Jun-Jie Yan

Synthesis of Thermo-Responsive Polymers With Both Tunable UCST and LCST

New water-soluble block copolymers of 2-(2-methoxyethoxy)ethyl methacrylate (MEO(2) MA), oligo(ethylene glycol) methacrylate (OEGMA), and N-(3-(dimethylamino) propyl) methacrylamide (DMAPMA) (poly(OEGMA-co-MEO(2) MA)-b-poly(DMAPMA)) were prepared via sequential reversible addition-fragmentation chain transfer (RAFT) polymerization. Selective quaternization of poly(DMAPMA) block gives poly(OEGMA-co-MEO(2) MA)-b-poly((3-[N-(3-methacrylamidopropyl)-N,N-dimethyl]ammoniopropane sulfonate)-co-N-(3-(dimethylamino) propyl) methacrylamide), such block copolymer exhibits double thermo-responsive behavior in water, poly(MEO(2) MA-co-OEGMA) block shows a lower critical solution temperature (LCST), and poly((3-[N-(3-methacrylamidopropyl)-N,N-dimethyl]ammoniopropane sulfonate)-co-N-(3-(dimethylamino) propyl) methacrylamide) block shows a upper critical solution temperature (UCST). Both of LCST and UCST can be controlled: LCST could be tuned by the fraction of OEGMA units in poly(OEGMA-co-MEO(2) MA), and UCST was found to be dependent on the degree of quaternization (DQ).

Synthesis of sequence-ordered polymers via sequential addition of monomers in one pot

Sequence-ordered polymers can be simply prepared in one pot via sequential monomer addition.

Polymerizing Nonfluorescent Monomers without Incorporating any Fluorescent Agent Produces Strong Fluorescent Polymers

Fluorescent polymers [ 1–5 ] have been widely utilized in applications such as bacteria detecting, [ 6 , 7 ] DNA probing, [ 8 , 9 ] signal amplifi cation in diagnostics tests, [ 10 , 11 ] and light-harvesting or antennae. [ 12 ] In general, all these fl uorescent polymers are either intrinsically fl uorescent (e.g., conjugated polymers) or functionalized with a fl uorophore, [ 4 , 13 ] otherwise, the polymer has no fl uorescence activity. All the fl uorescent polymers prepared via atom transfer radical polymerization (ATRP) or reversible addition-fragmentation chain transfer (RAFT) are those polymers that have been functionalized with fl uorophore. [ 14 ] Prior to our study, it was generally believed that polymerizing nonfl uorescent monomer without incorporating any fl uorescent agent only results in polymer without fl uorescent activity. However, it is surprising to fi nd that conventional ATRP or RAFT polymerization of nonfl uorescent monomers without incorporating any fl uorescent unit can produce fl uorescent polymers. This rather serendipitous discovery emerged during our investigation of preparation of multiblock polymer via poly(trithiocarbonate) (PTTC, M w is ≈ 2000) mediated RAFT polymerization of Nisopropyl acrylamide (NIPAM). It was found that there was a new, strong emission around 420 nm besides the emission of quantum dots when the prepared multiblock polymer was used to cap quantum dots (Figure S6 in the Supporting Information), and the subsequent experimental results showed that this new emission came from the multiblock polymer used. It is very surprising that although no fl uorescent agent was employed in the polymerization system, and the produced multiblock polymers have no any conventional fl uorophore unit, they show strong fl uorescence, similar to organic dyes. We have also checked all the similar polymers prepared via conventional ATRP or RAFT polymerization; however, there is no information available on their fl uorescence. [ 4 , 14–16 ]

Multi-responsive carbon nanotube gel prepared via ultrasound-induced assembly

Hyperbranched poly(amido amine) is grown from the surface of carbon nanotubesvia a multi-step Michael addition reaction, hence the amido and amine units are linked onto the surface of carbon nanotubes. These amido and amine units can facilitate the assembly of carbon nanotubes with other functional polymersviahydrogen bonds. The external ultrasound-stimulus is found to induce the assembly of functionalized multi-walled carbon nanotubes with linear poly(amido amine) into a smart carbon nanotube gel viahydrogen bonds. The notable advantages of this method are that the gelation is very fast and controlled by ultrasound strength, the formed carbon nanotube gels are not only responsive to some mechanical stimuli such as vigorous agitating, but also responsive to some chemical stimuli such as water and acids. The carbon nanotubes are homogenously embedded in the gel network, and the sol–gel switching is easily realized via heating and ultrasonicating. It is interesting that sonication can untangle the bundles of MWNT via breaking the van der Waals forces between them to disperse MWNTs at high temperature, but induce the assembly of MWNTs functionalized with poly(amido amine) viahydrogen bonds into a smart carbon nanotube based gel at room temperature.

Growing Hyperbranched Polymers Using Natural Sunlight

In nature, a sapling can grow into a big tree under irradiation of sunlight. In chemistry, a similar concept that a small molecule only exposing to sunlight grows into a hyperbranched macromolecule has not been realized by now. The achievement of the concept will be fascinating and valuable for polymer synthesis wherein sunlight is inexpensive, abundant, renewable, and nonpolluting. Herein, we report a new strategy in which small monomers can directly grow into big hyperbranched macromolecule under irradiation of sunlight without any catalyst.

