To address the poor thermal stability of isohexides while at the same time retain rigidity, we developed a novel bicyclic diol octahydro-2,5-pentalenediol (OPD) from naturally occurring citric acid in this study. Owing to the bicyclic skeleton composed of two fused cyclopentane rings, OPD is supposed to have perfect rigidity but higher thermal stability compared to isohexides. Herein, OPD was first converted to octahydro-2,5-pentalenediol bis(methyl carbonate) (OPBMC) by reacting with dimethyl carbonate. The absolute stereochemistry of OPBMC was investigated by 2D 1H NMR and 13C NMR as well as single crystal X-ray diffraction. By polymerization of OPBMC with several aliphatic diols [1,8-octanediol (A8), 1,10-decanediol (A10), and 1,12-dodeacnediol (A12)] and alicyclic diols [1,4-cyclohexanedimethanol (CHDM), 1,2,2-trimethylcyclopentane-1,3-dimethanol (TCDM), and octahydro-2,5-pentalenediol (OPD)], a series of bio-based copolycarbonates (co-PCs) with intriguing properties were synthesized. NMR spectra revealed that the stereochemistry of OPBMC was preserved after polymerization. Both differential scanning calorimetry and wide-angle X-ray diffraction analyses revealed that co-PCs made from A8, A10, A12, and OPD are semicrystalline, while co-PCs based on CHDM and TCDM are amorphous. A relatively high T5% of 276 °C and outstanding high Tg up to 80.4 °C were detected for fully OPD-based co-PC, confirming the excellent thermal stability and rigidity of OPD. This work addresses some critical needs for high performance polymers such as improving the sustainability of raw materials and achieving both high Tg values and thermal stability.

Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI–PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.

There is an urgent need for developing novel strategies for bacterial detection and inhibition. Herein, a multifunctional nanomaterial based on mesoporous silica nanoparticles (MSNs) is designed, loaded with amoxicillin (AMO), and surface-coated with 1,2-ethanediamine (EDA)-modified polyglycerol methacrylate (PGEDA), cucurbit[7]uril (CB[7]), and tetraphenylethylene carboxylate derivatives (TPE-(COOH)4) by the layer-by-layer (LbL) self-assembly technique. When bacteria contacts with this nanoassembly, the binding of anionic bacterial surface toward the cationic PGEDA layer of this material can reduce or break the interactions between PGEDA layer and TPE-(COOH)4 layer, leading to attenuated TPE-(COOH)4 emission due to the weakening of aggregation-induced emission (AIE) effect. Furthermore, upon adding adamantaneamine (AD), the more stable AD⊂CB[7] complex forms and PGEDA is liberated through competitive replacement, thus leading to the release of AMO and resulting in much higher antibacterial ability of this nanomaterial. This newly designed nanomaterial possesses dual functions of controllable antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, and bacterial detection ability in aqueous media, suggesting that the design of this multifunctional antibacterial material will provide a simple, effective, and rapid way to control the activity of antimicrobial and open up an alternative new avenue for bacterial detection and elimination.Keywords: aggregation-induced emission; antibacterial materials; bacterial detection; controllable antibacterial activity; supramolecular nanoassembly;

Photodynamic therapy (PDT) is an auspicious strategy for cancer therapy by yielding reactive oxygen species (ROS) under light irradiation. Here, we have developed near-infrared (NIR) triggered polymer encapsulated upconversion nanoparticles (UCNPs) based on aggregation-induced emission (AIE) characteristics and mitochondria target ability for PDT. The coated AIE polymer as a photosensitizer can be photoactivated by the up-converted energy of UCNPs upon 980 nm laser irradiation, which could generate ROS efficiently in mitochondria and induce cell apoptosis. Moreover, a “sheddable” poly(ethylene glycol) (PEG) layer was easily conjugated at the surface of NPs. The pH-responsive PEG layer shields the surface positive charges and shows stronger protein-resistance ability. In the acidic tumor environment, PEGylated NPs lose the PEG layer and show the mitochondria-targeting ability by responding to tumor acidity. A cytotoxicity study indicated that these NPs have good biocompatibility in the dark but exert severe cytotoxicity to cancer cells, with only 10% cell viability, upon being irradiated with an NIR laser. The AIE nanoparticles are a good candidate for effective mitochondria targeting photosensitizer for PDT.Keywords: aggregation-induced emission; cancer cells; mitochondria; photodynamic therapy; upconversion nanoparticles;

Ethanolamine (EA)-functionalized poly (glycidyl methacrylate) (PGMA-EA) has been validated by our pioneering studies as a promising material for the manufacture of gene delivery systems. Herein, PGMA-EA was schemed to attach at the terminus of MOF ligands for the construction of a nanoscaled dendritic catiomer. The resulting molecular structure was arranged to possess well-defined flanking secondary amine and hydroxyl groups, which consequently exerted drastic potency in DNA condensation (approximately 100 nm) and provided appreciable colloidal stabilities in the biological milieu. Note that as compared to the commercial gold standard of branched PEI (25 kDa), the proposed catiomer exhibited markedly higher transfection efficiency because of the appreciable cationic dendritic structure and lower cytotoxicity because of rational arrangement of hydroxyl groups. Therefore, the present study encouraged the utility of an MOF-motif in engineering spatial functional and biological functional nanoscaled structures for biomedical applications.

Photodynamic therapy (PDT) has received enormous attention due to its high specificity in eliminating the malignant tumor cells without interposing normal cells, as compared with chemotherapy. In this work, we fabricated mitochondria-targeted NPs using a new AIE cross-linked copolymer (PAIE-TPP) with far red/near-infrared (FR/NIR) subcellular bioimaging ability and a high reactive oxygen species (ROS) quantum yield of 77.9%. Such high efficiency ROS generation is desirable to increase the efficiency of PDT. The PAIE-TPP NPs possess great cytocompatibility but exert severe cytotoxicity to cancer cells with only 4% of cell viability under ultralow-power-intensity (10 mW cm−2) light irradiation. The AIE cross-linked copolymer NPs not only emit bright FR/NIR fluorescence for efficient in vitro subcellular-mitochondrial bioimaging but also generate high ROS for PDT.

A fluorophore displaying aggregation-induced emission was introduced at the terminus of branched polyethylenimine (PEI). The formulated polyplex not only demonstrated an improved safety profile and preserved transfection activity but also importantly indicated that the uncomplexed naked DNA rather than the polyplexes translocated into the nucleus.

The dilemma of poly(ethylene glycol) surface modification (PEGylation) inspired us to develop an intracellularly sheddable PEG palisade for synthetic delivery systems. Here, we attempted to conjugate PEG to polyethylenimine (PEI) through tandem linkages of disulfide-bridge susceptible to cytoplasmic reduction and an azobenzene/cyclodextrin inclusion complex responsive to external photoirradiation. The subsequent investigations revealed that facile PEG detachment could be achieved in endosomes upon photoirradiation, consequently engendering exposure of membrane-disruptive PEI for facilitated endosome escape. The liberated formulation in the cytosol was further subjected to complete PEG detachment relying on disulfide cleavage in the reductive cytosol, thus accelerating dissociation of electrostatically assembled PEI/DNA polyplex to release DNA by means of polyion exchange reaction with intracellularly charged species, ultimately contributing to efficient gene expression.

A series of β-cyclodextrin-conjugated 4-arm poly(ethylene glycol)-poly(lactide-co-glycolide) (4-arm PEG-PLGA) copolymers were synthesized by a ring-opening polymerization of D,L-lactide and glycolide using 4-arm PEG as initiator, and then conjugated with mono(6-ethylenediamine-6-deoxy)-β-cyclodextrin (CDen) or ethylenediamino-bridged bis-β-CD (BCDen). The chemical structures of copolymers were confirmed by 1H-NMR and FTIR spectroscopy. The β-CD-conjugated PEG-PLGA formed stable reverse micelles due to the formation of β-CD and bovine serum albumin (BSA) inclusion complexation, which could accommodate BSA in the organic solvent with improved encapsulation efficiency. Moreover, we demonstrated a one-step approach to construct macroporous protein-containing films using these reverse micelles. The films with ordered pore arrays were directly prepared from reverse micelles. Interestingly, the protein was totally located in the whole matrix except for the pores.

