Polymerization-induced self-assembly and disassembly during the synthesis of thermoresponsive ABC triblock copolymer nano-objects in aqueous solution

Polymerization-induced self-assembly (PISA) has been widely utilized as a powerful methodology for the preparation of various self-assembled AB diblock copolymer nano-objects in aqueous media. Moreover, it is well-documented that chain extension of AB diblock copolymer vesicles using a range of hydrophobic monomers via seeded RAFT aqueous emulsion polymerization produces framboidal ABC triblock copolymer vesicles with adjustable surface roughness owing to microphase separation between the two enthalpically incompatible hydrophobic blocks located within their membranes. However, the utilization of hydrophilic monomers for the chain extension of linear diblock copolymer vesicles has yet to be thoroughly explored; this omission is addressed for aqueous PISA formulations in the present study. Herein poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (G-H) vesicles were used as seeds for the RAFT aqueous dispersion polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Interestingly, this led to polymerization-induced disassembly (PIDA), with the initial precursor vesicles being converted into lower-order worms or spheres depending on the target mean degree of polymerization (DP) for the corona-forming POEGMA block. Moreover, construction of a pseudo-phase diagram revealed an unexpected copolymer concentration dependence for this PIDA formulation. Previously, we reported that PHPMA-based diblock copolymer nano-objects only exhibit thermoresponsive behavior over a relatively narrow range of compositions and DPs (see Warren et al., Macromolecules, 2018, 51, 8357–8371). However, introduction of the POEGMA coronal block produced thermoresponsive ABC triblock nano-objects even when the precursor G-H diblock copolymer vesicles proved to be thermally unresponsive. Thus, this new approach is expected to enable the rational design of new nano-objects with tunable composition, copolymer architectures and stimulus-responsive behavior.

Chain extension of linear AB diblock copolymer vesicles by seeded RAFT aqueous dispersion polymerization using a hydrophilic monomer C leads to polymerization-induced disassembly to form lower-order thermoresponsive ABC triblock copolymer nano-objects.     

Shape-shifting thermoreversible diblock copolymer nano-objects via RAFT aqueous dispersion polymerization of 4-hydroxybutyl acrylate

2-Hydroxypropyl methacrylate (HPMA) is a useful model monomer for understanding aqueous dispersion polymerization. 4-Hydroxybutyl acrylate (HBA) is an isomer of HPMA: it has appreciably higher aqueous solubility so its homopolymer is more weakly hydrophobic. Moreover, PHBA possesses a significantly lower glass transition temperature than PHPMA, which ensures greater chain mobility. The reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of HBA using a poly(ethylene glycol) (PEG₁₁₃) precursor at 30 °C produces PEG₁₁₃–PHBA_200–700 diblock copolymer nano-objects. Using glutaraldehyde to crosslink the PHBA chains allows TEM studies, which reveal the formation of spheres, worms or vesicles under appropriate conditions. Interestingly, the partially hydrated highly mobile PHBA block enabled linear PEG₁₁₃–PHBA_x spheres, worms or vesicles to be reconstituted from freeze-dried powders on addition of water at 20 °C. Moreover, variable temperature ¹H NMR studies indicated that the apparent degree of hydration of the PHBA block increases from 5% to 80% on heating from 0 °C to 60 °C indicating uniform plasticization. In contrast, the PHPMA_x chains within PEG₁₁₃–PHPMA_x nano-objects become dehydrated on raising the temperature: this qualitative difference is highly counter-intuitive given that PHBA and PHPMA are isomers. The greater (partial) hydration of the PHBA block at higher temperature drives the morphological evolution of PEG₁₁₃–PHBA₂₆₀ spheres to form worms or vesicles, as judged by oscillatory rheology, dynamic light scattering, small-angle X-ray scattering and TEM studies. Finally, a variable temperature phase diagram is constructed for 15% w/w aqueous dispersions of eight PEG₁₁₃–PHBA_200–700 diblock copolymers. Notably, PEG₁₁₃–PHBA₃₅₀ can switch reversibly from spheres to worms to vesicles to lamellae during a thermal cycle.

