Jieshu Qian

Nanofiber micelles from the self-assembly of block copolymers

Micelles are formed when block copolymers are dissolved in solvents selective for one of the blocks. In contrast to micelles formed by surfactants, block copolymer micelles are generally more robust, and this opens the door to many applications. This article examines the formation and structure of fiber-like or filamentous micelles, with cross-sections of nanometer dimensions. These fascinating objects are currently under investigation for drug delivery applications, as impact modifiers for plastics, as templates for the deposition of metal nanoparticles and as precursors to nanoscale ceramics. Moreover, in some cases, studies of their formation and fragmentation are beginning to provide insight into the generation of protein fibers, such as actin or amyloid fibers, derived from soluble cytosolic protein precursors.

Uniform, High Aspect Ratio Fiber-like Micelles and Block Co-micelles with a Crystalline π-Conjugated Polythiophene Core by Self-Seeding

Monodisperse fiber-like micelles with a crystalline π-conjugated polythiophene core with lengths up to ca. 700 nm were successfully prepared from the diblock copolymer poly(3-hexylthiophene)-block-polystyrene using a one-dimensional self-seeding technique. Addition of a polythiophene block copolymer with a different corona-forming block to the resulting nanofibers led to the formation of segmented B-A-B triblock co-micelles by crystallization-driven seeded growth. The key to these advances appears to be the formation of a relatively defect-free crystalline micelle core under the self-seeding conditions.

Self-seeding in one dimension: an approach to control the length of fiberlike polyisoprene-polyferrocenylsilane block copolymer micelles.

Self-seeding is a phenomenon unique for polymer crystallization. Polymers have difficulty in crystallizing and, in most cases, only part of each polymer chain can be accommodated in the crystal lattice. As a result, polymers form crystals with lamellar structures terminated by surfaces containing chain folds. If long chains have to be integrated into the crystal in a short time, they will do so at the expense of lower crystallinity. As a consequence, polymer crystals inevitably consist of regions with different chain order and conformational entropy. Polymer crystals have a broad range of melting temperatures whose values depend upon the details of the crystallization process. In a typical self-seeding experiment, a crystalline polymer in the bulk state or suspended in a solvent is heated slightly above its normal melting point (as determined, for example, by differential scanning calorimetry; DSC) so that no residual crystals can be detected optically or spectroscopically. Cooling this melt or solution leads to the formation of polymer single crystals, normally in the form of thin plates uniform in size and thickness, which can be ideally suited for further applications. These single crystals are thought to be initiated by submicroscopic nuclei that survived the dissolution procedure. Since the discovery of self-seeding in the 1960s the process has attracted attention as a means of controlling the nucleation step of polymer crystallization without the need for external nucleating agents, to form uniform single crystals of homopolymers and block copolymers and also for materials applications. Polyferrocenyldimethylsilane (PFS) is a crystalline metalcontaining polymer with a range of interesting properties. PFS block copolymers and closely related materials selfassemble to form elongated micelles with a semicrystalline core. They are the only currently known synthetic polymers to form fiberlike micelles by a mechanism resembling that for the formation of amyloid fibers from soluble protein. Thus soluble polymeric “monomers” consisting of block copolymer unimers condense onto both ends of seed structures present in, or intentionally added to, the solution. PFS block copolymer fiber formation involves a conformation change driven by epitaxial crystallization of PFS moieties onto the open ends of the PFS core of existing micelles or seeds obtained by subjecting preformed fiberlike micelles to mild sonication. Thus, the number of micelles at the end of the growth process is determined by the number of seeds present at the beginning. Moreover the seeded growth experiments permit exquisite control over the types of structures obtained. For example, one type of PFS block copolymer such as PI-PFS (PI = polyisoprene) can be used to form the seed structure, and a different type of PFS block copolymer such as PFSPDMS (PDMS = polydimethylsiloxane) can be grown off the ends. In this way striking novel architectures referred to as “triblock co-micelles” can be prepared. 10] Our recent work targets a deeper understanding of the self-assembly process for PFS block copolymers in order to develop principles that can be extended to other coil-crystalline block copolymers. This may allow access to processable suspensions of semiflexible nanowires with useful optical or electronic properties. With proper control over their length and dimensions, such structures could be incorporated into optoelectronic devices or used in other applications. In 2009, Reiter and co-workers examined the mechanism of self-seeding in the melt for PFS homopolymer single crystals and for single crystals formed by P2VP-PEO block copolymers. (P2VP = poly(2-vinylpyridine), PEO = poly(ethylene oxide)). They showed for these two systems that the number density of the regenerated crystals decreased exponentially with the increase of the dissolution temperature but did not vary with the dissolution time. They also found a correlation in molecular orientation between a starting single crystal and the regenerated crystal clones formed through the self-seeding process. Their experiments established that single-crystal growth by self-seeding operates under thermodynamic control, consistent with the idea that upon heating, the less perfect crystals will melt and more perfect crystallites will survive. It is not a kinetic effect associated with polymer conformational memory effects. [*] J. S. Qian, Dr. G. Guerin, Y. J. Lu, G. Cambridge, Prof. M. A. Winnik Department of Chemistry, University of Toronto 80 St. George Street Toronto, Ontario, M5S 3H6 (Canada) Fax: (+ 1)416-978-0541 E-mail: mwinnik@chem.utoronto.ca

