Xiaodong Fan

Miktoarm star polymers with poly(N-isopropylacrylamide) or poly(oligo(ethylene glycol) methacrylate) as building blocks: synthesis and comparison of thermally-responsive behaviors

We synthesized two thermally-responsive miktoarm star polymers in which poly(N-isopropylacrylamide) (PNIPAM) or poly(oligo(ethylene glycol) methacrylate) (POEGMA) served as the thermosensitive building blocks. Firstly, linear methoxypolyethylene glycol (PEG) with β-cyclodextrin (β-CD) bearing about six chlorines as a terminal (PEG-CD-Clx, x ≈ 6) was synthesized. Then, the thermally-responsive miktoarm star polymer, PEG-CD-PNIPAMx or PEG-CD-POEGMAx, was achieved by atom transfer radical polymerization using N-isopropylacrylamide or oligo(ethylene glycol) methacrylate as the monomer and PEG-CD-Clx as the macroinitiator. The obtained miktoarm star polymers were comprised of a β-CD core, a PEG arm and about six PNIPAM or POEGMA arms. Furthermore, the thermally-responsive behaviors of the miktoarm star polymers were investigated by a combination of UV-vis spectroscopy, DLS, TEM, 1H NMR, fluorescence spectroscopy and DCS. Above the LCST of the polymers in aqueous solution, PEG-CD-PNIPAMx can self-assemble into nano-structures with PNIPAM as the core and PEG as the corona, whereas PEG-CD-POEGMAx self-assembled into nano-architectures possessing hydrophilic surfaces which were constructed by the hydrated oligo(ethylene glycol) side chains of the POEGMA arms. The hydrophobic moiety of the nano-architectures was formed by the methacrylate backbone and the dehydrated oligo(ethylene glycol) side chains of POEGMA. Furthermore, it was found that the thermally-induced dehydration of PEG-CD-PNIPAMx is completely different from that of PEG-CD-POEGMAx. For the former, the dehydration occurs abruptly and intensively near the LCST of PEG-CD-PNIPAMx, whereas the dehydration for the latter is gradual and continuous throughout the whole temperature rise. The architecture of the nano-assemblies formed by PEG-CD-PNIPAMx or PEG-CD-POEGMAx was affected by the thermally-induced dehydration of the polymers.

A branching point thermo and pH dual-responsive hyperbranched polymer based on poly(N-vinylcaprolactam) and poly(N,N-diethyl aminoethyl methacrylate)

We report the design and synthesis of a branching point stimuli-responsive hyperbranched polymer based on poly(N-vinylcaprolactam) and poly(N,N-diethylaminoethyl methacrylate) through combined “A2 + BxC” (x > 2) double monomer polymerization and parallel click reaction. The results of ultraviolet-visible spectrophotometry and dynamic light scattering (DLS) indicated that the resultant hyperbranched polymer possesses thermo and pH dual-responsive properties and presents gradient phase transition behaviors under appropriate solution pH and temperature conditions. The dual-responsive properties are independent of the two grafted linear polymer components and hyperbranched structure. Interestingly, fluorescence spectrophotometry studies have revealed that hyperbranched polymer aqueous solutions show different encapsulation behaviors toward water-soluble methyl orange or oil-soluble lonidamine molecules below and above the critical micelle concentration (CMC). The different aggregation states of hyperbranched polymers with different encapsulation microenvironments, such as dot-like unimolecular micelles below CMC and spherical multimolecular micelles above CMC, were confirmed via DLS and transmission electron microscopy. The aggregation states directly indicated the level of encapsulation ability.

Preparation and properties of cyclodextrin/PNIPAm microgels.