RAFT aqueous dispersion polymerization of 4-hydroxybutyl acrylate (HBA) affords shape-shifting thermoresponsive diblock copolymer nano-objects. ¹H NMR studies suggest that such behavior involves uniform plasticization of the PHBA block.     

Tuning the properties of hydrogen-bonded block copolymer worm gels prepared via polymerization-induced self-assembly

Polymerization-induced self-assembly (PISA) is exploited to design hydrogen-bonded poly(stearyl methacrylate)-poly(benzyl methacrylate) [PSMA-PBzMA] worm gels in n-dodecane. Using a carboxylic acid-based RAFT agent facilitates hydrogen bonding between neighboring worms to produce much stronger physical gels than those prepared using the analogous methyl ester-based RAFT agent. Moreover, tuning the proportion of these two types of end-groups on the PSMA chains enables the storage modulus (G′) of a 20% w/w worm gel to be tuned from ∼4.5 kPa up to ∼114 kPa. This is achieved via two complementary routes: (i) an in situ approach using binary mixtures of acid- and ester-capped PSMA stabilizer chains during PISA or (ii) a post-polymerization processing strategy using a thermally-induced worm-to-sphere transition to mix acid- and ester-functionalized spheres at 110 °C that fuse to form worms on cooling to 20 °C. SAXS and rheology studies of these hydrogen-bonded worm gels provide detailed insights into their inter-worm interactions and physical behavior, respectively. In the case of the carboxylic acid-functionalized worms, SAXS provides direct evidence for additional inter-worm interactions, while rheological studies confirm both a significant reduction in critical gelation concentration (from approximately 10% w/w to 2–3% w/w) and a substantial increase in critical gelation temperature (from 41 °C to 92 °C). It is remarkable that a rather subtle change in the chemical structure results in such improvements in gel strength, gelation efficiency and gel cohesion.

Carboxylic acid-capped diblock copolymer worms are prepared in n-dodecane via polymerization-induced self-assembly. Varying the proportion of terminal carboxylic acid groups modulates the inter-worm H-bonding interactions and hence the gel modulus.     

SAXS studies of the thermally-induced fusion of diblock copolymer spheres: formation of hybrid nanoparticles of intermediate size and shape

Dilute dispersions of poly(lauryl methacrylate)–poly(benzyl methacrylate) (PLMA–PBzMA) diblock copolymer spheres (a.k.a. micelles) of differing mean particle diameter were mixed and thermally annealed at 150 °C to produce spherical nanoparticles of intermediate size. The two initial dispersions were prepared via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate in n-dodecane at 90 °C. Systematic variation of the mean degree of polymerization of the core-forming PBzMA block enabled control over the mean particle diameter: small-angle X-ray scattering (SAXS) analysis indicated that PLMA₃₉–PBzMA₉₇ and PLMA₃₉–PBzMA₂₉₄ formed well-defined, non-interacting spheres at 25 °C with core diameters of 21 ± 2 nm and 48 ± 5 nm, respectively. When heated separately, both types of nanoparticles regained their original dimensions during a 25–150–25 °C thermal cycle. However, the cores of the smaller nanoparticles became appreciably solvated when annealed at 150 °C, whereas the larger nanoparticles remained virtually non-solvated at this temperature. Moreover, heating caused a significant reduction in mean aggregation number for the PLMA₃₉–PBzMA₉₇ nanoparticles, suggesting their partial dissociation at 150 °C. Binary mixtures of PLMA₃₉–PBzMA₉₇ and PLMA₃₉–PBzMA₂₉₄ nanoparticles were then studied over a wide range of compositions. For example, annealing a 1.0% w/w equivolume binary mixture led to the formation of a single population of spheres of intermediate mean diameter (36 ± 4 nm). Thus we hypothesize that the individual PLMA₃₉–PBzMA₉₇ chains interact with the larger PLMA₃₉–PBzMA₂₉₄ nanoparticles to form the hybrid nanoparticles. Time-resolved SAXS studies confirm that the evolution in copolymer morphology occurs on relatively short time scales (within 20 min at 150 °C) and involves weakly anisotropic intermediate species. Moreover, weakly anisotropic nanoparticles can be obtained as a final copolymer morphology over a restricted range of compositions (e.g. for PLMA₃₉–PBzMA₉₇ volume fractions of 0.20–0.35) when heating dilute dispersions of such binary nanoparticle mixtures up to 150 °C. A mechanism involving both chain expulsion/insertion and micelle fusion/fission is proposed to account for these unexpected observations.

