS–PNBMA) are synthesized by the combination of atom transfer radical polymerization (ATRP) and click chemistry. After subsequent partial photocleavage of PNBMA yielding poly(methacrylic acid) (PMAA), pH‐ and light‐responsive random copolymer of POSS–P(NBMA‐co‐MAA) is obtained. The o‐nitrobenzyl‐based amphiphilic hybrid polymer can self‐assemble into spherical micelles in aqueous solution. Hydrophobic POSS and PNBMA segments aggregate into the inner core, and the hydrophilic PMAA chains tend to stretch from the core. The micellar morphology can be tuned by pH changes and UV irradiation. Light irradiation leads to the transformation of P(NBMA‐co‐MAA) into PMAA and to the reorganization of the assemblies, causing the release of encapsulated guest molecule Nile Red into water. This dual‐responsive polymer has a broad potential use in targeted drug delivery.
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