Weian Zhang

Self-assembly and disassembly of a redox-responsive ferrocene-containing amphiphilic block copolymer for controlled release

Stimuli-responsive block copolymer micelles have recently emerged as promising drug delivery systems with controllable drug release. Herein, we report well-defined redox-responsive ferrocene-containing amphiphilic block copolymers PEG-b-PMAEFc, which were synthesized by the atom transfer radical polymerization (ATRP) of 2-(methacryloyloxy) ethyl ferrocene-carboxylate (MAEFc) using a PEG-based macro-ATRP agent. These block copolymers can self-assemble into various interesting nanostructures in aqueous solution. The self-assembled morphology of amphiphilic block copolymers is influenced by the nature of the common solvents used, the polymer composition and concentration, and the addition of β-cyclodextrin (β-CD) and redox agents (H2O2 and KMnO4), the effects of which were investigated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Furthermore, the redox agent H2O2 can be used to trigger the release of encapsulated cargo (Rhodamine B) in the polymeric nanocarriers. This redox behavior of the amphiphiles could open up an approach for redox-controlled drug delivery systems.

Photocontrolled reversible supramolecular assemblies of a diblock azo-copolymer based on β-cyclodextrin–Azo host–guest inclusion complexation

The double hydrophobic block copolymer, poly[6-(4-(phenyldiazenyl)phenoxy)hexyl acrylate]-b-polystyrene (PAzo-b-PS), was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. This hydrophobic block copolymer can self-assemble into spherical micelles through β-cyclodextrin–azobenzene (β-CD–Azo) host–guest inclusion. Furthermore, the spherical micelles can be dissociated and reassembled by alternating irradiation of UV/visible light. These supramolecular self-assembly and disassembly procedures were studied by dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM) and UV-Vis spectra.

Porphyrin-containing amphiphilic block copolymers for photodynamic therapy

Amphiphilic PNIPAM-b-PTPPC6MA block copolymers were first synthesized using porphyrin-containing monomers. The mono-hydroxylphenyl-triphenylporphyrin photosensitizer, TPP-OH, was modified into a porphyrin monomer, and it was further used to construct the amphiphilic PNIPAM-b-PTPPC6MA block copolymers using RAFT polymerization. PNIPAM-b-PTPPC6MA block copolymers can self-assemble into a plethora of morphologies ranging from spheres to vesicular aggregates and further to a single large vesicle. The PNIPAM-b-PTPPC6MA micelles exhibited a high singlet oxygen quantum yield. Moreover, confocal laser scanning microscopy (CLSM) and flow cytometry analysis confirmed that PNIPAM-b-PTPPC6MA micelles could effectively enhance the internalization rate in MCF-7 cells. According to the MTT assay, PNIPAM-b-PTPPC6MA micelles exhibited low dark toxicity and efficient PDT efficacy towards MCF-7 cells. Thus PNIPAM-b-PTPPC6MA block copolymers have the potential application for photodynamic therapy.

A PEGylated colorimetric and turn-on fluorescent sensor based on BODIPY for Hg(II) detection in water

We herein reported a click strategy to fabricate two kinds of colorimetric and turn-on fluorescent dual-modal mercury sensors (PEG-DMS) based on the styryl BODIPY scaffold attached to a hydrophilic polymer PEG, where the PEG chain could effectively improve the water solubility of these two mercury sensors and mean that their Hg2+ detection could be performed in pure water, while their corresponding small molecular precursor DMS could only detect Hg2+ in the mixed medium with a large amount of organic solvent. It is interesting that PEG-DMS exhibits an excellent spectral response to Hg2+ by inhibiting the intramolecular charge transfer (ICT) effect from the Hg2+ specific ligand, dithia-dioxa-aza cyclopentadecane, to the BODIPY core. Upon addition of Hg2+, a significant fluorescence enhancing property in conjunction with a visible colorimetric change can be observed. These two sensors are highly selective for Hg2+ over other common cations, whereas PEG-DMS1 with one Hg2+ binding ligand exhibits higher sensitivity than PEG-DMS2 with two Hg2+ binding ligands. Additionally, the sensor could be used as a potential imaging reagent for the detection of Hg2+ uptake in HeLa cells as revealed by confocal laser scanning microscopy (CLSM).

Recent advances in organic–inorganic well-defined hybrid polymers using controlled living radical polymerization techniques

Hybrid organic–inorganic materials comprised of well-defined polymers have been widely recognized for a variety of applications due to their extraordinary properties based on the combination of the different building compositions. During the past decades, many kinds of well-defined hybrid polymers with a variety of architectures have been constructed by polymerization in the presence of inorganic compositions, or by the coupling reaction of functional polymers with inorganic nanoparticles. Thus, techniques could be utilized for the preparation of well-defined organic–inorganic hybrid polymers, including controlled living radical polymerizations (CLRP), such as atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer (RAFT) polymerization. Organic–inorganic hybrid polymers based on polyhedral oligomeric silsesquioxane (POSS), poly(dimethylsiloxane) (PDMS), silica nanoparticles, graphene, carbon nanotubes (CNTs) and fullerene will be discussed in this paper.

