Chunlai Tu

Supramolecular Copolymer Micelles Based on the Complementary Multiple Hydrogen Bonds of Nucleobases for Drug Delivery

Novel supramolecular copolymer micelles with stimuli-responsive abilities were successfully prepared through the complementary multiple hydrogen bonds of nucleobases and then applied for rapid intracellular release of drugs. First, both adenine-terminated poly(ε-caprolactone) (PCL-A) and uracil-terminated poly(ethylene glycol) (PEG-U) were synthesized. The supramolecular amphiphilic block copolymers (PCL-A:U-PEG) were formed based on multiple hydrogen bonding interactions between PCL-A and PEG-U. The micelles self-assembled from PCL-A:U-PEG were sufficiently stable in water but prone to fast aggregation in acidic condition due to the dynamic and sensitive nature of noncovalent interactions. The low cytotoxicity of supramolecular copolymer micelles was confirmed by MTT assay against NIH/3T3 normal cells. As a hydrophobic anticancer model drug, doxorubicin (DOX) was encapsulated into these supramolecular copolymer micelles. In vitro release studies demonstrated that the release of DOX from micelles was significantly faster at mildly acid pH of 5.0 compared to physiological pH. MTT assay against HeLa cancer cells showed DOX-loaded micelles had high anticancer efficacy. Hence, these supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases are very promising candidates for rapid controlled release of drugs.

Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging.

A multifunctional pH-sensitive superparamagnetic iron-oxide (SPIO) nanocomposite system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. Small-size SPIO nanoparticles were chemically bonded with antitumor drug doxorubicin (DOX) and biocompatible poly(ethylene glycol) (PEG) through pH-sensitive acylhydrazone linkages, resulting in the formation of SPIO nanocomposites with magnetic targeting and pH-sensitive properties. These DOX-conjugated SPIO nanocomposites exhibited not only good stability in aqueous solution but also high saturation magnetizations. Under an acidic environment, the DOX was quickly released from the SPIO nanocomposites due to the cleavage of pH-sensitive acylhydrazone linkages. With the help of magnetic field, the DOX-conjugated SPIO nanocomposites showed high cellular uptake, indicating their magnetic targeting property. Comparing to free DOX, the DOX-conjugated SPIO nanocomposites showed better antitumor effect under magnetic field. At the same time, the relaxivity value of these SPIO nanocomposites was higher than 146s(-1)mM(-1) Fe, leading to ~4 times enhancement compared to that of free SPIO nanoparticles. As a negative contrast agent, these SPIO nanocomposites illustrated high resolution in MRI diagnosis of tumor-bearing mice. All of these results confirm that these pH-sensitive SPIO nanocomposites are promising hybrid materials for synergistic MRI diagnosis and tumor therapy.

A supramolecular approach to the preparation of charge-tunable dendritic polycations for efficient gene delivery

A facile supramolecular approach for the preparation of charge-tunable dendritic polycations, by a combination of the multi-functionality of dendritic polymers with the dynamic-tunable ability of supramolecular polymers, has been developed. It provides a new strategy for designing and developing efficient gene vectors via noncovalent interactions.

Construction and application of a pH-sensitive nanoreactor via a double-hydrophilic multiarm hyperbranched polymer.

A double-hydrophilic multiarm hyperbranched polymer with a hyperbranched poly(amidoamine) (HPAMAM) core and many poly(ethylene glycol) monomethyl ether (MPEG) arms connected by pH-sensitive acylhydrazone bonds (HPAMAM-g-MPEG) was successfully prepared. Benefiting from the cationic dendritic core and PEGylation shell, the double-hydrophilic multiarm hyperbranched polymer was used as a nanoreactor for CdS quantum dots (CdS QDs) synthesis in aqueous solution. The obtained HPAMAM-g-MPEG and CdS/HPAMAM-g-MPEG nanocomposites were carefully characterized by (1)H NMR, (13)C NMR, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible absorption spectroscopy (UV-vis), fluorescence spectroscopy (FL), dynamic light scattering (DLS), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and electronic dispersive X-ray spectroscopy (EDS) analysis. Both (1)H NMR and fluorescence spectroscopy investigations confirmed that the acylhydrazone linkage between the dendritic core and linear arms was readily broken under acidic condition (pH <5.5). When MPEG arms departed from the HPAMAM core, the fluorescence intensity of CdS/HPAMAM-g-MPEG nanocomposites greatly increased. Such pH-responsive behavior of CdS/HPAMAM-g-MPEG nanocomposites was utilized as an exploration of a novel fluorescence probe in an acidic lysosome exemplified by COS-7 cells.

Role of Branching Architecture on the Glass Transition of Hyperbranched Polyethers

The influence of branching architecture on the glass transition of hyperbranched polyethers has been investigated. For amorphous samples, the glass transition temperature (T(g)) first increases with the degree of branching (DB), passes through a maximum, and then decreases sharply. An attempt is made to explain this by the competition between the junction density and the free volume of terminal units. For the crystalline samples, the crystallization of polymer chains makes the relationship of DB and T(g) more complicated. By the introduction of branching architecture, the crystallization ability of the branched polymer is weakened gradually. When the samples are isothermally crystallized for a long time, the T(g) of polyethers decreases monotonically with DB.