Dilute dispersions of poly(lauryl methacrylate)-poly(benzyl methacrylate) diblock copolymer spheres of differing mean diameter are mixed and thermally annealed at 150 °C to produce either spherical or non-spherical nanoparticles of intermediate size.     

Silica nanoparticle-loaded thermoresponsive block copolymer vesicles: a new post-polymerization encapsulation strategy and thermally triggered release

A thermoresponsive amphiphilic diblock copolymer that can form spheres, worms or vesicles in aqueous media at neutral pH by simply raising the dispersion temperature from 1 °C (spheres) to 25 °C (worms) to 50 °C (vesicles) is prepared via polymerization-induced self-assembly (PISA). Heating such an aqueous copolymer dispersion from 1 °C up to 50 °C in the presence of 19 nm glycerol-functionalized silica nanoparticles enables this remarkable ‘shape-shifting’ behavior to be exploited as a new post-polymerization encapsulation strategy. The silica-loaded vesicles formed at 50 °C are then crosslinked using a disulfide-based dihydrazide reagent. Such covalent stabilization enables the dispersion to be cooled to room temperature without loss of the vesicle morphology, thus aiding characterization and enabling the loading efficiency to be determined as a function of both copolymer and silica concentration. Small-angle X-ray scattering (SAXS) analysis indicated a mean vesicle membrane thickness of approximately 20 ± 2 nm for the linear vesicles and TEM studies confirmed encapsulation of the silica nanoparticles within these nano-objects. After removal of the non-encapsulated silica nanoparticles via multiple centrifugation–redispersion cycles, thermogravimetric analysis indicated that vesicle loading efficiencies of up to 86% can be achieved under optimized conditions. Thermally-triggered release of the silica nanoparticles is achieved by cleaving the disulfide bonds at 50 °C using tris(2-carboxyethyl)phosphine (TCEP), followed by cooling to 20 °C to induce vesicle dissociation. SAXS is also used to confirm the release of silica nanoparticles by monitoring the disappearance of the structure factor peak arising from silica–silica interactions.

A loading efficiency of up to 86% is achieved for silica nanoparticles encapsulated within crosslinkable redox-sensitive thermoresponsive diblock copolymer vesicles in water at 50 °C; triggered release is also demonstrated for this system.     

Aldehyde-functional thermoresponsive diblock copolymer worm gels exhibit strong mucoadhesion

A series of thermoresponsive diblock copolymer worm gels is prepared via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate using a water-soluble methacrylic precursor bearing pendent cis-diol groups. Selective oxidation using an aqueous solution of sodium periodate affords the corresponding aldehyde-functional worm gels. The aldehyde groups are located within the steric stabilizer chains and the aldehyde content can be adjusted by varying the periodate/cis-diol molar ratio. These aldehyde-functional worm gels are evaluated in terms of their mucoadhesion performance with the aid of a fluorescence microscopy-based assay. Using porcine urinary bladder mucosa as a model substrate, we demonstrate that these worm gels offer a comparable degree of mucoadhesion to that afforded by chitosan, which is widely regarded to be a ‘gold standard’ positive control in this context. The optimum degree of aldehyde functionality is approximately 30%: lower degrees of functionalization lead to weaker mucoadhesion, whereas higher values compromise the desirable thermoresponsive behavior of these worm gels.

