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Finding and exploiting safe and high-efficiency gene carriers have always been critical tasks for gene therapy. In this work, novel GSH-triggered degradable organosilica nanoparticles grafted with guanidinated-fluorinated α-polylysine (o-SiNP-GF) are prepared to be studied as gene carriers. The organosilica matrix of o-SiNP-GF is synthesized through the hydrolysis and condensation of 1,2-bis(triethoxysilyl)ethane (BTSE) and bis[3-(triethoxysilyl)propyl]tetrasulfide (BTSPTS). The o-SiNP-GF nanoparticles have a size of about 20 nm. They possess a positive zeta potential of 42 mV in PBS (pH 7.4) and can be disintegrated in the presence of GSH. The cytotoxicity and DNA-binding ability of o-SiNP-GF, as well as in vitro gene transfection performance of DNA/o-SiNP-GF complexes, have been investigated using enhanced green fluorescent protein plasmid (pEGFP) as the DNA model. MTT assay shows that the cytotoxicity of o-SiNP-GF is very low even at a concentration up to 800 μg mL-1. The o-SiNP-GF nanoparticles can effectively bind to pEGFP through a complex coacervation method. The in vitro transfection efficiency of pEGFP/o-SiNP-GF complexes in 293T cells is up to 94.7% at the N/P ratio of 10, much higher than that of pEGFP/PEI complexes. Luciferase gene and fibroblast growth factor (FGF2) gene are also used as the DNA models to study the in vivo gene transfection performance of the o-SiNP-GF carrier by bioluminescence imaging and the evaluation of the healing rate of a mouse wound, respectively. Compared with naked DNA and DNA/PEI complexes, DNA/o-SiNP-GF complexes show much higher in vivo transfection efficiency. This work not only provides a way to prepare novel GSH-triggered degradable organosilica nanoparticles of size less than 50 nm, but also proves that the modification of guanidinated-fluorinated α-polylysine is an effective method to improve the efficiency of gene carriers.

Cyclic polymers have a number of unique physical properties compared with those of their linear counterparts. However, the methods for the synthesis of cyclic polymers are very limited, and some multicyclic polymers are still not accessible now. Here, we found that the five˗membered cyclic structure and electron withdrawing groups make methylene in rhodanine highly active to aldehyde via highly efficient Knoevenagel reaction. Also, rhodanine can act as an initiator for anionic ring-opening polymerization of thiirane to produce cyclic polythioethers. Therefore, rhodanine can serve as both an initiator for ring-opening polymerization and a monomer in Knoevenagel polymerization. Via rhodanine-based Knoevenagel reaction, we can easily incorporate rhodanine moieties in the backbone, side chain, branched chain, etc, and correspondingly could produce cyclic structures in the backbone, side chain, branched chain, etc, via rhodanine˗based anionic ring-opening polymerization. This rhodanine chemistry would provide easy access to a wide variety of complex multicyclic polymers., Cyclic polymers have a number of unique physical properties compared to their linear counterparts but their synthesis is very limited. Here, the authors show a method to form a wide variety of multicyclic polymers by a rhodanine˗based Knoevenagel reaction and ring-opening polymerization.

pH- and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced self-assembly (PISA). First, reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and camptothecin prodrug monomer (CPTM) using biocompatible poly( N -(2-hydroxypropyl) methacrylamide) (PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P(DIPEMA- co -CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate (BzMA) using the PHPMA-P(DIPEMA- co -CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell (PHPMA), the drug-conjugated middle layer (P(DIPEMA- co -CPTM)) and the PBzMA core, and relatively high concentration (250 mg/g). The prodrug nanoparticles can respond to two stimuli (reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin (CPT) within the prodrug nanoparticles could be effectively triggered. pH-Induced hydrophobic/hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.