Self-Seeding in One Dimension: A Route to Uniform Fiber-like Nanostructures from Block Copolymers with a Crystallizable Core-Forming Block

One-dimensional micelles formed by the self-assembly of crystalline-coil poly(ferrocenyldimethylsilane) (PFS) block copolymers exhibit self-seeding behavior when solutions of short micelle fragments are heated above a certain temperature and then cooled back to room temperature. In this process, a fraction of the fragments (the least crystalline fragments) dissolves at elevated temperature, but the dissolved polymer crystallizes onto the ends of the remaining seed fragments upon cooling. This process yields longer nanostructures (up to 1 μm) with uniform width (ca. 15 nm) and a narrow length distribution. In this paper, we describe a systematic investigation of factors that affect the self-seeding behavior of PFS block copolymer micelle fragments. For PI(1000)-PFS(50) (the subscripts refer to the number average degree of polymerization) in decane, these factors include the presence of a good solvent (THF) for PFS and the effect of annealing the fragments prior to the self-seeding experiments. THF promoted the dissolution of the micelle fragments, while preannealing improved their stability. We also extended our experiments to other PFS block copolymers with different corona-forming blocks. These included PI(637)-PFS(53) in decane, PFS(60)-PDMS(660) in decane (PDMS = polydimethylsiloxane), and PFS(30)-P2VP(300) in 2-propanol (P2VP = poly(2-vinylpyridine)). The most remarkable result of these experiments is our finding that the corona-forming chain plays an important role in affecting how the PFS chains crystallize in the core of the micelles and, subsequently, the range of temperatures over which the micelle fragments dissolve. Our results also show that self-seeding is a versatile approach to generate uniform PFS fiber-like nanostructures, and in principle, the method should be extendable to a wide variety of crystalline-coil block copolymers.

Enhancing the Photoluminescence of Polymer-Stabilized CdSe/CdS/ZnS Core/Shell/Shell and CdSe/ZnS Core/Shell Quantum Dots in Water through a Chemical-Activation Approach

We report a method for preparing highly photoluminescent, water-soluble CdSe/CdS/ZnS core/shell/shell and CdSe/ZnS core/shell quantum dots (QDs) colloidally stabilized by double hydrophilic copolymers. The polymers, either a diblock copolymer poly(ethylene glycol-b-2-N,N-dimethylaminoethyl methacrylate) (PEG-b-PDMA) or a statistical copolymer poly(oligoethylene glycol methacrylate-co-2-N,N-dimethylaminoethyl methacrylate) (POEG-co-PDMA), were able to replace the hexadecylamine (HDA) or trioctylphosphine oxide (TOPO) ligands on the surface of the as-synthesized QDs and impart water-solubility and colloidal stability to the QD nanocrystals. In water, the [CdSe/ZnS]/POEG-co-PDMA colloids were present in the form of aggregates with a mean apparent hydrodynamic radius Rh of 54 nm and a narrow size distribution. Although the photoluminescence (PL) quantum yield (QY) of the polymer-treated QDs decreased upon transfer from an organic medium to water, much of this loss in brightness could be restored by the addition to the solution of an excess of a water-soluble primary amine such as 3-amino-propanol (APP). This chemical-activation strategy of adding primary amines as PL activators to polymer-stabilized QDs did not lead to a spectral shift of either the absorption or emission of the QDs in water.

Peptide-glycosaminoglycan cluster formation involving cell penetrating peptides.

Glycosaminoglycans (GAGs) affect the efficiency of cellular uptake of a wide range of cell penetrating peptides (CPPs). GAGs have been proposed to cluster with CPPs at the cell surface before uptake but little is known about the formation or stability of CPP-GAG clusters. Here we apply a combination of heparin affinity chromatography, dynamic light scattering, and fluorescence spectroscopy to characterize the formation, stability, and size of the clusters formed between CPPs and heparin. Under conditions similar to those used in cell uptake experiments the CPP, penetratin (Antp), was observed to form significantly more stable clusters with heparin than the CPP TAT, despite TAT showing a comparable affinity for heparin. This difference in cluster stability may explain the origins of the preferred cell uptake pathways followed by Antp and TAT, and may be an important parameter for optimizing the efficiency of designed CPP delivery vectors.