Optimizing the aldehyde content of thermoresponsive diblock copolymer worm gels via periodate oxidation leads to mucoadhesion performance comparable to that of chitosan (a gold standard positive control) in a fluorescence assay using porcine mucosa.     

Aqueous dispersion polymerization: a new paradigm for in situ block copolymer self-assembly in concentrated solution

Reversible addition-fragmentation chain transfer polymerization has been utilized to polymerize 2-hydroxypropyl methacrylate (HPMA) using a water-soluble macromolecular chain transfer agent based on poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC). A detailed phase diagram has been elucidated for this aqueous dispersion polymerization formulation that reliably predicts the precise block compositions associated with well-defined particle morphologies (i.e., pure phases). Unlike the ad hoc approaches described in the literature, this strategy enables the facile, efficient, and reproducible preparation of diblock copolymer spheres, worms, or vesicles directly in concentrated aqueous solution. Chain extension of the highly hydrated zwitterionic PMPC block with HPMA in water at 70 °C produces a hydrophobic poly(2-hydroxypropyl methacrylate) (PHPMA) block, which drives in situ self-assembly to form well-defined diblock copolymer spheres, worms, or vesicles. The final particle morphology obtained at full monomer conversion is dictated by (i) the target degree of polymerization of the PHPMA block and (ii) the total solids concentration at which the HPMA polymerization is conducted. Moreover, if the targeted diblock copolymer composition corresponds to vesicle phase space at full monomer conversion, the in situ particle morphology evolves from spheres to worms to vesicles during the in situ polymerization of HPMA. In the case of PMPC(25)-PHPMA(400) particles, this systematic approach allows the direct, reproducible, and highly efficient preparation of either block copolymer vesicles at up to 25% solids or well-defined worms at 16-25% solids in aqueous solution.     

Oxidation-responsive framboidal triblock copolymer vesicles prepared by photoinitiated RAFT seeded emulsion polymerization

Stimulus-responsive vesicles have broad applications in a variety of areas. Herein, oxidation-responsive framboidal triblock copolymer vesicles are prepared by photoinitiated RAFT seeded emulsion polymerization of a thioether-functionalized monomer using diblock copolymer vesicles as seeds. The obtained framboidal vesicles can transform into worms or spheres in the presence of reactive oxygen species, which can be further used for controlled release of cargos (e.g., silica nanoparticles).     

水相光引发聚合诱导自组装制备嵌段共聚物纳米材料

本文以聚甲基丙烯酸甘油酯(PGMA)作为大分子链转移剂、甲基丙烯酸羟丙酯(HPMA)为单体、苯基钠盐-三甲基苯甲酰亚磷酸盐(SPTP)为引发剂,通过水相光引发可逆加成-断裂链转移(RAFT)分散聚合制备了一系列PGMA-b-PHPMA共聚物纳米材料。考察了水相光引发聚合诱导自组装的反应动力学,在温和条件下(水相、可见光和室温)成功得到不同形貌的聚合物纳米材料(球形、纤维和囊泡),并进一步探究了反应条件对嵌段聚合物形貌的影响。聚合反应的激活或暂停都可以通过对光源的简单"开/关"进行控制。     

Recent Advances in Polymerization-Induced Self-Assembly (PISA) Syntheses in Non-Polar Media

It is well-known that polymerization-induced self-assembly (PISA) is a powerful and highly versatile technique for the rational synthesis of colloidal dispersions of diblock copolymer nanoparticles, including spheres, worms or vesicles. PISA can be conducted in water, polar solvents or non-polar media. In principle, the latter formulations offer a wide range of potential commercial applications. However, there has been just one review focused on PISA syntheses in non-polar media and this prior article was published in 2016. The purpose of the current review article is to summarize the various advances that have been reported since then. In particular, PISA syntheses conducted using reversible addition-fragmentation chain-transfer (RAFT) polymerization in various n-alkanes, poly(α-olefins), mineral oil, low-viscosity silicone oils or supercritical CO₂ are discussed in detail. Selected formulations exhibit thermally induced worm-to-sphere or vesicle-to-worm morphological transitions and the rheological properties of various examples of worm gels in non-polar media are summarized. Finally, visible absorption spectroscopy and small-angle X-ray scattering (SAXS) enable in situ monitoring of nanoparticle formation, while small-angle neutron scattering (SANS) can be used to examine micelle fusion/fission and chain exchange mechanisms.     