Clinical success of cancer radiotherapy is usually impeded by a combination of two factors, i.e., insufficient DNA damage and rapid DNA repair during and after treatment, respectively. Existing strategies for optimizing the radiotherapeutic efficacy often focus on only one facet of the issue, which may fail to function in the long term trials. Herein, we report a DNA-dual-targeting approach for enhanced cancer radiotherapy using a hierarchical multiplexing nanodroplet, which can simultaneously promote DNA lesion formation and prevent subsequent DNA damage repair. Specifically, the ultrasmall gold nanoparticles encapsulated in the liquid nanodroplets can concentrate the radiation energy and induce dramatic DNA damage as evidenced by the enhanced formation of γ-H2AX foci as well as in vivo tumor growth inhibition. Additionally, the ultrasound-triggered burst release of oxygen may relieve tumor hypoxia and fix the DNA radical intermediates produced by ionizing radiation, prevent DNA repair, and eventually result in cancer death. Finally, the nanodroplet platform is compatible with fluorescence, ultrasound, and magnetic resonance imaging techniques, allowing for real-time in vivo imaging-guided precision radiotherapy in an EMT-6 tumor model with significantly enhanced treatment efficacy. Our DNA-dual-targeting design of simultaneously enhancing DNA damage and preventing DNA repair presents an innovative strategy to effective cancer radiotherapy.

Stealth coating materials effectively extend a nanoparticle’s systemic circulation lifetime yet limit its cellular internalization, which promotes and prevents tumor targeting, respectively. Here, this contradiction was resolved by using an acutely pH-sensitive zwitterionic stealth ligand capable of responding to small differences in extracellular pH between blood and tumors. Using a photothermal gold nanocage (AuNC) as a model nanotherapeutic, we found that stealth-AuNC nanoparticles showed both significantly enhanced cell uptake efficiency in acidic tumors and a markedly extended systemic circulation lifetime compared to its unaltered analogue. As a result, stealth-AuNC nanoparticles administered intravenously showed significantly enhanced accumulation within the tumor, leading to significantly improved photothermal therapeutic efficacy in mouse models. These results suggests that pH-sensitive zwitterionic ligands with sufficient sensitivity for responding to small differences in extracellular pH between blood and tumors are ideal stealth materials for simultaneously conferring both extended systemic circulation and enhanced cellular internalization, reducing the need for active targeting moieties.

Poly(amidoamine)s (PAMAMs) of high-generations (G > 5) exhibit high efficacy in gene transfection, but their high cost and severe cytotoxicity limit their use in biomedicine. In contrast, PAMAMs of low-generations (G < 3) are less toxic and easy to synthesize, but exhibit low transfection efficacy. In this report, we design a novel amphiphilic dendrimer by conjugating reactive oxygen species (ROS)-responsive poly(propylenesulfide) (PPS) to a low generation PAMAM dendrimer (G = 2, Mw = 3500 Da) via disulfide bonds. This amphiphilic conjugate can self-assemble into stable nanomicelles. The results show that the obtained nanomicelles have a high zeta potential, which can condense DNA tightly. Moreover, the DNA/nanomicelle polyplexes can be fully dissociated by intracellular ROS and easily release the entrapped DNA. As gene vectors, the nanomicelles exhibited high transfection efficacy and fairly low cytotoxicity in vitro.

The development of gene carriers with high delivery efficiency and enough biosafety to replace the current viral vectors and cationic liposomes has long been a key project to achieve the practical application of gene therapy. As an abundant natural polymer, chitosan (CS) possesses incomparably high biocompatibility. However, when it is used as a gene carrier, the gene transfection efficiency is rather disappointing. Herein, we prepared a novel chitosan derivative, poly(tributyl-(4-vinylbenzyl)phosphonium)-grafted CS (CS-P), via γ-ray radiation-induced grafting copolymerization of tributyl-(4-vinylbenzyl)phosphonium in an acidic solution of CS. The CS-P could combine with pEGFP through a complex coacervation method to form pEGFP-loaded CS-P complex particles with a size of about 150 nm and a high positive zeta potential of 41.7 ± 6.1 mV. Agarose gel electrophoresis and an MTT assay show that the pEGFP-loaded CS-P particles have excellent biosafety, superior to pEGFP-loaded unmodified CS particles. In vitro and in vivo gene transfection experiments based on HeLa cells confirmed that pEGFP loaded into CS-P particles exhibits much higher gene transfection efficiency than that loaded into unmodified CS. This work provides not only a new way to modify CS with quaternary phosphonium, but also a useful and feasible way to obtain new CS-based gene vectors with high gene transfection efficiency and biosafety for potentially practical clinic applications.

