Wen-Jian Zhang

Formation of Hexagonally Packed Hollow Hoops and Morphology Transition in RAFT Ethanol Dispersion Polymerization

Similar to the traditional self-assembly strategy, polymerization induced self-assembly and reorganization (PISR) can produce a myriad of polymeric morphologies through morphology transitions. Besides the chain length ratio (R) of the hydrophobic to the hydrophilic blocks, the chain mobility in the intermediate nano-objects, which is a requisite for morphology transition, is a determining factor in the formation of the final morphology. Although various morphologies have been fabricated, hexagonally packed hollow hoops (HHHs) with highly ordered internal structure have not, to the best of our knowledge, been prepared by PISR. In this article, the fabrication of HHHs through morphology transition from large compound vesicles to HHHs is reported. HHHs with highly regular internal structure may have significance in theoretical research and practical applications of nanomaterials.

Fabrication of Reductive-Responsive Prodrug Nanoparticles with Superior Structural Stability by Polymerization-Induced Self-Assembly and Functional Nanoscopic Platform for Drug Delivery

A highly efficient strategy, polymerization-induced self-assembly (PISA) for fabrication of the polymeric drug delivery systems in cancer chemotherapy is reported. Diblock prodrug copolymer, PEG-b-P(MEO2MA-co-CPTM) was used as the macro-RAFT agent to fabricate prodrug nanoparticles through PISA. The advantages of fabricating intelligent drug delivery system via this approach are as following: (1) Simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation in one-pot at relatively high concentration (100 mg/mL); (2) Almost complete monomer conversion allows direct application of the resultant prodrug nanoparticles without further purification; (3) Robust structures of the resultant prodrug nanoparticles, because the cross-linker was used as the comonomer, resulted in core-cross-linking simultaneously with the formation of the prodrug nanoparticles; (4) The drug content in the resultant prodrug nanoparticles can be accurately modulated just via adjusting the feed molar ratio of MEO2MA/CPTM in the synthesis of PEG-b-P(MEO2MA-co-CPTM). The prodrug nanoparticles with similar diameters but various drug contents were obtained using different prodrug macro-CTA. In consideration of the long-term biological toxicity, the prodrug nanoparticles with higher drug content exhibit more excellent anticancer efficiency due to that lower dosage of them are enough for effectively killing HeLa cells.

Promotion of morphology transition of di-block copolymer nano-objects via RAFT dispersion copolymerization

Reversible addition–fragmentation chain transfer (RAFT) dispersion copolymerization of styrene (St) and methyl methacrylate (MMA) is conducted in methanol using poly(2-hydroxyethyl acrylate) (PHEA) as a macro chain transfer agent (macro-CTA). Compared with the general macro-CTA mediated alcoholic dispersion polymerization of St, RAFT dispersion copolymerization of St and MMA can promote the morphology transition of di-block copolymer nano-objects. Three phase diagrams are constructed by changing the molar ratio of St/MMA to reflect the relationship between the degree of polymerization (DP) of P(St-co-MMA), solids concentration and morphology of obtained nano-materials, and it is found that the phase diagrams could be affected by the molar ratio of St/MMA. Ultra-sensitive differential scanning calorimetry (US-DSC) is employed to determine the glass transition temperature (Tg) of polymeric nano-objects in methanol, and the result shows that the Tg values decrease with the increase of the molar content of MMA units in copolymers. Introduction of MMA units into the solvophobic block can enhance its mobility in methanol, which is beneficial for the morphology transition of di-block copolymer nano-objects.

Fabrication and characterization of silica nanotubes with controlled dimensions

Silica nanotubes with controlled diameters and lengths were fabricated by a template-directed method. Nanowires composed of poly(2-dimethylaminoethyl methacrylate)-block-polystyrene (PDMAEMA–PS), which were fabricated by RAFT dispersion polymerization of styrene in methanol using PDMAEMA as a macro-RAFT agent, were used as sacrificial templates. The diameter of the polymeric nanowires can be adjusted by changing the degree of polymerization (DP) of the hydrophilic PDMAEMA block. As the chain length of the hydrophilic PDMAEMA block increases, the DP of the PS block for formation of the nanowires increases, leading to the diameter increase of the corresponding nanowires. Moreover, the polymeric nanowires with controlled lengths and diameters of the core and the shell can be fabricated on a large scale through polymerization-induced self-assembly and reorganization, conveniently. The weak polyelectrolyte, PDMAEMA shell, is an ideal nanoreactor for deposition of silica to form hybrid nanowires. Silica nanotubes were prepared by calcination of the hybrid nanowires.

Silica Nanotubes Decorated by pH-Responsive Diblock Copolymers for Controlled Drug Release

A novel nanocontainer, which has silica nanotube (SNT) core and pH-sensitive polymer shell attaching on the exterior surface of silica nanotube, is presented in this paper. Polymer nanorods, which are conveniently fabricated though polymerization-induced self-assembly and reorganization method, are used as templates for the deposition of silica to fabricate hybrid nanorods. Calcination of as-synthesized silica hybrid nanorods leads to hollow SNTs. SNTs are functionalized with reversible addition-fragmentation chain transfer (RAFT) agent, then surface RAFT polymerization is conducted to get poly(2-(diethylamino)ethyl methacrylate)-b-poly(oligo(ethylene glycol) methacrylate)-coated SNTs (SNT-PDEAEMA-b-POEGMA). Doxorubicin (DOX) can be encapsulated in SNT-PDEAEMA-b-POEGMA, and controlled release of loaded DOX is achieved by adjusting pH of the medium. In vitro cell viability and cellular internalization study confirm the potential application of this nanocontainer in drug and gene delivery.

Efficient Fabrication of Photosensitive Polymeric Nano-objects via an Ingenious Formulation of RAFT Dispersion Polymerization and Their Application for Drug Delivery

An ingenious formulation of RAFT dispersion polymerization based on photosensitive monomers of 2-nitrobenzyl methacrylate (NBMA) and 7-(2-methacryloyloxy-ethoxy)-4-methyl-coumarin (CMA) is reported herein. Various morphologies, such as spherical micelle, nanoworm, lamella, and vesicle, are fabricated at up to 20% solids content. Photoinduced cleavage of the NBMA moieties and dimerization of the coumarin moieties are simultaneously triggered upon UV (365 nm) irradiation. The former endows the cores of the nano-objects with abundant carboxyl groups, resulting in the transformation of the hydrophobic cores to hydrophilic ones. The latter induces the core-cross-linking of the nano-objects, which endows the nano-objects with enhanced structural stability and prevents the nanoparticle-to-unimer disassembly. The resultant nano-objects exhibit superior structural stability and excellent performances for drug delivery, including high drug loadings, pH-stimuli release, and high-efficient endosomal escape.

A unique fabrication strategy of hierarchical morphologies: combination of multi-step self-assembling and morphology transition

Multi-compartmental cylindrical microstructures with lots of nanotubes on their surface, whose shape resembles a sea cucumber, have been fabricated for the first time. This hierarchical morphology is formed through transitions of vesicles to large compound vesicles, to sea cucumber-like hierarchical microstructures. Along with the morphology transitions, aggregation of the residual polymer chains in the solution occurs, which is called multi-step self-assembling. The driving force of the phase transitions and the multistep self-assembling is polymerization because with the progress of the polymerization, the chain length ratio of PS to P4VP increases, which induces self-assembling and morphology transitions. The requisite for multi-step self-assembling is a high concentration of the P4VP-PS chains remaining in the solution after formation of the nascent assemblies. The concentration of the residual block chains can be controlled by varying the recipe and content of the ethanol. Thus, this study provides a unique strategy to fabricate useful hierarchical assemblies.

Multi-responsive Hyperbranched Star Copolymer: Synthesis, Self-assembly and Controlled Release