Low‐Temperature Synthesis of Thermoresponsive Diblock Copolymer Nano‐Objects via Aqueous Photoinitiated Polymerization‐Induced Self‐Assembly (Photo‐PISA) using Thermoresponsive Macro‐RAFT Agents

Photoinitiated reversible addition‐fragmentation chain transfer (RAFT) dispersion polymerization of 2‐hydroxypropyl methacrylate is conducted in water at low temperature using thermoresponsive copolymers of 2‐(2‐methoxyethoxy) ethyl methacrylate and oligo(ethylene glycol) methacrylate (M_n = 475 g mol⁻¹) as the macro‐RAFT agent. Kinetic studies confirm that quantitative monomer conversion is achieved within 15 min of visible‐light irradiation (405 nm, 0.5 mW cm⁻²), and good control is maintained during the polymerization. The polymerization can be temporally controlled by a simple “ON/OFF” switch of the light source. Finally, thermoresponsive diblock copolymer nano‐objects with a diverse set of complex morphologies (spheres, worms, and vesicles) are prepared using this particular formulation.

     

Polymerization‐induced self‐assembly of block copolymer through dispersion RAFT polymerization in ionic liquid

Polymerization‐induced self‐assembly of block copolymer through dispersion RAFT polymerization has been demonstrated to be a valid method to prepare block copolymer nano‐objects. However, volatile solvents are generally involved in this preparation. Herein, the in situ synthesis of block copolymer nano‐objects of poly(ethylene glycol)‐block‐polystyrene (PEG‐b‐PS) in the ionic liquid of 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([BMIN][PF₆]) through the macro‐RAFT agent mediated dispersion polymerization is investigated. It is found that the dispersion RAFT polymerization of styrene in the ionic liquid of [BMIN][PF₆] runs faster than that in the alcoholic solvent, and the dispersion RAFT polymerization in the ionic liquid affords good control over the molecular weight and the molecular weight distribution of the PEG‐b‐PS diblock copolymer. The morphology of the in situ synthesized PEG‐b‐PS diblock copolymer nano‐objects, e.g., nanospheres and vesicles, in the ionic liquid is dependent on the polymerization degree of the solvophobic block and the concentration of the fed monomer, which is somewhat similar to those in alcoholic solvent. It is anticipated that the dispersion RAFT polymerization in ionic liquid broads a new way to prepare block copolymer nano‐objects. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1517–1525     

Influence of structure and solubility of chain transfer agents on the RAFT control of dispersion polymerisation in scCO2

Reversible addition–fragmentation chain transfer (RAFT) dispersion polymerisation of methyl methacrylate (MMA) is performed in supercritical carbon dioxide (scCO₂) with 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) present as chain transfer agent (CTA) and surprisingly shows good control over PMMA molecular weight. Kinetic studies of the polymerisation in scCO₂ also confirm these data. By contrast, only poor control of MMA polymerisation is obtained in toluene solution, as would be expected for this CTA which is better suited for acrylates. In this regard, we select a range of CTAs and use them to determine the parameters that must be considered for good control in dispersion polymerisation in scCO₂. A thorough investigation of the nucleation stage during the dispersion polymerisation reveals an unexpected “in situ two-stage” mechanism that strongly determines how the CTA works. Finally, using a novel computational solvation model, we identify a correlation between polymerisation control and degree of solubility of the CTAs. All of this ultimately gives rise to a simple, elegant and counterintuitive guideline to select the best CTA for RAFT dispersion polymerisation in scCO₂.