Chemodynamic therapy based on Fe2+-catalyzed Fenton reaction holds great promise in cancer treatment. However, low-produced hydroxyl radicals in tumor cells constitute its severe challenges because of the fact that Fe2+ with high catalytic activity could be easily oxidized into Fe3+ with low catalytic activity, greatly lowering Fenton reaction efficacy. Here, we codeliver CuS with the iron-containing prodrug into tumor cells. In tumor cells, the overproduced esterase could cleave the phenolic ester bond in the prodrug to release Fe2+, activating Fenton reaction to produce the hydroxyl radical. Meanwhile, CuS could act as a nanocatalyst for continuously catalyzing the regeneration of high-active Fe2+ from low-active Fe3+ to produce enough hydroxyl radicals to efficiently kill tumor cells as well as a photothermal therapy agent for generating hyperthermia for thermal ablation of tumor cells upon NIR irradiation. The results have exhibited that the approach of photothermal therapy nanomaterials boosting transformation of Fe3+ into Fe2+ in tumor cells can highly improve Fenton reaction for efficient chemodynamic therapy. This strategy was demonstrated to have an excellent antitumor activity both in vitro and in vivo, which provides an innovative perspective to Fenton reaction-based chemodynamic therapy.

Micelles have demonstrated an excellent ability to deliver several different types of therapeutic agents, including chemotherapy drugs, proteins, small-interfering RNA and DNA, into tumor cells. Cationic micelles, comprising self-assemblies of amphiphilic cationic polymers, have exhibited tremendous promise with respect to the delivery of therapy genes and gene transfection. To date, research in the field has focused on achieving an enhanced stability of the micellar assembly, prolonged circulation times and controlled release of the gene. This review focuses on the micelles as a nanosized carrier system for gene delivery, the system-related modifications for cytoplasm release, stability and biocompatibility, and clinic trials. In accordance with the development of synthetic chemistry and self-assembly technology, the structures and functionalities of micelles can be precisely controlled, and hence the synthetic micelles not only efficiently condense DNA, but also facilitate DNA endocytosis, endosomal escape, DNA uptake and nuclear transport, resulting in a comparable gene transfection of virus.

Bioreducible polycations, which possess disulfide linkages in the backbone, have emerged as promising nucleic acid delivery carriers due to their high stability in extracellular physiological condition and bioreduction-triggered release of the genetic material. Further benefits of bioreducible polycations include decreased cytotoxicity due to intracellular reducing environment in the cytoplasm that contains high levels of reducing molecules such as glutathione. Here, we describe the synthesis of bioreducible polycations with emphasis on methods to control their topology.

The rapid developments of gene therapy are benefit from the construction of efficient gene vectors, which help therapy genes efficiently overcome the barriers in the transport and transfection. Condensing DNA into nanoparticles is a crucial role in gene transfection, and the electrostatic interactions of synthetic cationic liposomes and cationic polymers with DNA are generally used for condensing DNA. Recent research has shown that the introduction of the hydrophobic interaction, hydrogen bonding, and coordinative interactions to the gene delivery vectors is also very important for DNA condensation, delivery, and transfection. This review focuses on the four types of interactions in condensed DNA nanoparticles, which could provide a new perspective for improving gene transfection efficacy.

Polymeric micelles are promising vehicles for drug delivery these years. The stability of micelles in blood system is very important for the encapsulated therapeutic agents reaching the targeting area. However, generally, micelles are not stable in the presence of proteins and ions after being injected intravenously. The topology of polymer chain on the surface of micelles plays a key role on the stability of micelles. Here we have prepared flower micelles and the traditional micelles via self-assembly of triblock and diblock copolymer of polyethylene glycol (PEG) and poly(e-caprolactone) (PCL) in water. The special PEG shell of flower micelles prevents micelles from ions and proteins, which endows the micelles with the ability to resist aggregation. The experiment results show that flower micelles are much more stable in the presence of serum and salt than traditional micelles, which indicates these micelles would be promising in drug delivery in the future.

Flexible gels have shown great potential in electronic sensors, but their conductivity may decrease or even disappear after long-term or extreme temperature use. Here, a new class of conductive organohydrogel sensors was fabricated with multipurpose adhesion, anti-freezing/drying, excellent humidity-enhanced conductivity, and self-healing properties. By employing the appropriate glycerol/water ratio, the organohydrogel sensor can be used either under low (−30 °C) or high (60 °C) temperature, featuring for catching water from the environment to enhance the conductivity. This work hold promises for the fabrication of high-performance sensing material with multi-functional sensing and synergistic properties.

