Thermal- and pH-Responsive Degradable Polymers

Thermal- and pH-Responsive Degradable Polymer

Bioreducible Gene Delivery Vector Capable of Self-Scavenging the Intracellular-Generated ROS Exhibiting High Gene Transfection

Cationic polymer vectors have received increasing attention for gene delivery in biotechnology over the past 2 decades, but few polymer vectors were used in clinical applications due to their low gene transfection efficacy. One of the major reasons is that the conventional cationic polymers can induce the increasing of intracellular reactive oxygen species (ROS) concentration and oxidative stress, which reduces the gene transfection efficacy. Here, we create a novel class of thioether dendron-branched polymer conjugate and self-assemble this conjugate into bioreducible cationic nanomicelles with disulfide bond connecting the thioether core to the cationic shell. The obtained nanomicelles have a unique ROS self-scavenging ability, thereby dramatically improving gene transfection efficacy

‘Living’ Controlled <i>in Situ</i> Gelling Systems: Thiol−Disulfide Exchange Method toward Tailor-Made Biodegradable Hydrogels

A ‘living’ controlled hydrogel formation method was first reported to create loose and compact in situ biodegradable hydrogels. The method executed under mild reaction conditions can conveniently tailor the hydrogel properties, and it has the potential to develop into a powerful tool for the design, synthesis, and self-assembly of novel tailor-made biomaterials and drug delivery systems

Syntheses of Sequence-Controlled Polymers via Consecutive Multicomponent Reactions

Multicomponent reactions have recently attracted a great deal of attention as they are considered as a powerful tool for constructing sequence-controlled polymers. Although new examples are constantly flourishing in the literature, the process that allows two or more consecutive multicomponent-reactions to react in a single operation for the syntheses of sequence-controlled polymers has not been developed until now. Here, we propose a new strategy combining multicomponent reaction of amine, thiol, and alkene conjugating and multicomponent polymerization of diyne, azide, and diamine coupling in one-pot for the synthesis of sequence-controlled polymer

Thermal Control over the Topology of Cleavable Polymers: From Linear to Hyperbranched Structures

We found that the topology of cleavable polymer from linear to hyperbranched can be tuned simply by varying the polymerization temperature:  linear polymers were produced at temperatures ≤ 40 °C, hyperbranched polymers were obtained at elevated temperatures (≥ 48 °C); the degree of branching (DB) of hyperbranched polymers increased with the increase of temperature. Furthermore, the produced linear and hyperbranched polymers contain stimuli-sensitive disulfide bonds in the backbone that can be easily cleaved into small organic molecules in the presence of DTT

A Responsive Hyperbranched Polymer Not Only Can Self-Immolate but Also Can Self-Cross-Link

Though many responsive polymers have been prepared, none of them can both self-immolate and self-cross-link via responding to the changes of the environment. Here, we introduce a new responsive hyperbranched polymer, which not only can self-immolate but also can self-cross-link via responding to the external stimuli. Moreover, the obtained polymer can form a bioreducible nanogel in its aqueous solution simply via heating, and the formed nanogel can self-immolate via UV irradiation

Bioreducible POSS-Cored Star-Shaped Polycation for Efficient Gene Delivery

The bioreducible star-shaped gene vector (POSS-(SS-PDMAEMA)₈) with well-defined structure and relatively narrow molecular weight distribution was synthesized via atom transfer radical polymerization (ATRP) of (2-dimethylamino)­ethyl methacrylate (DMAEMA) from a polyhedral oligomeric silsesquioxane (POSS) macroinitiator. POSS-(SS-PDMAEMA)₈ was composed of a biocompatible POSS core and eight disulfide-linked PDMAEMA arms, wherein the PDMAEMA chain length could be adjusted by controlling polymerization time. POSS-(SS-PDMAEMA)₈ can effectively bind pDNA into uniform nanocomplexes with appropriate particle size and zeta potential. The incorporation of disulfide bridges gave the POSS-(SS-PDMAEMA)₈ material facile bioreducibility. In comparison with POSS-(PDMAEMA)₈ without disulfide linkage, POSS-(SS-PDMAEMA)₈ exhibited much lower cytotoxicity and substantially higher transfection efficiency. The present work would provide useful information for the design of new POSS-based drug/gene carriers

Acid-Labile Poly(glycidyl methacrylate)-Based Star Gene Vectors

It was recently reported that ethanolamine-functionalized poly­(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances