A MOFs/MIPs@GAs Ternary Composite Catalytic System with Graphene Oxide Aerogels as the Multifunctional Skeleton for High-Efficiency Detoxification of Organophosphate Nerve Agents in Pure Water.

Organophosphate nerve agents (OPs) are widely used as pesticides and chemical agents and pose a threat to human health and life. At present, most personal protective equipment usually only serves as physical protection and does not have an effect of chemical detoxification. In this work, ultra lightweight graphene oxide aerogels (GAs) have been used as a multifunctional skeleton to integrate the metal-organic frameworks (MOFs) and molecularly imprinted polymers (MIPs) together for obtaining a high-performance hybrid material (MOFs/MIPs@GAs) on hydrolysis detoxification of OPs.

Tet1 peptide and zinc (II)-adenine multifunctional module functionalized polycations as efficient siRNA carriers for Parkinson's disease.

A bioreducible Zn (II)-adenine multifunctional module (BS) and Tet1 peptide were used to modify low-molecular-weight PEI (polyethyleneimine with molecular weight of 3.5 kDa)into a siRNA vector Zn-PB-T with high transfection efficiency in neurons. A GSH-responsive breakable disulfide spacer was introduced into BS to realize the controlled release of siRNA from the polyplexes in cytoplasm.

Zinc(II)-Quinoline module and ROS cleavable crosslinker functionalized self-fluorescent siRNA vectors for selective gene silencing of cancer cells.

A highly efficient siRNA vector (Zn-PQD) capable of selectively silencing genes in cancer cells was obtained by using ROS-cleavable DED to crosslink low molecular weight (LMW) polyethylene imine (PEI) modified by self-fluorescent metal coordinatied multifunctional module Zn-QS. Under the combined action of DED cross-linking and Zn-QS modification, Zn-PQD performs well in the siRNA delivery process in cancer cells, including siRNA condensation, cell uptake, endosome escape, and siRNA release. Zn-PQD exhibited higher transfection efficiency than commercial PEI and Lipo in multiple cancer cell lines including HepG2, HeLa, 4 T1, H520 and PANC-1, as well as cancer treatment-related stem cell rADSC.

Molecularly imprinted self-buffering double network hydrogel containing bi-amidoxime functional groups for the rapid hydrolysis of organophosphates.

The development of high-performance catalyst materials with high catalytic activity for the hydrolysis of organophosphorus toxicants without additional pH buffer conditions has become an urgent need for practical application. Here, a multifunctional molecularly imprinted polymer double network hydrogel (MIP-DN) material has been prepared by integrating the first polymer network containing the functional group of bi-amidoxime as the catalytic active center and the cationic polymer polyethyleneimine (PEI) with pH buffer function as the main component of the second network. Advantageously, the resultant MIP-DN hydrogel showed excellent catalytic performance without additional pH buffer conditions, exhibiting a half-life of 25 min for the hydrolysis of paraoxon in pure water.

Zinc(II)-Cyclen Multifunctional Complex Module-Mediated Polycation-Based High-Performance pDNA Vectors.

A kind of novel multifunctional modules based on zinc(II)-coordinative cyclen has been developed, which is utilized to modify low molecular weight polyethylenimine (LMWPEI) obtaining high-performance DNA vectors. A series of experiments were carried out to explore the performance of the module in improving the key process of gene transfection, such as DNA condensation, serum resistance, cellular uptake, and endosomal escape. The results demonstrate that there is a significant synergistic effect between the functional module and PEI2.

Zinc(II)-Dipicolylamine Analogs Mediated PEI1.8k/pDNA Vector: Effect of Ligand Structure on the Gene Transport Process.

Zinc ion complexes of dipicolylamine analogs, due to the strong synergistic effect between the Zn complex of containing polypyridine derivatives and polycations in each key step of pDNA transport, have been used as the third component to mediate polyethyleneimine with molecular weight 1.8 kDa (PEI1.8k)/DNA gene delivery system.

Zn(ii)-Dipicolylamine analogues with amphiphilic side chains endow low molecular weight PEI with high transfection performance.

To investigate the effect of amphiphilic balance of Zn(ii)-dipicolylamine analogues on the transfection process, we fabricated a series of Zn(ii)-dipicolylamine functional modules (DDAC-Rs) with different hydrophilic-phobic side chains to modify low molecular weight PEI (Zn-DP-Rs) by the Michael addition reaction. Zn-DP-Rs with hydrophilic terminal hydroxy group side chains demonstrate superior overall performance compared to those of hydrophobic alkyl side chains. In terms of the influence of the chain lengths in DDAC-Rs, from Zn-DP-A/OH-3 to Zn-DP-A/OH-5, the corresponding transfection efficiency shows an upward trend as the lengths increase.

Highly branched poly(β-amino ester) delivery of minicircle DNA for transfection of neurodegenerative disease related cells.