Reactions combining two or more multicomponent reactions performed sequentially in a single pot have attracted great interest due to the fact that they enable more step- and time economic conversions of simple starting materials into complex targets. However, so far, no such reaction has been applied in the synthesis of topologically different polymers. Here, we first report a novel strategy combining the sequential multicomponent reaction (MCR) of a primary amine, a thiolactone and an alkene and the multicomponent polymerization (MCP) of an azide, an alkyne and a secondary amine in one-pot for the syntheses of topologically different polymers (linear, hyperbranched, core–shell polymers). This strategy provides an effective method that can control the sequence and topology of the obtained polymers simultaneously.

Polycations have high DNA condensing ability, low immunogenicity, and great adaptability, which make them promising for gene delivery. However, low transfection efficiency and inevitable toxicity are challenges of cationic polymers. In this study, we prepared a novel Janus dendritic polymer via a one-step Michael addition reaction of branched low-molecular-weight polyethylenimine (PEI, 1800 Da) and dendritic polythioether. The amphiphilic dendritic polymer can self-assemble into stable nanomicelles with high surface charge potential (+91.8 mV). The obtained nanomicelles can be used as a gene delivery vector, which exhibits a higher gene transfection efficiency and much lower cytotoxicity as compared with gold standard PEI (branched, 25 kDa).

Herein, we report the facile synthesis of a class of well-defined acid-labile polyacetal dendrimers, which can be easily functionalized by poly(ethylene glycol) or zwitterions and self-assemble into pH-responsive degradable micelles or nanofibers.

The reversible coil-to-globule transition of poly(N-isopropylacrylamide) in aqueous solution is a tenet of the physics of polymers. However, most of the studies have been limited on the transition induced only by the variation of hydrogen bonds. How and what the coil structure will develop into are unclear in the presence of other noncovalent bindings besides hydrogen bonds. Here we introduce noncovalent bindings of anion–dipole into poly(N-isopropylacrylamide) aqueous system besides hydrogen bonds and hydrophobic interactions and first have observed that the variant temperature responses of hydrogen bonds and anion–dipole bindings could make the coil structure of poly(N-isopropylacrylamide) unconventionally restructure into micelles, nanorods, vesicles, etc., but not only globule-like structure.

Visible light‐driving syntheses have emerged as a powerful tool for organic synthesis and for the preparation of macromolecules under mild and environmentally benign conditions. However, precious but nonreusable photosensitizers or photocatalysts are often required to activate the reaction, limiting its practicality. Here, it is reported that poly(1,4‐diphenylbutadiyne) (PDPB) nanofibers exhibit remarkable activity in driving the living free radical polymerization under visible light. Moreover, PDPB nanofibers are very stable under irradiation of visible light and can be reused without appreciable loss of activity even after repeated cycling. The nanofiber will be a promising photocatalyst with excellent reusability and stability for the reactions driven by visible light., Polymer nanofibers not only exhibit remarkable activity in driving living free radical polymerization under visible light, but also are very stable under irradiation of visible light and can be reused without appreciable loss of activity even after repeated cycling.

Synthesizing copolymers with controlled, and even precise sequence structures, such as biological macromolecules, has been a serious challenge in polymer science. Recently, hybrid polymerization has become an attention-getting synthetic method for preparing copolymers with different sequence structures. In this review, we will discuss this method and focus on the sequence structure of the obtained copolymers, which have gone through a process from producing random uncontrollable sequences, to constructing sequence-controlled copolymers and even sequence-on-demand copolymers.

The synthesis of polymers with on-demand sequence structures is very important not only for academic researchers but also for industry. However, despite the existing polymerization techniques, it is still difficult to achieve copolymer chains with on-demand sequence structures. Here we report a dually switchable and controlled interconvertible polymerization system; in this system, two distinct orthogonal polymerizations can be selectively switched ON/OFF independent of each other and they can be interconverted promptly and quantitatively according to external stimuli. Thus, the external stimuli can manipulate the insertion of distinct monomers into the resulting copolymer chains temporally, spatially, and orthogonally, allowing the on-demand precise arrangement of sequence structures in the resulting polymers. This dually switchable and interconvertible polymerization system provides a powerful tool for synthesizing materials that are not accessible by other polymerization methods., The synthesis of polymers with on-demand sequence structures is difficult but highly desirable. Here the authors show a dual switchable and controlled interconvertible polymerization involving two orthogonal polymerizations that are switched ON/OFF independent of each other with an external stimulus.