Preparation of biocompatible nanocapsules with temperature-responsive and bioreducible properties

Stimuli-responsive biocompatible nanocarriers are very promising for controlled drug release. Here, we report redox- and temperature-responsive biocompatible nanocapsules prepared by growing a temperature-responsive biocompatible shell from 3-(trimethoxysilyl)propyl methacrylate-modified silica nanoparticles (SiO2-MPS) viaprecipitation polymerization, cross-linking the shell with bioreducible chemical linkages, and subsequently removing the silica core by hydrofluoric acid etching. The produced nanocapsules are redox- and temperature-responsive. TEM, FT-IR, TGA, and XPS were used to characterize the nanocapsules. Dynamic light scattering (DLS) was performed to demonstrate the bioreducible and temperature-responsive properties of the nanocapsules. The lower critical solution temperature (LCST) of the nanocapsules can be tuned precisely. Fluorescein isothiocyanate (FITC) was encapsulated into the nanocapsules and used as a model drug molecule to demonstrate the controlled release behavior under external stimuli.

Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery

Intracellular processes, including endosomal escape and intracellular release, are efficiency-determining steps in achieving successful gene delivery. It has been found that the presence of acid-labile units in polymers can facilitate endosomal escape and that the presence of reducible units in polymers can lead to intracellular release. In this study, poly(amido amine)s with both bioreducible and acid-labile properties were synthesized to improve gene delivery compared with single-responsive carriers. Transfection and cytotoxicity were evaluated in three cell lines. The complexes of DNA with dual-responsive polymers showed higher gene transfection efficiency than single-responsive polymers and polyethylenimine. At the same time, these polymers were tens of times less cytotoxic than polyethylenimine. Therefore, a polymer that is both reducible and acid-labile is a promising material for efficient and biocompatible gene delivery.

A new method to cross-link a polyplex for enhancing in vivo stability and transfection efficiency

Disulfide-exchange was found to cross-link the polyplex of disulfide-containing poly(amido amine) and pDNA with heating of the polyplex solution over a short time. The cross-linked polyplexes based on disulfide-containing poly(amido amine) have excellent stability under physiological salt conditions, and have significantly enhanced transfection activity in the serum media compared to non-cross-linked polyplexes. In vivo, ICR mice were injected with the polyplex through the tail vein, the results show that the transfection efficiency of the cross-linked polyplex is higher than that of the non-cross-linked variety. Furthermore, the polyplex containing Cy5 labelled DNA was also injected into the mice to illustrate the stability and distribution of the polyplex, cross-linked polyplexes show a much brighter luminescence than the non-cross-linked ones. This method does not need a cross-linker or catalyst, and there are no impurities produced, it may be an elegant approach to resolve the dilemma of in vivo application of a DNA polyplex, with excellent stability whilst in circulation and a rapid unpacking of the polyplex inside the cells.

Selectively grafting polymer from the interior and/or exterior surfaces of bioreducible and temperature-responsive nanocapsules

A novel strategy is reported for selectively grafting polymer brushes from the interior and/or exterior surfaces of bioreducible and temperature-responsive nanocapsules. Poly(N-isopropylacrylamide-co-poly(ethylene glycol) methacrylate) (P(NIPAM-co-PEGMA)) nanocapsules with hydroxyl groups at the interior surface, exterior surface or both surfaces were first prepared via seeded precipitation copolymerization of N-isopropylacrylamide and poly(ethylene glycol) methacrylate using N,N′-cystaminebisacrylamide (CBA) as the shell crosslinker, respectively. The location of hydroxyl groups at the interior surface or exterior surface or both surfaces was controlled via the addition time of poly(ethylene glycol) methacrylate (PEGMA). Then, Ce4+/mediated redox initiated polymerization was used to graft poly(2-(dimethylamino)ethyl acrylate) (PDMAEA) brushes from the surfaces of P(NIPAM-co-PEGMA) nanocapsules with the selectivity of the grafting position (the interior and/or exterior surfaces) being controlled via hydroxyl location. The resulting nanocapsules are temperature, pH and redox responsive.

Stimuli-Triggered Growth and Removal of a Bioreducible Nanoshell on Nanoparticles

A new and easy method of stimuli-triggered growth and removal of a bioreducible nanoshell on nanoparticles is reported. The results show that pH or temperature could induce the aggregation of disulfide-contained branched polymers at the surface of nanoparticles; subsequently, the aggregated polymers could undergo intermolecular disulfide exchange to cross-link the aggregated polymers, forming a bioreducible polymer shell around nanoparticles. When these nanoparticles with a polymer shell are treated with glutathione (GSH) or d,l-dithiothreitol (DTT), the polymer shell could be easily removed from the nanoparticles. The potential application of this method is demonstrated by easily growing and removing a bioreducible shell from liposomes, and improvement of in vivo gene transfection activity of liposomes with a bioreducible PEG shell.