Current therapies for most neurodegenerative disorders are only symptomatic in nature and do not change the course of the disease. Gene therapy plays an important role in disease modifying therapeutic strategies. Herein, we have designed and optimized a series of highly branched poly(β-amino ester)s (HPAEs) containing biodegradable disulfide units in the HPAE backbone (HPAESS) and guanidine moieties (HPAESG) at the extremities.

Multifunctional oligomer immobilized on quartz crystal microbalance: a facile and stabilized molecular imprinting strategy for glycoprotein detection.

Glycoprotein detection holds great potential for early diagnosis of diverse diseases. For this purpose, the combination of quartz crystal microbalance (QCM) sensor and molecular imprinting has attracted increasing attention. Nonetheless, the recently common imprinted films fabricated on QCM electrode are thick and rigid, lacking flexibility in aqueous phase.

Zinc Coordinated Cationic Polymers Break Up the Paradox between Low Molecular Weight and High Transfection Efficacy.

Cationic polymers have emerged as appealing nonviral gene vectors for decades, which, however, suffer from the paradox between low molecular weight and high transfection efficacy. Low molecular weight cationic polymers (LCPs) are well cell tolerated but are perplexed by orders-of-magnitude less efficacy compared to their macromolecular counterparts. The deficiency mainly lies in weak DNA binding of polymers and difficulty in endosomal escape of formulated polyplexes.

Zinc Coordination Substitute Amine: A Noncationic Platform for Efficient and Safe Gene Delivery.

Amines have been extensively involved in vector design thus far, however, their clinical translation has been impeded by several obstacles: cytotoxicity, polyplex serum instability and low efficacy in vivo. In pursuit of functional groups to substitute amines in vector design to address these disadvantages is of great significance. Herein, we report well-tailored noncationic copolymers that contain hydrophilic, hydrophobic, and zinc coordinative moieties through reversible addition-fragmentation chain transfer (RAFT) polymerization for efficient and safe gene delivery.

Virus Spike and Membrane-Lytic Mimicking Nanoparticles for High Cell Binding and Superior Endosomal Escape.

Virus-inspired mimics for gene therapy have attracted increasing attention because viral vectors show robust efficacy owing to the highly infectious nature and efficient endosomal escape. Nonetheless, until now, synthetic materials have failed to achieve high "infectivity," and especially, the mimicking of virus spikes for "infection" is underappreciated. Herein, a virus spike mimic by a zinc (Zn) coordinative ligand that shows high affinity toward phosphate-rich cell membranes is reported.

Alkylated branched poly(β-amino esters) demonstrate strong DNA encapsulation, high nanoparticle stability and robust gene transfection efficacy.

A branched poly(β-amino ester) with numerous alkyl chains (BPA) is designed and synthesized as a safe and efficient non-viral vector. The branching and hydrophobicity synergistically endow BPA with tight DNA condensation, high polyplex stability in serum, high cellular uptake and ultimately robust gene transfection efficiency, largely superior to its linear counterpart (LPA). Our results demonstrate that branching matters for gene delivery by hydrophobic gene vectors.

Biodegradable Highly Branched Poly(β-Amino Ester)s for Targeted Cancer Cell Gene Transfection.

To enhance the gene transfection efficiency to targeted cells while reducing the side effects to untargeted cells is of great significance for clinical gene therapy. Here, biodegradable highly branched poly(β-amino ester)s (HPAESS) are synthesized and functionalized with folate (HPAESS-FA) and lactobionic acid (HPAESS-Lac) for targeted cancer cell gene transfection. Results show that because of the triggered degradability of the vector and enhanced receptor-mediated cellular uptake of polyplexes, the HPAESS-FA and HPAESS-Lac exhibit superior gene transfection capability in specific cancer cells with negligible cytotoxicity, pointing to their promise as targeted vectors for efficient cancer gene therapy.

Bioreducible Zinc(II)-Coordinative Polyethylenimine with Low Molecular Weight for Robust Gene Delivery of Primary and Stem Cells.

To transform common low-molecular-weight (LMW) cationic polymers, such as polyethylenimine (PEI), to highly efficient gene vectors would be of great significance but remains challenging. Because LMW cationic polymers perform far less efficiently than their high-molecular-weight counterparts, mainly due to weaker nucleic acid encapsulation, herein we report the design and synthesis of a dipicolylamine-based disulfide-containing zinc(II) coordinative module (Zn-DDAC), which is used to functionalize LMW PEI (M ≈ 1800 Da) to give a non-viral vector (Zn-PD) with high efficiency and safety in primary and stem cells. Given its high phosphate binding affinity, Zn-DDAC can significantly promote the DNA packaging functionality of PEI and improve the cellular uptake of formulated polyplexes, which is particularly critical for hard-to-transfect cell types.

Multifunctional oligomer incorporation: a potent strategy to enhance the transfection activity of poly(l-lysine).

Natural polycations, such as poly(l-lysine) (PLL) and chitosan (CS), have inherent superiority as non-viral vectors due to their unparalleled biocompatibility and biodegradability. However, the application was constrained by poor transfection efficiency and safety concerns. Since previous modification strategies greatly weakened the inherent advantages of natural polycations, developing a strategy for functional group introduction with broad applicability to enhance the transfection efficiency of natural polycations without compromising their cationic properties is imperative.