During the last two decades, cationic polymers have become one of the most promising synthetic vectors for gene transfection. However, the weak interactions formed between DNA and cationic polymers result in low transfection efficacy. Furthermore, the polyplexes formed between cationic polymers and DNA generally exhibit poor stability and toxicity because of the large excess of cationic polymer typically required for complete DNA condensation. Herein, we report the preparation of a novel class of bioreducible cationic nanomicelles by the use of disulfide bonds to connect the cationic shell to the fluorocarbon core. These bioreducible nanomicelles form strong interactions with DNA and completely condense DNA at an N/P ratio of 1. The resulting nanomicelle/DNA polyplexes exhibited high biocompatibility and performed very effectively as a gene-delivery system.

Multicomponent polymerizations have become powerful tools for the construction of sequence-defined polymers. Although the Passerini multicomponent reaction has been widely used in the synthesis of sequence-defined polymers, the tandem usage of the Passerini multicomponent reaction and other multicomponent reactions in one-pot for the synthesis of sequence-defined polymers has not been developed until now. In this contribution, we report the tandem usage of the Passerini three-component reaction and the three-component amine-thiol-ene conjugation reaction in one pot for the synthesis of sequence-defined polymers. The Passerini reaction between methacrylic acid, adipaldehyde, and 2-isocyanobutanoate was carried out, affording a new molecule containing two alkene units. Subsequently, an amine and a thiolactone were added to the reaction system, whereupon the three-component amine-thiol-ene conjugating reaction occurred to yield a sequence-defined polymer. This method offers more rapid access to sequence-defined polymers with high molecular diversity and complexity.

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.

Multicomponent reactions are of substantial significance not only for organic synthesis but also for polymer synthesis due to their more bond-forming events per synthetic operation. Generally due to that there are two or more reactions in one multicomponent reaction system, synergistic catalysis, in which the two or more reactions are activated by two or more different catalysts at the same time, is very important for achieving high-efficiency transformations. However, achieving synergistic catalysis via using two or more different catalyst simultaneously is a great challenge. Here, we propose a new reactant-synergistically catalyzed multicomponent reaction, in which the units coming from the reactant can synergistically catalyze the two reactions at the same time. Moreover, this multicomponent reaction can be extended to multicomponent polymerization, which is a very promising method for the preparation of functional polymers with defined-sequence. (C) 2014 Elsevier Ltd. All rights reserved.

Anion-dipole interactions can make homopolymers self-assemble like an amphiphilic block copolymer. Generally, common homopolymers cannot self-assemble into multiple nanostructures. Here, it is reported that anion-dipole interactions can enable a number of homopolymers to achieve a variety of self-assembly behaviors in aqueous solution. Such interactions and self-assembly features have been exclusively reserved for amphiphilic (block) polymers until now.

The morphology controls of formed polymer nanomaterials are very important for developing suitable nanomaterials. Generally, to regulate the assembled morphology of polymers, we should alter the lengths of the block segments, the chemical structures or the selectivity of the solvent. Here, when we added NaSCN into poly(2-(2-(2-methoxyethoxy)ethoxy)ethyl methacrylate) (PMEO3MA) aqueous solution, dipole–anion interactions occurred between the weakly hydrated SCN− anions and the slightly positively charged CHn groups next to the O atoms in the PMEO3MA chain. We used 1H NMR and isothermal titration microcalorimetry (ITC) to confirm the formation of the dipole–anion interactions. Furthermore, TEM and SEM results show that the anion–dipole interactions can regulate the self-assembly of PMEO3MA into nanostructures with different morphologies. A corresponding mechanism is proposed to explain the regulation of the morphology.

Sequential Michael addition-based thiol–ene and free radical mediated thiol–ene reactions for preparing sequence-ordered polymers are reported for the first time. The thiols are produced in situ via the ring-opening of thiolactones, and they can readily react with the electron-deficient carbon–carbon double bond of allyl methacrylate via Michael addition-based thiol–ene, but they are unable to react with the electron-rich carbon–carbon double bond of allyl methacrylate without radicals, and intermediates with thiol and alkene units are formed. After the Michael addition thiol–ene and ring-opening reactions are complete, the thiol is activated by UV irradiation, enabling reaction with the electron-rich carbon–carbon double bond via a free radical-mediated thiol–ene reaction, to form sequence-ordered polymers of high molecular weights.