A two-stage precipitation polymerization in aqueous solution was used to prepare beta-cyclodextrin/poly(N-isopropylacrylamide) (beta-CD/PNIPAm) core-shell microgels. At the first stage, core microgels with CD moieties were synthesized by precipitation copolymerization of N-isopropylacrylamide (NIPAm) with a monovinyl beta-CD monomer. At the second stage, using the core particles as seeds, PNIPAm shell were further added onto the seeds by NIPAm polymerization. The microgels were characterized by means of Zetasizer Nano-ZS dynamic light scattering, TEM, IR, NMR, DSC, and TGA measurements. Using paeonol as a model drug molecule, the release behaviors of the microgels were investigated. The result indicates that the core-shell microgels could respond to change in temperature. Furthermore, the release of paeonol was related to supramolecular inclusion behavior of beta-CD and temperature sensitivity of PNIPAm.

Nonionic Cyclodextrin Based Binary System with Upper and Lower Critical Solution Temperature Transitions via Supramolecular Inclusion Interaction

A nonionic binary aqueous interaction system consisting of β-cyclodextrin trimer (β-CD3) and naphthalene-terminated poly(ethylene glycol) (PEG-NP2), which has tunable upper critical solution temperature (UCST) behavior around room temperature and lower critical solution temperature (LCST) behavior at high temperature, was investigated. In the UCST transition, gel-like aggregates form because of supramolecular inclusion complexation between β-CD3 and PEG-NP2. During LCST transition, PEG-NP2 becomes insoluble in water, which results in its precipitation. The effects of concentration, stoichiometry of the two components, and electrolyte on UCST behavior are discussed. This study provides a new nonionic thermoresponsive material.

Morphology transitions of supramolecular hyperbranched polymers induced by double supramolecular driving forces

Tuning the morphology of supramolecular hyperbranched polymers (SHPs) in solution has theoretical and practical significance in SHP applications. This study successfully achieved SHP morphology transitions from branched supramolecular structures to spherical nanosized micelles in mixed solvents. Transmission electron microscopy, dynamic light scattering, 2D 1H NMR ROESY, and fluorescence emission spectroscopy confirmed these transitions. An AB2-type amphiphilic β-cyclodextrin (β-CD) monomer (Ada-CD2) exhibiting double supramolecular interactions was initially synthesized. SHPs based on Ada-CD2 were then formed in DMF–H2O mixed solvents through the host–guest inclusion interaction between β-CD and Ada. The formed SHPs disassembled with the addition of adamantane carboxylic sodium salt, which was a competitive guest. The SHPs reassembled into core–shell structured micelles based on the hydrophilic–hydrophobic interaction of the amphiphilic Ada-CD2 monomer.

A triple-monomer methodology to construct controllable supramolecular hyperbranched alternating polymers

A novel “D3–AC–E3” triple-monomer methodology was proposed to construct supramolecular hyperbranched alternating polymers. Two rigid homotritopic monomers tris(per-methylated pillar[5]arene) (D3) and tris(benzo-21-crown-7) (E3), and a heteroditopic monomer bearing a dialkylammonium salt and a neutral guest moiety, were prepared. The supramolecular hyperbranched alternating polymer was formed by selective binding interaction between the pillar[5]arene moiety with the neutral guest moiety and between the benzo-21-crown-7 group and the dialkylammonium salt group. The triple-monomer system was found to effectively avoid the formation of cyclic oligomers/gels/precipitates usually formed in the traditional “A2 + B3” double-monomer system. This study will be helpful in designing supramolecular hyperbranched polymers with controllable structure and function.

Phase transition dynamics and mechanism for backbone-thermoresponsive hyperbranched polyethers

In this study, a controllable thermo-induced phase transition process was first observed in the aqueous solution of backbone-thermoresponsive hyperbranched polyethers. According to the variable temperature UV-visible spectrophotometry, the phase transition process was extremely slow as temperature was set around lower critical solution temperature (LCST). Fluorescence tests showed that this slow phase transition behavior was related to the gradual thermally-induced dehydration of hyperbranched polyethers. Based on this unique behavior, the dynamics of phase transition was conveniently investigated by the temperature-jump method. Results showed that the dynamics of phase transition can be described by single exponential functions, and the dynamic parameters depended on temperature. Dynamic laser scattering and transmission electron microscopy revealed that the hyperbranched polyether self-assembled into micelles below its LCST, while the temperature-dependent aggregation occurred and complex micelles with larger size formed above LCST. Furthermore, the gradual aggregation process was in accordance with the rate-limited colloidal aggregation mechanism. Our research can contribute to the clarification of the dynamics and mechanism of this typical gradual phase transition process of backbone-thermoresponsive hyperbranched polymers, as well as their self-assembly and aggregation mechanisms.