Multi-responsive (temperature, pH and redox) hyperbranched star polymers, poly(2-(2-methoxyethoxy)ethyl methacrylate)-star-poly(dimethylaminoethyl methacrylate) (H-PMEO2MA-star-PDMAEMA) have been successfully synthe- sized by self-condensing vinyl polymerization of disulfide-based inimer and MEO2MA first, and subsequently atom transfer radical polymerization of DMAEMA with H-PMEO2MA as macroinitiator. The Mn and Mw/Mn of the H-PMEO2MA were 8300 g/mol and 2.61, respectively. H-PMEO2MA-star-PDMAEMAs with different molecular weights were obtained by ad- justing the polymerization time. The molecular weight of the hyperbranched star copolymer increased but the polydispersity index (PDI) decreased with increasing polymerization time. Since the PDI of the PDMAEMA formed by ATRP is low, with the molecular weight increase of the PDMAEMA, the relative amount of H-PMEO2MA in the hyperbranched star copoly- mers becomes less; as a result, the influence of the core H-PMEO2MAs PDI on the hyperbranched star copolymers de- creases. UV/Vis TU-1901 spectrophotometer was used to investigate the lower critical solution temperature (LCST) of the resultant polymer. The LCST of H-PMEO2MA is relatively low (2—10 ℃). The effects of the compositions and pH of the solution on LCST of the hyperbranched star copolymers were studied. The LCST increased with the chain length increase of PDMAEMA. The pH of the solution has a significant impact on the LCST of the hyperbranched star copolymers. With de- crease of the pH value, the protonation degree of PDMAEMA increased, the repulsion between the chain segments enhanced, making the aggregation of the H-PMEO2MA-star-PDMAEMA molecules become difficult, and as a result, the wa- ter-solubility of the hyperbranched star copolymers enhanced. In addition, when temperature of the aqueous solution raised from 2 ℃ to room temperature, the spherical micelles with H-PMEO2MA as core and PDMAEMA as shell were formed. During the formation of spherical micelles in the aqueous solution of H-PMEO2MA-star-PDMAEMA and Nile Red, the Nile Red was successfully encapsulated in the micelles. The controlled release of this system, in which Nile Red was used as model drug, was investigated, the results showed that this system is pH and redox-responsive, and may have potential appli- cation in drug delivery. Keywords self-condensing vinyl polymerization (SCVP); atom transfer radical polymerization (ATRP); hyperbranched star copolymer; multi-responsive; controlled release

Artificially Smart Vesicles with Superior Structural Stability: Fabrication, Characterizations, and Transmembrane Traffic

Intelligent vesicles are fabricated at up to 30% solid content via an approach of polymerization-induced self-assembly and reorganization (PISR). Upon irradiation with UV light (365 nm), light-triggered dimerization of the coumarin moieties anchored in the membrane leads to the membrane cross-linking of the vesicles, which endows the vesicles with superior structural stability. Due to the tertiary amine groups in the membrane, the vesicles go through a swelling/deswelling change upon switching the pH values. In acidic aqueous solution, the pores in the membrane of vesicles are opened, which is beneficial for transmembrane traffic. The pore size in the membrane of vesicles is in accordance with the extent of membrane cross-linking, which can be conveniently regulated by the irradiation time of UV light (365 nm). The size range of the substance for transmembrane traffic is effectively enlarged; even 15 nm gold nanoparticles can be postloaded into the vesicles with lower extents of the membrane cross-linking through the diffusion method. Although the pores in the vesicle membrane are opened in acidic aqueous solution, transmembrane traffic is inhibited for the electropositive substance because of electrostatic repulsion but is allowed for the electronegative substance. These reported vesicles herein may be the smartest artificial vesicles to date due to their multiple selective permeability.

Polymerization-Induced Self-Assembly of Functionalized Block Copolymer Nanoparticles and Their Application in Drug Delivery

Drug delivery systems (DDS) based on functionalized polymeric nanoparticles have attracted considerable attention. Although great advances have been reported in the past decades, the fabrication efficiency and reproducibility of polymeric nanoparticles are barely satisfactory due to the intrinsic limitations of the traditional self-assembly method, which severely prevent further applications of the intelligent DDS. In the last decade, a new self-assembly method, which is usually called polymerization-induced self-assembly (PISA), has become a powerful strategy for the fabrication of the polymeric nanoparticles with bespoke morphology. The PISA strategy efficiently simplifies the fabrication of polymeric nanoparticles (combination of the polymerization and self-assembly in one pot) and allows the fabrication of polymeric nanoparticles at a relatively high concentration (up to 50 wt%), making it realistic for large-scale production of polymeric nanoparticles. In this review, the developments of PISA-based polymeric nanoparticles for drug delivery are discussed.