Human skin exhibits highly nonlinear elastic properties that are essential to its physiological functions. It is soft at low strain but stiff at high strain, thereby protecting internal organs and tissues from mechanical trauma. However, to date, the development of materials to mimic the unique mechanical properties of human skin is still a great challenge. Here we report a bioinspired design of nanostructured elastomers combining two abundant plant-based biopolymers, stiff cellulose and elastic polyisoprene (natural rubber), to mimic the mechanical properties of human skin. The nanostructured elastomers show highly nonlinear mechanical properties closely mimicking that of human skin. Importantly, the mechanical properties of these nanostructured elastomers can be tuned by adjusting cellulose content, providing the opportunity to synthesize materials that mimic the mechanical properties of different types of skins. Given the simplicity, efficiency, and tunability, this design may provide a promising strategy for creating artificial skin for both general mechanical and biomedical applications.

Dendritic–linear–dendritic triblock copolymers have attracted much attention due to their unique topology and special features. However, facile methods are still necessary to synthesize uniform den...

A RAFT/MADIX method can not only copolymerize ethylene with a diverse range of functionally polar monomers, but can also easily tune the polar composition and the polar monomer distribution along the produced copolymer chains. This highly versatile RAFT/MADIX copolymerization platform provides access to a diverse range of polyethylene materials.

A novel PEGylation polypeptide, poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-cysteine) (PEG-PLL-PCys) triblock copolymer is synthesized via the sequential ring-opening polymerization of amino acid N-carboxyanhydrides initiated by methoxypolyethylene glycol amine (mPEG-NH2, Mw is 2 kDa). Subsequently, the obtained polypeptide is partially conjugated with fluorocarbon chains via disulfide exchange reaction. PLL segment can condense plasmid DNA through an electrostatic force to form a complex core, PEG segment surrounding the complex like a corona can prevent the complex from precipitation and reduce the adsorption of serum, while PCys segment with fluorocarbon can enhance the cellular uptake and the stability of the formed polyplex micelles in physiological conditions. Experiment results exhibit that the fluorinated polypeptides have low cytotoxicity and good gene transfection efficiency even in the presence of 50% fetal bovine serum.

A star polymer, β-cyclodextrin-poly(l-lactide) (β-CD-PLLA), and a linear polymer, azobenzene-poly(ethylene glycol) (Azo-PEG), could self-assemble into a supramolecular amphiphilic copolymer (β-CD-PLLA@Azo-PEG) based on the host-guest interaction between β-CD and azobenzene moieties. This linear-star supramolecular amphiphilic copolymer further self-assembled into a variety of morphologies, including sphere-like micelle, carambola-like micelle, naan-like micelle, shuttle-like lamellae, tube-like fiber, and random curled-up lamellae, by tuning the length of hydrophilic or hydrophobic chains. The variation of morphology was closely related to the topological structure and block ratio of the supramolecular amphiphiles. These self-assembly structures could disassemble upon an ultraviolet (UV) light irradiation.

Gold nanocages (AuNCs), which have tunable near-infrared (NIR) absorption and intrinsically high photothermal conversion efficiency, have been actively investigated as photothermal conversion agents for photothermal therapy (PTT). The short blood circulation lifetime of AuNCs, however, limits their tumor uptake and thus in vivo applications. Here we show that such a limitation can be overcome by cloaking AuNCs with red blood cell (RBC) membranes, a natural stealth coating. The fusion of RBC membranes over AuNC surface does not alter the unique porous and hollow structures of AuNCs, and the resulting RBC-membrane-coated AuNCs (RBC-AuNCs) exhibit good colloidal stability. Upon NIR laser irradiation, the RBC-AuNCs demonstrate in vitro photothermal effects and selectively ablate cancerous cells within the irradiation zone as do the pristine biopolymer-stealth-coated AuNCs. Moreover, the RBC-AuNCs exhibit significantly enhanced in vivo blood retention and circulation lifetime compared to the biopolymer-stealth-coated counterparts, as demonstrated using a mouse model. With integrated advantages of photothermal effects from AuNCs and long blood circulation lifetime from RBCs, the RBC-AuNCs demonstrate drastically enhanced tumor uptake when administered systematically, and mice that received PPT cancer treatment modulated by RBC-AuNCs achieve 100% survival over a span of 45 days. Taken together, our results indicate that the long circulating RBC-AuNCs may facilitate the in vivo applications of AuNCs, and the RBC-membrane stealth coating technique may pave the way to improved efficacy of PPT modulated by noble metal nanoparticles.

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.

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.