A series of linear and star-shaped amphiphilic polyethylene glycol block polylactide (PEG-b-PLA) and β-cyclodextrin (CD) conjugated PEG-b-PLA (PEG-b-PLA-CD) copolymers were synthesized. Bovine serum albumin (BSA) aqueous solution was emulsified in the copolymer organic solutions to fabricate reverse micelles (RMs), and was then further transferred into ethyl oleate (EO), a pharmaceutically acceptable vehicle, by the RMs. As identified by 1H NMR, the RMs were formed with a hydrophilic core of PEG and CD, covered with a hydrophobic corona of PLA moiety, and were spherical in shape, as observed by a scan electronic microscope. Compared with the PEG-b-PLA RMs, the PEG-b-PLA-CD RMs presented higher encapsulation efficiency. The release of BSA was influenced by the copolymer composition and architecture. BSA stability in the release aqueous phase was confirmed by circular dichroism spectroscopy. The oil-based formulation fabricated from biodegradable copolymers with high drug loading showed a great potential for protein delivery.

Polymeric vesicles constructed from cyclodextrin- and azobenzene-grafted poly(glycidyl methacrylate)s showed excellent stability owing to the multiple host–guest complexation. Upon culturing in Na2S2O4-contained buffer solution, cargo-loaded vesicles disassembled, for potential applications in colon-specific drug delivery.

Although antibiotics have been widely used in clinical applications to treat pathogenic infections at present, the problem of drug-resistance associated with abuse of antibiotics is becoming a potential threat to human beings. We report a biohybrid nanomaterial consisting of antibiotics, enzyme, polymers, hyaluronic acid (HA), and mesoporous silica nanoparticles (MSNs), which exhibits efficient in vitro and in vivo antibacterial activity with good biocompatibility and negligible hemolytic side effect. Herein, biocompatible layer-by-layer (LBL) coated MSNs are designed and crafted to release encapsulated antibiotics, e.g., amoxicillin (AMO), upon triggering with hyaluronidase, produced by various pathogenic Staphylococcus aureus (S. aureus). The LBL coating process comprises lysozyme (Lys), HA, and 1,2-ethanediamine (EDA)-modified polyglycerol methacrylate (PGMA). The Lys and cationic polymers provided multivalent interactions between MSN-Lys-HA-PGMA and bacterial membrane and accordingly immobilized the nanoparticles to facilitate the synergistic effect of these antibacterial agents. Loading process was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and X-ray diffraction spectroscopy (XRD). The minimal inhibition concentration (MIC) of MSN-Lys-HA-PGMA treated to antibiotic resistant bacteria is much lower than that of isodose Lys and AMO. Especially, MSN-Lys-HA-PGMA exhibited good inhibition for pathogens in bacteria-infected wounds in vivo. Therefore, this type of new biohybrid nanomaterials showed great potential as novel antibacterial agents.Keywords: antibacterial materials; biohybrid nanoparticles; cationic polymers; enzyme response; layer-by-layer self-assembly; lysozyme; MSN; synergistic effects

Tetraphenylethene (TPE) derivatives characterized with distinct aggregation-induced-emission, attempted to aggregate with doxorubicin (Dox) to formulate the interior compartment of polymeric nanoparticulate, served as fluorescence resonance energy transfer (FRET) donor to promote emission of acceptor Dox. Accordingly, this FRET formulation allowed identification of Dox in complexed form by detecting FRET. Important insight into the Dox releasing can be subsequently explored by extracting complexed Dox (FRET) from the overall Dox via direct single-photon excitation of Dox. Of note, functional catiomers were used to complex with FRET partners for a template formulation, which was verified to induce pH-responsive release in the targeted subcellular compartment. Hence, this well-defined multifunctional system entitles in situ observation of the drug releasing profile and insight on drug delivery journey from the tip of injection vein to the subcellular organelle of the targeted cells.Keywords: aggregation-induced-emission; FRET; poly(glycerol methacrylate) (PGMA); tetraphenylethene (TPE); tumor target; two-photon excitation

Characteristic aggregation-induced quenching of π-fluorophores imposed substantial hindrance to their utilization in nanomedicine for insight into microscopic intracellular trafficking of therapeutic payload. To address this obstacle, we attempted to introduce a novel aggregation-induced emission (AIE) fluorophore into the cationic polymer, which was further used for formulation of a gene delivery carrier. Note that the selective restriction of the intramolecular rotation of the AIE fluorophore through its covalent bond to the polymer conduced to immense AIE. Furthermore, DNA payload labeled with the appropriate fluorophore as the Förster resonance energy transfer (FRET) acceptor verified a facile strategy to trace intracellular DNA releasing activity relying on the distance limitation requested by FRET (AIE fluorophore as FRET donor). Moreover, the hydrophobic nature of the AIE fluorophore appeared to promote colloidal stability of the constructed formulation. Together with other chemistry functionalization strategies (including endosome escape), the ultimate formulation exerted dramatic gene transfection efficiency. Hence, this report manifested a first nanomedicine platform combining AIE and FRET for microscopic insight into DNA intracellular trafficking activity.Keywords: aggregation-induced emission (AIE); FRET; gene transfection; poly(glycerol methacrylate) (PGMA); tetraphenylethene (TPE); two-photon excitation