Self-assembled encapsulation systems with pH tunable release property based on reversible covalent bond

Dynamic diblock polymer PS-r-PEG formed via reversible acylhydrazone connection can be used to construct a pH-responsive self-assembled encapsulation system with high stability and sustained-release property, which shows potential in drug delivery.

Construction and application of pH-triggered cleavable hyperbranched polyacylhydrazone for drug delivery

Polymeric drug carriers with high stability during long circulation and triggered degradation after drug release are particularly interesting in drug delivery. Here, a novel pH-triggered backbone-cleavable hyperbranched polyacylhydrazone (HPAH) was successfully prepared through a simple polycondensation of 2,3-butanedione and 1-(2-aminoethyl) piperazine tri-propionylhydrazine. The experimental results showed that the degree of branching (DB) of HPAH was 0.60, and the weight-average molecular weight (Mw) of end-capped HPAH was 4.0 × 103 with a polydipersity index (PDI) of 1.6. 2D DOSY NMR degradation experiments demonstrated that HPAH was stable in neutral conditions while cleavable in acidic environments. Owing to the existence of numerous acylhydrazine terminals, the anticancer drug doxorubicin (DOX) was conjugated to hydrophilic HPAH. The obtained HPAH-DOX conjugate could self-assemble into polymeric micelles with an average diameter of 20 nm, which were stable under physiological pH but cleavable after endocytosis. Cell viability of HPAH, monomers, and degradation products was maintained above 70% over the culture periods, even when the concentration was up to 3 mg mL−1 according to methyl tetrazolium (MTT) assay in NIH/3T3 cell line. Both flow cytometry and confocal laser scanning microscopy (CLSM) confirmed the high cellular uptake of HPAH-DOX. Anti-cancer effect was evaluated in HeLa cell line, and the DOX dose required for 50% cellular growth inhibition was found to be 3.5 μg mL−1 by MTT assay.

Preparation of CdS Nanocrystals within Supramolecular Self-Assembled Nanoreactors and Their Phase Transfer Behavior

A new strategy for the synthesis of CdS nanocrystals (NCs) within supramolecular self-assembly nanoreactors has been described. The self-assembly nanoreactors were readily constructed through the electrostatic interactions and ion pairs between palmitic acid and the terminal amine groups of hyperbranched polymer. In a chloroform/water two-phase system, aqueous Cd (2+) ions were spontaneously encapsulated into the cavities of self-assembly nanoreactors in chloroform. After reaction with S (2-) ions, the CdS NCs with high stability were obtained. By the addition of excess triethylamine, CdS NCs formed in the self-assembly nanoreactors were transferred from organic phase into aqueous phase. After dialysis and rotorary evaporation, aqueous CdS NCs could be redispersed into chloroform solution containing palmitic acid.

Hybrid Polymerization of Vinyl and Hetero-Ring Groups of Glycidyl Methacrylate Resulting in Thermoresponsive Hyperbranched Polymers Displaying a Wide Range of Lower Critical Solution Temperatures

Hybrid polymerization of glycidyl methacrylate (GMA) with potassium hydride (KH) and various oligo(ethylene glycol)s as the initiating system, in which both vinyl polymerization and ring-opening polymerization occur simultaneously, generates hyperbranched poly(ether-ester)s. The reaction process has been followed by an in situ nuclear magnetic resonance technique. The experimental results indicate that both the vinyl and epoxy groups of GMA undergo polymerization, with the reactivity of the latter being much higher than that of the former. Interestingly, the resulting hyperbranched polymers exhibit a sharp phase transition in water at the lower critical solution temperature (LCST). Significantly, the LCST values can be accurately controlled from 0 to 100 degrees C by changing the hydrophilic/hydrophobic balance of GMA and various oligo(ethylene glycol)s or by modification of the precursor polymer through acetylation. This novel stimuli-responsive hyperbranched polymer is a promising candidate for a new generation of commercially viable thermoresponsive polymers following on from the widely used poly(N-isopropylacrylamide) (PNIPAM).

Controlling the Optical Properties of Hyperbranched Conjugated Polyazomethines through Terminal‐Backbone Interactions

A simple approach to tune the optical properties of the hyperbranched conjugated polymers by only adjusting the terminal-backbone interactions has been reported in this article. Hyperbranched conjugated polyazomethines have been successfully prepared by the reaction of tetramine and dialdehyde. Not only varying the monomer feed ratio to change the quantity of terminal amino groups, but also adopting protonation or complexion with proper dopants (SnCl(2) and β-cyclodextrin), can alter the interactions between amino terminals and imine bonds in the backbone. Correspondingly, the optical properties of the resulting hyperbranched polymers are controlled.