RAFT dispersion polymerisation of methyl methacrylate is performed in scCO₂ with 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) present as chain transfer agent (CTA) and surprisingly shows good control over PMMA molecular weight.     

Polymerization-induced self-assembly of amino-acid-based nano-objects by reversible addition–fragmentation chain-transfer dispersion polymerization

A series of amino-acid-based amphiphilic diblock copolymer nano-objects having different morphologies were developed by reversible addition–fragmentation chain-transfer (RAFT) dispersion polymerization of styrene (St) in methanol. This was mediated by six different hydrophilic poly(N-acryloyl amino acid) macro-chain transfer agents (CTAs), including three carboxylic-acid-containing ones, poly(N-acryloyl-l -proline) (PAProOH), poly(N-acryloyl-4-trans-hydroxy-l -proline) (PAHypOH), and poly(N-acryloyl-l -threonine) (PAThrOH) prepared by RAFT polymerization, and their methyl ester forms, PAProOMe, PAHypOMe, and PAThrOMe. The effects of polymerization conditions on RAFT dispersion polymerization of St using a dithiocarbamate-terminated PAProOH was investigated. A systematic study of the effects of monomer conversion and concentration afforded the formation of various morphologies (i.e., spheres, worms, and vesicles). The effects of hydrogen-bonding and ionic interactions of the macro-CTAs on the assembled structures of the nano-objects were evaluated using six different macro-CTAs. Transforming the products from methanol to water via dialysis produced amino-acid-based block copolymer nano-objects, exhibiting pH-responsive morphological change, in aqueous solution.     

Synthesis and self‐assembly of stimuli‐responsive amphiphilic block copolymers based on polyhedral oligomeric silsesquioxane

A novel POSS‐containing methacrylate monomer (HEMAPOSS) was fabricated by extending the side chain between polyhedral oligomeric silsesquioxane (POSS) unit and methacrylate group, which can efficiently decrease the steric hindrance in free‐radical polymerization of POSS‐methacrylate monomer. POSS‐containing homopolymers (PHEMAPOSS) with a higher degree of polymerization (DP) can be prepared using HEMAPOSS monomer via reversible addition–fragmentation chain transfer (RAFT) polymerization. PHEMAPOSS was further used as the macro‐RAFT agent to construct a series of amphiphilic POSS‐containing poly(N, N‐dimethylaminoethyl methacrylate) diblock copolymers, PHEMAPOSS‐b‐PDMAEMA. PHEMAPOSS‐b‐PDMAEMA block copolymers can self‐assemble into a plethora of morphologies ranging from irregular assembled aggregates to core‐shell spheres and further from complex spheres (pearl‐necklace‐liked structure) to large compound vesicles. The thermo‐ and pH‐responsive behaviors of the micelles were also investigated by dynamic laser scattering, UV spectroscopy, SEM, and TEM. The results reveal the reversible transition of the assembled morphologies from spherical micelles to complex micelles was realized through acid‐base control. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2669‐2683     

一种两亲性嵌段共聚物胶束的制备及其对叶酸的负载和控制释放

采用可逆加成-断裂链转移(RAFT)聚合合成了以丙烯酸异丁酯(IBA)、甲基丙烯酸2-二甲氨乙酯(DMAEMA)无规共聚嵌段与聚丙烯酸-2-羟丙酯(PHPA)组成的两亲性两嵌段共聚物(P( IBA-co-DMAEMA)-b-PHPA),并用凝胶渗透色谱(GPC)、核磁共振波谱(1H-NMR)及红外光谱(FTIR)对其进...     