Photocontrollable release and enhancement of photodynamic therapy based on host–guest supramolecular amphiphiles

A light-controlled porphyrinic photosensitizer release system was developed based on host-guest TPP-Azo/PEG-β-CD supramolecular amphiphiles, which could significantly enhance the efficiency of photodynamic therapy. TPP-Azo was prepared via esterification between TPP and Azo derivatives, and further used to construct supramolecular amphiphiles with PEG-β-CD. TEM images showed that TPP-Azo/PEG-β-CD amphiphiles can self-assemble into spherical micelles, and then disaggregate under irradiation with 365 nm UV light. The phototoxicity and bio-distribution of TPP-Azo/PEG-β-CD micelles against the MCF-7 cell line were also evaluated by MTT assay, flow cytometry and confocal scanning laser microscopy, respectively. According to MTT assay, the IC50 of the spherical micelle was 31.2 μg mL-1, but it became 20.6 μg mL-1 upon pre-irradiation with 365 nm UV light. This shows for the first time that UV light can well stimulate the release of porphyrin photosensitizers and improve the photodynamic therapy efficiency based on the system of host-guest supramolecular amphiphiles.

Redox-responsive supramolecular amphiphiles based on a pillar[5]arene for enhanced photodynamic therapy

Supramolecular amphiphiles based on a pillar[5]arene with enhanced photodynamic therapy have been fabricated. Supramolecular amphiphiles based on host–guest complexation between a poly(ethylene glycol)-functionalized pillar[5]arene (PEG-P[5]A) and a pyridinium-terminated porphyrin derivative bearing a disulfide bond (TPPC6-SS-Py) could self-assemble into spherical micelles in aqueous solution with good colloidal stability as confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Also, PEG-P[5]A/TPPC6-SS-Py micelles exhibited rapid release of porphyrin photosensitizers in a reducing environment. In addition, these micelles demonstrated nearly no toxicity in the dark but a higher photocytotoxicity upon light irradiation evaluated by the MTT assay. Flow cytometry and confocal laser scanning microscopy (CLSM) revealed a more effective cellular uptake property compared with free porphyrin. Therefore, novel reduction-responsive supramolecular amphiphiles with rapid drug release and superior cell internalization ability are constructed, which may provide a platform for drug delivery systems.

One-pot synthesis of POSS-containing alternating copolymers by RAFT polymerization and their microphase-separated nanostructures

The poly(styrene-alt-maleimide isobutyl POSS) (PSMIPOSS) alternating copolymer is one-pot synthesized via reversible addition-fragmentation transfer (RAFT) polymerization. The results show that a POSS-containing alternating copolymer with a high degree of polymerization (DP) and a low polydispersity index (PDI) is successfully constructed by alternating copolymerization of maleimide isobutyl POSS with styrene, and the molecular weight of the PSMIPOSS alternating copolymer can be well controlled by the amount of RAFT agent. Poly(styrene-alt-maleimide isobutyl POSS)-block-polystyrene (PSMIPOSS-b-PS) block copolymers are also one-pot prepared by RAFT polymerization, and their self-assembly behavior in the bulk is investigated by transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS), which exhibit a series of short-range order phase transitions from the POSS sphere, POSS cylinder to lamella structures with the weight fraction of MIPOSS ranging from 13% to 64%. The thermal properties of POSS-containing copolymers are evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), respectively. The results display that MIPOSS units can enhance the thermal properties of copolymers effectively.

A well-defined alternating copolymer based on a salicylaldimine Schiff base for highly sensitive zinc(II) detection and pH sensing in aqueous solution

We herein report a new strategy to fabricate novel well-defined alternating copolymers of poly(VBCDEG-alt-SaAEMI)s which were synthesized via alternating RAFT copolymerization of para-methoxydiethylene glycol-substituted styrenes (VBCDEG) and N-(2-salicylaldehyde-aminoethyl)maleimides (SaAEMI). 1H NMR, 13C NMR, FTIR and GPC results indicate that poly(VBCDEG-alt-SaAEMI) copolymers have well-defined alternating structures and narrow polydispersity (Mw/Mn < 1.35). It is interesting that poly(VBCDEG-alt-SaAEMI) alternating copolymers exhibit an excellent selective fluorescence “OFF–ON” response to Zn2+ by inhibiting the photoinduced electron transfer (PET) effect through copolymerization, while the monomer SaAEMI almost has no fluorescence response to Zn2+ due to the PET process. The sensors based on poly(VBCDEG-alt-SaAEMI) alternating copolymers have very fast response (30 s) to Zn2+, 62-fold fluorescence enhancement in aqueous solution and a detection limit of about 0.25 μM. Additionally, the poly(VBCDEG-alt-SaAEMI) alternating copolymers also show a remarkable green fluorescence “OFF–ON” switch (230∼fold) when the pH turns from 11 to 12, thus these copolymers have potential application in dual-color detection.

A supramolecular approach for fabrication of photo-responsive block-controllable supramolecular polymers

Self-assembly of stimuli-responsive block copolymers in aqueous solution has attracted considerable attention in the past few decades. Herein, we report a supramolecular modular synthetic approach for the fabrication of photo-responsive block-controllable supramolecular polymers (BSPs) based on the assembly of two homopolymers in water. The homopolymers, namely, the polystyrene modified with adamantane and azobenzene as the end groups (Ad–PS–Azo) and poly(ethylene glycol) modified with β-CD (PEG–β-CD), were successfully synthesized via atom transfer radical polymerization (ATRP) and click chemistry, respectively. The supramolecular triblock copolymer (STP) was constructed through host–guest interactions between β-CD and Ad/Azo moieties, and further self-assembled into micelles in aqueous solution, which were investigated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). This well-defined supramolecular triblock copolymer can reversibly disassemble into a supramolecular diblock copolymer (SDP) by alternating irradiation of UV/visible light, which was revealed by TEM, UV-vis and 1H NMR.