In this feature article, we give an overview of the preparation and application of self-assembled architectures based on an emerging area of polymers, i.e., poly(glycidyl methacrylate)s (PGMAs) and their derivatives. A series of PGMA-based aggregates and hybrids, such as micelles, reverse micelles, capsules, nanoparticles, and inorganic–organic hybrid materials, has been constructed, and diverse morphologies were formed, driven by hydrophobic interactions, hydrogen bonding, ionic complexation, host–guest interactions, etc. In particular, the assemblies have shown great potential applications as drug vectors, gene vectors, solubilizing agents, antimicrobial agent, and so forth. Herein, the general guidelines are elaborately selected from literature examples and partially from our own. Although still in its infancy, self-assembly of PGMA-based polymers is expected to become a hot topic in polymer chemistry and materials science.

A new type of reverse vesicle was successfully constructed from pseudo-graft amphiphilic copolymers in dichloromethane, by dint of the host–guest inclusion complexation between β-cyclodextrins and cholesterols. Pseudo-graft copolymers were constructed from β-cyclodextrin conjugated linear or star-shaped poly(glycerol methacrylate)s (PGMAs) of different molecular weights and a cholesterol-ended linear polylactide. The Z-average diameter of reverse vesicles was in the range of 150–350 nm with an ideal narrow polydispersity, and could be tuned by adjusting the molecular weight and branching of backbone PGMAs. Interestingly, these reverse vesicles could be transformed into organogels under specified conditions, i.e. the concentration of reverse vesicles was >1.5 g L−1, and the DCM–H2O ratio (v/v) was 8:1. Extraction of Congo red from the aqueous phase to the organic phase showed good cargo encapsulation capability of reverse vesicles, demonstrating their great potential as carriers or nanoreactors.

A series of amphiphilic polyurethane (PU) copolymers were synthesized by a condensation reaction of poly(ethylene glycol) (PEG) of different molecular weights and 1,6-hexamethylene diisocyanate (HDI), with/without end-capped heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD). Their chemical structures were characterized by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance (1H-NMR) spectroscopy. Their molecular weights, thermal properties and crystallization properties were investigated using gel permeation chromatography (GPC) and differential scanning calorimetry (DSC), respectively. A model protein, bovine serum albumin (BSA), was encapsulated into the PU reverse micelles (RMs) with/without DM-β-CD entities using an emulsification method in dichloromethane (DCM), and then further transferred in biocompatible oil, i.e., ethyl oleate. The diameter of RMs in DCM decreased from 180–480 nm to 100–280 nm upon heating, as determined by dynamic light scattering (DLS), and it was spherical in shape, as observed using a scanning electron microscope (SEM). The encapsulation efficiency (EE) and loading capacity (LC) of BSA in the RMs composed of DM-β-CD-containing PUs were much higher than those without DM-β-CD. In vitro release studies showed that the release rate of RMs of DM-β-CD-containing PUs was faster than their counter parts without DM-β-CD. Interestingly, among all the RMs in the present study, the RMs of DM-β-CD-containing PUs composed of the irregular segments of both PEG1000 and PEG2000 exhibited the highest EE and LC, and the fastest release rate of its cargo. These results highlight the ability of RMs of proper PU composition to act as carriers for protein in an oleous phase with good EE and proper release behavior, paving a new way for the application of PU-based RMs in protein or peptide delivery.