Preparation of pH- and reductive-responsive prodrug nanoparticles via polymerization-induced self-assembly

pH- and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly (PISA). First, reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and camptothecin prodrug monomer (CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P (DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate (BzMA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell (PHPMA), the drug-conjugated middle layer (P(DIPEMA-co-CPTM)) and the PBzMA core, and relatively high concentration (250 mg/g). The prodrug nanoparticles can respond to two stimuli (reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin (CPT) within the prodrug nanoparticles could be effectively triggered. pH-Induced hydrophobic/ hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.     

Free-standing metal–organic framework (MOF) monolayers by self-assembly of polymer-grafted nanoparticles

We report a general method for the synthesis of free-standing, self-assembled MOF monolayers (SAMMs) at an air–water interface using polymer-brush coated MOF nanoparticles. UiO-66, UiO-66-NH₂, and MIL-88B-NH₂ were functionalized with a catechol-bound chain-transfer agent (CTA) to graft poly(methyl methacrylate) (PMMA) from the surface of the MOF using reversible addition-fragmentation chain transfer polymerization (RAFT). The polymer-coated MOFs were self-assembled at the air–water interface into monolayer films ∼250 nm thick and capable of self-supporting at a total area of 40 mm². Mixed-particle films were prepared through the assembly of MOF mixtures, while multilayer films were achieved through sequential transfer of the monolayers to a glass slide substrate. This method offers a modular and generalizable route to fabricate thin-films with inherent porosity and sub-micron thickness composed of a variety of MOF particles and functionalities.

We report a general method for the synthesis of free-standing, self-assembled MOF monolayers (SAMMs) at an air–water interface using polymer-brush coated MOF nanoparticles.     

Exploiting in situ NMR to monitor the formation of a metal–organic framework

The formation processes of metal–organic frameworks are becoming more widely researched using in situ techniques, although there remains a scarcity of NMR studies in this field. In this work, the synthesis of framework MFM-500(Ni) has been investigated using an in situ NMR strategy that provides information on the time-evolution of the reaction and crystallization process. In our in situ NMR study of MFM-500(Ni) formation, liquid-phase ¹H NMR data recorded as a function of time at fixed temperatures (between 60 and 100 °C) afford qualitative information on the solution-phase processes and quantitative information on the kinetics of crystallization, allowing the activation energies for nucleation (61.4 ± 9.7 kJ mol⁻¹) and growth (72.9 ± 8.6 kJ mol⁻¹) to be determined. Ex situ small-angle X-ray scattering studies (at 80 °C) provide complementary nanoscale information on the rapid self-assembly prior to MOF crystallization and in situ powder X-ray diffraction confirms that the only crystalline phase present during the reaction (at 90 °C) is phase-pure MFM-500(Ni). This work demonstrates that in situ NMR experiments can shed new light on MOF synthesis, opening up the technique to provide better understanding of how MOFs are formed.

A new in situ NMR methodology for studying the formation processes of MOFs is reported, supported by SAXS and PXRD experiments. Synthesis of a phosphonate-based MOF is described, from molecular aggregation through to nucleation and crystallisation.     

The doubly thermo-responsive triblock copolymer nanoparticles prepared through seeded RAFT polymerization

The doubly thermo-responsive triblock copolymer nanoparticles of polystyrene-block-poly(N-isopropylacrylamide)-block-poly[N,N-(dimethylamino) ethyl methacrylate] (PS-b-PNIPAM-b-PDMAEMA) are successfully prepared through the seeded RAFT polymerization in situ by using the PS-b-PNIPAM-TTC diblock copolymer nanoparticles as the seed. The seeded RAFT polymerization undergoes a pseudo-first-order kinetics procedure, and the molecular weight increases with the monomer conversion linearly. The hydrodynamic diameter (D _h) of the triblock copolymer nanoparticles increases with the extension of the PDMAEMA block. In addition, the double thermo-response behavior of the PS-b-PNIPAM-b-PDMAEMA nanoparticles is detected by turbidity analysis, temperature-dependent 1H-NMR analysis, and DLS analysis. The seeded RAFT polymerization is believed as a valid method to prepare triblock copolymer nanoparticles containing two thermo-responsive blocks.