Supramolecular Alternating Polymer from Crown Ether and Pillar[5]arene-Based Double Molecular Recognition for Preparation of Hierarchical Materials

A novel supramolecular alternating polymer is constructed based on double molecular recognition events of benzo-21-crown-7 with a secondary ammonium salt and of pillar[5]arene with a neutral guest. The resulting polymer is utilized to prepare hierarchical materials with different dimensionalities for the first time. These materials included zero-dimensional spherical aggregates, one-dimensional nanofibers, two-dimensional microstructured films, and three-dimensional ordered glue. This development will be helpful for designing and preparing supramolecular hierarchical materials with different dimensionalities.

Thermo and pH dual-controlled charge reversal amphiphilic graft copolymer micelles for overcoming drug resistance in cancer cells

Currently, multidrug resistance (MDR) is the major challenge of nanotechnology in cancer treatment. In this study, a series of amphiphilic poly(styrene-co-maleic anhydride)-graft-poly(2-(N,N-dimethylamino)ethyl methacrylate) graft copolymer [PSMA89-g-P(DMA16-co-SD)] micelles were prepared. PSMA89-g-P(DMA16-co-SD) graft copolymers were first synthesized by grafting different amounts of sulfadimethoxine (SD) onto PSMA89-g-P(DMA16-co-SD). The PSMA89-g-P(DMA16-co-SD56) micelles exhibited a thermo and pH dual-controlled charge reversal properties without cleavage of chemical bonds. The surface charge of PSMA89-g-P(DMA16-co-SD56) micelles reversed from positive to negative after the solution temperature increased from 25 °C to 37 °C at pH 7.4. However, when the pH value was adjusted to 6.8 at 37 °C, the surface charge became positive again. The thermo and pH dual-controlled charge reversal not only resulted in a controlled doxorubicin (DOX) release but also effectively enhanced the cellular uptake of DOX-loaded PSMA89-g-P(DMA16-co-SD56) micelles through electrostatic absorptive endocytosis. MTT assay demonstrated that DOX-loaded PSMA89-g-P(DMA16-co-SD56) micelles showed the highest inhibition growth of DOX-resistant ovarian carcinoma (A2780/DoxR) cells with pH 6.8 at 37 °C among those with pH 7.4 at 37 °C and pH 7.4 at 25 °C, leading to higher efficiency in overcoming MDR of A2780/DoxR cells. Therefore, PSMA89-g-P(DMA16-co-SD56) micelles can be used as intelligent drug-delivery systems to overcome MDR of cancer cells.

Synthesis and stimulus-responsive micellization of a well-defined H-shaped terpolymer

We describe the synthesis and self-assembly of a well-defined H-shaped terpolymer in this paper. A block copolymer of poly(ethylene glycol) (PEG) and poly(N,N-dimethylaminoethyl methacrylate) (PDMA), which bears an azido group at the diblock junction (PEG–N3(–PDMA)) was first prepared by atom transfer radical polymerization. Then, an alkynyl-terminated narrow distributed polytetrahydrofuran (PTHF-Alk) was synthesized as another building block via cationic ring opening polymerization. The well-defined H-shaped terpolymer was afforded by clicking PEG–N3(–PDMA) onto both chain-ends of PTHF-Alk. This H-shaped terpolymer can self-assemble into micelles with different sizes and morphologies at various solution pH values. The micellar size also exhibits temperature-dependence at pH 7.4 and 9.2. The variation of size and morphology of the micelles with the solution pH and temperature is ascribed to the pH- and thermo-responsive properties of the PDMA block.