A novel pseudo-graft copolymer was developed for protein delivery, based on the self-assembly of (6-(2-aminoethyl)-amino-6-deoxy)-cyclodextrin (β-CDen)-modified poly(aspartic acid) (PASP-CD) with cholesterol-modified poly(D,L-lactide) (PLA-Chol) by host–guest inclusion complexation. The chemical structures of polymers were confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. These components were then investigated for their ability to form nanoparticles and encapsulate protein. The diameter of micelles in water ranged from 70 to 200 nm as determined by dynamic light scattering, and the micelles were spherical in shape as observed by transmission electron microscopy. A model protein, bovine serum albumin (BSA), was encapsulated into the pseudo-graft copolymer micelles. The encapsulation efficiency (EE) and loading capacity (LC) of BSA in the micelles could be well tuned by adjusting the composition of the pseudo-graft copolymers. The micelles with a lower molar ratio of CD and cholesterol (hydrophilic/hydrophobic) exhibited a higher EE and LC. While in vitro release studies showed that a shorter chain of hydrophobic segment and higher hydrophilic/hydrophobic molar ratio could enhance the release rate. Cell viability studies showed that these materials possessed good cell viability (>95%). These results suggest that the degradable copolymers with appropriate hydrophilic and hydrophobic composition are able to self-assemble into micelles that are an effective and biocompatible vehicle for delivering protein, paving a new way for the application of pseudo-graft copolymers in protein or peptide delivery.

A series of amphiphilic graft copolymers based on biodegradable and biocompatible poly(aspartic acid)s were synthesized by a successive aminolysis reaction of polysuccinimide using octadecylamine/dodecylamine, and ethylenediamine-β-cyclodextrin/ethanediamine. The chemical structures of the copolymers were confirmed by FT-IR and 1H NMR spectroscopy. Large compound reverse micelles consisting of numerous small reverse micelles with polar cores and hydrophobic shells were formed in octanol solution. The reverse micelles showed various particle sizes based on the different length of hydrophobic alkyl chains and molecular weight of polysuccinimide, as determined by dynamic light scattering. Interestingly, the particle size of micelles showed temperature dependence, the diameter decreased continuously with increasing temperature. Their morphology and assembly properties were characterized using scanning electron microscopy, transmission electron microscopy and fluorescence spectroscopy. The reverse micelles were extremely efficient in extracting Congo red from water into octanol, exhibiting a potential application as delivery vehicles in the pharmaceutical and cosmetic fields, and as nanocontainers for separation of inorganic molecules as well.

A series of linear and star-shaped amphiphilic polyethylene glycol block polylactide (PEG-b-PLA) and β-cyclodextrin (CD) conjugated PEG-b-PLA (PEG-b-PLA-CD) copolymers were synthesized. Bovine serum albumin (BSA) aqueous solution was emulsified in the copolymer organic solutions to fabricate reverse micelles (RMs), and was then further transferred into ethyl oleate (EO), a pharmaceutically acceptable vehicle, by the RMs. As identified by 1H NMR, the RMs were formed with a hydrophilic core of PEG and CD, covered with a hydrophobic corona of PLA moiety, and were spherical in shape, as observed by a scan electronic microscope. Compared with the PEG-b-PLA RMs, the PEG-b-PLA-CD RMs presented higher encapsulation efficiency. The release of BSA was influenced by the copolymer composition and architecture. BSA stability in the release aqueous phase was confirmed by circular dichroism spectroscopy. The oil-based formulation fabricated from biodegradable copolymers with high drug loading showed a great potential for protein delivery.

Polymeric vesicles constructed from cyclodextrin- and azobenzene-grafted poly(glycidyl methacrylate)s showed excellent stability owing to the multiple host–guest complexation. Upon culturing in Na2S2O4-contained buffer solution, cargo-loaded vesicles disassembled, for potential applications in colon-specific drug delivery.

In this feature article, we give an overview of the preparation and application of self-assembled architectures based on an emerging area of polymers, i.e., poly(glycidyl methacrylate)s (PGMAs) and their derivatives. A series of PGMA-based aggregates and hybrids, such as micelles, reverse micelles, capsules, nanoparticles, and inorganic–organic hybrid materials, has been constructed, and diverse morphologies were formed, driven by hydrophobic interactions, hydrogen bonding, ionic complexation, host–guest interactions, etc. In particular, the assemblies have shown great potential applications as drug vectors, gene vectors, solubilizing agents, antimicrobial agent, and so forth. Herein, the general guidelines are elaborately selected from literature examples and partially from our own. Although still in its infancy, self-assembly of PGMA-based polymers is expected to become a hot topic in polymer chemistry and materials science.

A fluorophore displaying aggregation-induced emission was introduced at the terminus of branched polyethylenimine (PEI). The formulated polyplex not only demonstrated an improved safety profile and preserved transfection activity but also importantly indicated that the uncomplexed naked DNA rather than the polyplexes translocated into the nucleus.