Synthesis and Mass Cytometric Analysis of Lanthanide-Encoded Polyelectrolyte Microgels

This article describes the synthesis and characterization of two series of functional polyelectrolyte copolymer microgels intended for bioassays based upon mass cytometry, a technique that detects metals by inductively coupled plasma mass spectrometry (ICP-MS). The microgels were loaded with Eu(III) ions, which were then converted in situ to EuF(3) nanoparticles (NPs). Both types of microgels are based upon copolymers of N-isopropylacrylamide (NIPAm) and methacrylic acid (MAA), poly(NIPAm/VCL/MAA) (VCL = N-vinylcaprolactam, V series), and poly(NIPAm/MAA/PEGMA) (PEGMA = poly(ethylene glycol)methacrylate, PG series). Very specific conditions (full neutralization of the MAA groups) were required to confine the EuF(3) NPs to the core of the microgels. We used mass cytometry to measure the number and the particle-to-particle variation of Eu ions per microgel. By controlling the amount of EuCl(3) added to the neutralized microgels. we could vary the atomic content of individual microgels from ca. 10(6) to 10(7) Eu atoms, either in the form of Eu(3+) ions or EuF(3) NPs. Leaching profiles of Eu ions from the hybrid microgels were measured by traditional ICP-MS.

Uniform electroactive fibre-like micelle nanowires for organic electronics

Micelles formed by the self-assembly of block copolymers in selective solvents have attracted widespread attention and have uses in a wide variety of fields, whereas applications based on their electronic properties are virtually unexplored. Herein we describe studies of solution-processable, low-dispersity, electroactive fibre-like micelles of controlled length from π-conjugated diblock copolymers containing a crystalline regioregular poly(3-hexylthiophene) core and a solubilizing, amorphous regiosymmetric poly(3-hexylthiophene) or polystyrene corona. Tunnelling atomic force microscopy measurements demonstrate that the individual fibres exhibit appreciable conductivity. The fibres were subsequently incorporated as the active layer in field-effect transistors. The resulting charge carrier mobility strongly depends on both the degree of polymerization of the core-forming block and the fibre length, and is independent of corona composition. The use of uniform, colloidally stable electroactive fibre-like micelles based on common π-conjugated block copolymers highlights their significant potential to provide fundamental insight into charge carrier processes in devices, and to enable future electronic applications.

A high-sensitivity lanthanide nanoparticle reporter for mass cytometry: tests on microgels as a proxy for cells.

This paper addresses the question of whether one can use lanthanide nanoparticles (e.g., NaHoF4) to detect surface biomarkers expressed at low levels by mass cytometry. To avoid many of the complications of experiments on live or fixed cells, we carried out proof-of-concept experiments using aqueous microgels with a diameter on the order of 700 nm as a proxy for cells. These microgels were used to test whether nanoparticle (NP) reagents would allow the detection of as few as 100 proteins per “cell” in cell-by-cell assays. Streptavidin (SAv), which served as the model biomarker, was attached to the microgel in two different ways. Covalent coupling to surface carboxyls of the microgel led to large numbers (>104) of proteins per microgel, whereas biotinylation of the microgel followed by exposure to SAv led to much smaller numbers of SAv per microgel. Using mass cytometry, we compared two biotin-containing reagents, which recognized and bound to the SAvs on the microgel. One was a metal chelating polymer (MCP), a biotin end-capped polyaspartamide containing 50 Tb3+ ions per probe. The other was a biotinylated NaHoF4 NP containing 15 000 Ho atoms per probe. Nonspecific binding was determined with bovine serum albumin (BSA) conjugated microgels. The MCP was effective at detecting and quantifying SAvs on the microgel with covalently bound SAv (20 000 SAvs per microgel) but was unable to give a meaningful signal above that of the BSA-coated microgel for the samples with low levels of SAv. Here the NP reagent gave a signal 2 orders of magnitude stronger than that of the MCP and allowed detection of NPs ranging from 100 to 500 per microgel. Sensitivity was limited by the level of nonspecific adsorption. This proof of concept experiment demonstrates the enhanced sensitivity possible with NP reagents in cell-by-cell assays by mass cytometry.

Seeded Growth and Solvent-Induced Fragmentation of Fiberlike Polyferrocenylsilane–Polyisoprene Block Copolymer Micelles

Addition of a concentrated solution of PI(1000) -PFS(50) dissolved in THF to a solution of PI(1000) -PFS(50) seed micelles in decane led to the formation of uniform elongated fiberlike micelles with a narrow length distribution. When additional THF (>10 vol.-%) was added to the micelles, the micelle length decreased and the contour-length distribution broadened. This effect was shown to be inconsistent with a transition to an equilibrium, in which individual polymer molecules dissociated from and added to existing micelles. Rather, it appears that the polar solvent induced fragmentation of the fiberlike micelles.