Photocatalyzed polymerization using organic molecules as catalysts has attracted broad interest because of its easy operation in ambient environments and low toxicity compared with metallic catalysts. In this work, we reported that 4,7-di(thiophen-2-yl)benzo[c][1,2,5]thiadiazole (DTBT) can act as an efficient photoredox catalyst for photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under green light irradiation. Well-defined (co)polymers can be obtained using this technique without any additional additives like noble metals and electron donors or acceptors. The living characteristics of polymerization were verified by kinetic study and the narrow dispersity (Đ) of the produced polymer. Excellent chain-end fidelity was demonstrated through chain extension as well. In addition, this technique showed great potential for various RAFT agents and monomers including acrylates and acrylamides.

Hyperbranched poly(amido amine)s (HPAA) show weak photoluminescence, however, they have shown strong emission after short polyethylene glycol (PEG) chains have been linked onto HPAA macromolecule via Michael addition reaction. These PEGylated hyperbranched poly(amido amine)s show low cytotoxicity and potential application in cell imaging.

Generally, it is very difficult to obtain multistimuli-responsive hydrogel particles. Here, we introduce a novel method for the preparation of multistimuli-responsive hydrogel particles by adding w...

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.

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.

Zhi-Qiang Yu,1 Jun-Jie Yan,1 Ye-Zi You,1,* Qing-Hui Zhou2,*1Chinese Academy of Sciences, Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA*These authors contributed equally to this workAbstract: 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.Keywords: reducible, acid labile, gene delivery, dual-responsive, endosomal escape, intracellular release

Three types of azobenzene-based telechelic guest polymers, PEG-azo, azo-PEG-azo, and PEG-azo4, were synthesized by a facile method. Subsequently, a series supramolecular amphiphiles with three distinct topological structures (hemitelechelic, ditelechelic, and quadritelechelic) were constructed through coupling with host polymer β-cyclodextrin-poly(l-lactide) (β-CD-PLLA) by combined host-guest complexation. Research on the self-assembly behavior of these amphiphiles demonstrated that the variation in self-assembly was tuned by the synergistic interaction of hydrophilicity and the curvature of the polymer chains, and very importantly, the topological structure of amphiphiles demonstrated effective control of the self-assembly behavior.

Functional fluorescent semiconductor quantum dot (QD) based gels prepared via immobilizing QDs in organic matrices have shown promising properties, but the compatibility of QDs and organic matrix is not good, and the interactions of the ligands on the surface of QDs with organic matrix are weak, which lead to poor dispersion of QDs in the formed gel and decrease of photoluminescence after gelation in some cases. In this work, we report a hyperbranched macromolecule that can not only act as an excellent ligand to stabilize QD but also act as a good gelator that can gel QD solution to form a reversible and multiresponsive fluorescent gel. This hyperbranched macromolecule-capped QD is stable, and the sol–gel switching can be easily realized via heating and ultrasonicating. Most important, the formed QD gel shows stronger fluorescence than that of the corresponding solution. This novel QD-hyperbranched macromolecule inorganic/organic hybrid network shows great promise in fields such as imaging, sensors, drug ...

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).

This work presents the novel use of reducible hyperbranched (rHB) polymers for delivery of RNA interference (RNAi) therapeutics. Cationic poly(amido amine) hyperbranched polymers that contain different contents of reducible disulfide to nonreducible linkages (0%, 17%, 25%, and 50%) were used to form interpolyelectrolyte polyplexes with siRNA and precursor miRNA (pre-miRNA). Atomic force microscopy (AFM) revealed rHB complexes of ∼100 nm in size, which exhibited redox-activated disassembly in the presence of dithiothreitol (DTT). The complexes were avidly internalized and showed no cellular toxicity in an endogenous enhanced green fluorescence protein (EGFP) expressing H1299 human lung cancer cell line. The highest specific EGFP gene silencing (∼75%) was achieved with rHB (17%)/siRNA complexes at a weight-to-weight (w/w) ratio of 40 that correlated with the ability for this polymer to successfully transfect pre-miRNA. Evaluation of temporal silencing levels over 72 h revealed incremental knockdown that reached a maximum at 72 h for the rHB (50%) complexes, in contrast to maximum knockdown at 24 h that remained relatively consistent, thereafter, for the rHB (17%), rHB (25%), and non-rHB complexes. The role of particle disassembly for intracellular targeting and modulation of gene silencing addressed in this work are important considerations in the development of this and other next-generation delivery systems.