N,N,N-trimethylchitosan modified with well defined multifunctional polymer modules used as pDNA delivery vector.

A novel non-viral gene carrier based on N,N,N-trimethylchitosan (TMC) has been fabricated. First, well-defined copolymer P(PEGMA-co-DMAEMA) was synthesized through reversible addition fragmentation chain transfer (RAFT) polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and N,N-(2-dimethylamino)ethyl methacrylamide (DMAEMA). Then allyl group grafting N,N,N-trimethylchitosan (Allyl-TMC) was synthesized via the reaction between allyl bromide and hydroxyl of TMC.

Polycation-Based Ternary Gene Delivery System.

Recent progress in gene therapy has opened the door for various human diseases. The greatest challenge that gene vectors still face is the ability to sufficiently deliver nucleic acid into target cells. To overcome various barriers, plenty of researches have been undertaken utilizing diverse strategies, among which a wide variety of polycation/pDNA vectors have been developed and explored frequently.

Evaluation of the effects of amphiphilic oligomers in PEI based ternary complexes on the improvement of pDNA delivery.

Two kinds of novel oligomers were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization and incorporated into the polyethyleneimine (PEI) gene delivery system through non-electrostatic assembly to improve gene transfection efficiency. The non-electrostatic assembly process was first investigated via probing the interactions of the oligomers with plasmid DNA (pDNA), PEI and AD-293 cells using a quartz crystal microbalance (QCM). The results show that the prepared oligomers almost had no interaction with pDNA while they had much stronger interactions with PEI and AD-293 cells.

A dual-template imprinted capsule with remarkably enhanced catalytic activity for pesticide degradation and elimination simultaneously.

A new strategy of reactant-product-dual-template imprinting incorporated with hollow morphology to improve the catalysis efficiency of microspheres was developed. The synthesized capsule can achieve degradation of the reactant and elimination of its product simultaneously.

Construction of a novel macroporous imprinted biosensor based on quartz crystal microbalance for ribonuclease A detection.

A novel quartz crystal microbalance (QCM) biosensor with high selectivity and sensitivity has been developed for ribonuclease A determination. Macroporous protein imprinted films have been fabricated on the surface of QCM electrode using 2,2,3,4,4,4-hexafluorobutyl methacrylate (HFBMA) as the main matrix monomer, N-methacryloyl-histidine (MAH) as the functional monomer, and trimethylolpropane trimethacrylate (TRIM) as the cross-linker. The imprinted special surface area and the quantity of the imprinted sites were increased by the formation of macropores that were generated by employing calcium carbonate nanoparticles as the porogen.

Gene delivery of PEI incorporating with functional block copolymer via non-covalent assembly strategy.

A novel functional diblock polymer P(PEGMA-b-MAH) is prepared and incorporated to improve the gene delivery efficiency of poly(ethyleneimine) PEI via non-covalent assembly strategy. First, P(PEGMA-b-MAH) is prepared from l-methacrylamidohistidine methyl ester (MAH) by reversible addition fragmentation chain transfer polymerization, with poly[poly(ethylene glycol) methyl ether methacrylate] (P(PEGMA)) as the macroinitiator. Then P(PEGMA-b-MAH) is assembled with plasmid DNA (pDNA) and PEI (M(w)=10kDa) to form PEI/P(PEGMA-b-MAH)/pDNA ternary complexes.

The target gene carrying validity to HePG2 cells with the brush-like glutathione modified chitosan compound.

The grafting modified chitosan with L-glutathione (GSH) end capped PEG brush-like poly [poly(ethylene glycol) methacrylate] (PMPEG), CS-PMPEG-GSH, as the pDNA condensed vector material could result in a much higher transfection efficiency and lower cytotoxity for NIH3T3 cells. In this work, we have further examined the morphology stabilities of CS-PMPEG-GSH/pDNA vectors at different medium pH values and in the presence of serum protein in detail. And then the targeted characters for HepG2 cells have been probed by tracing the cell uptake behavior and transfection efficiency.

4-nitrophenol surface molecularly imprinted polymers based on multiwalled carbon nanotubes for the elimination of paraoxon pollution.

Molecularly imprinted polymers were grafted on the surface of multiwalled carbon nanotubes (MWCNT) using the hydrolysis product of paraoxon 4-nitrophenol as template, 4-vinyl pyridine (4-VPy) as the functional monomer and divinylbenzen (DVB) as the crosslinker. The binding experiments of 4-nitrophenol indicated that the MWCNT based molecularly imprinted polymers (MWCNT-MIP) have much higher adsorption ability than the MWCNT based non-imprinted polymers (MWCNT-NIP). At the same time we found that the adsorption of 4-nitrophenol can help to increase the hydrolytic rate of paraoxon, which indicates that there is an obvious catalyzing effect on the hydrolysis of paraoxon for this kind of materials.