pH- and temperature-responsive amphiphilic diblock copolymers of 4-vinylpyridine and oligoethyleneglycol methacrylate synthesized by RAFT polymerization

Diblock copolymers of 4-vinylpyridine (4VP) and oligoethyleneglycol methyl ether methacrylate (OEGMA) were synthesized for the first time using RAFT polymerization technique as potential drug delivery systems. Effects of the number of ethylene glycol units in OEGMA, chain length of hydrophobic P4VP block, pH, concentration and temperature on the solution behavior of the copolymers were investigated comprehensively. Copolymer chains formed micelles at pH values higher than 5 whereas unimeric polymers were observed to exist below pH 5, owing to the repulsion between positively charged P4VP blocks. The size of the micelles was dependent on the relative length of blocks, P4VP and POEGMA. Thermo-responsive properties of copolymers were investigated depending on the pH and length of P4VP block. The increase in the length of P4VP block decreased the LCST substantially at pH 7. At pH 3, LCST of copolymers shifted to higher temperatures due to the increased interaction of copolymers with water through positively charged P4VP block.     

Synthesis and applications of stimuli-responsive hyperbranched polymers

Benefiting from their responsiveness and adaptability, the stimuli-responsive polymers have been widely investigated and exploited in the various fields, such as environmental monitoring, electronics, photonics, controlled drug delivery, medical imaging and diagnostics. These potential applications have greatly promoted the development of advanced functional materials, and meanwhile set higher requirements for the smart materials in the aspects of the spatial structures, diverse linkages and variable functions. However, the linear functional polymers can not satisfy all the requirements of the multi-dimensional molecular design and acute sensitiveness due to the architectural limitation. Accordingly, stimuli-responsive hyperbranched polymers (HBPs) have been drawing more and more attention in recent years owing to their unique globular void-containing topological structure featured with a large number of terminal functional groups and branches, lower solution or melt viscosity, and better solubility. Therefore, design and synthesis of stimuli-responsive HBPs provide a robust tool for controlling the structure transition and creating the hierarchical sensitivity driven by different triggers. In this review, the developments and recent advances of preparation procedures, performance control and promising applications of various stimuli-responsive HBPs have been comprehensively summarized. Besides, the developing trend of stimuli-responsive HBPs is also discussed. It can be found that stimuli-responsive HBPs with different synthetic strategies and diverse performances have manifested more and more versatile applications.     

Dynamically tunable cell culture platforms for tissue engineering and mechanobiology

Human tissues are sophisticated ensembles of many distinct cell types embedded in the complex, but well-defined, structures of the extracellular matrix (ECM). Dynamic biochemical, physicochemical, and mechano-structural changes in the ECM define and regulate tissue-specific cell behaviors. To recapitulate this complex environment in vitro, dynamic polymer-based biomaterials have emerged as powerful tools to probe and direct active changes in cell function. The rapid evolution of polymerization chemistries, structural modulation, and processing technologies, as well as the incorporation of stimuli-responsiveness, now permit synthetic microenvironments to capture much of the dynamic complexity of native tissue. These platforms are comprised not only of natural polymers chemically and molecularly similar to ECM, but those fully synthetic in origin. Here, we review recent in vitro efforts to mimic the dynamic microenvironment comprising native tissue ECM from the viewpoint of material design. We also discuss how these dynamic polymer-based biomaterials are being used in fundamental cell mechanobiology studies, as well as toward efforts in tissue engineering and regenerative medicine.     

Conjugated rod-coil block copolymers: Synthesis, morphology, photophysical properties, and stimuli-responsive applications

Conjugated rod-coil block copolymers have been accorded great importance since they provide a powerful route towards supramolecular objects with novel architectures, functions and physical properties. This review summarizes recent progress on the synthesis, morphology, optoelectronic properties and applications of such block copolymers. The combination of the precise condensation and living polymerization through the grafting-from or grafting-onto methodology produce various architectures of conjugated rod-coil block copolymers, including rod-coil, coil-rod-coil, rod-coil-coil, and rod-coil-rod. In the following, the relationships between polymer morphologies and photophysical properties in different phases are reviewed, as classified by solution micelles, thin films or bulk samples, polymer brushes and electrospun nanofibers. The effects of the rod/coil ratio and polymer architecture on the morphology and optoelectronic properties are discussed. The control of nanosize domain and the aligned direction of conjugated rods are the key issues for enhancing the optoelectronic device performance. Moreover, novel multifunctional sensory materials based on combining the tunable photophysical properties of the π-conjugated rod and the stimuli-responsive coil are also highlighted. It is believed that conjugated rod-coil block copolymers could spark the future evolution of nanostructured polymers for multifunctional device applications.     

Polymer vesicles: Mechanism,preparation, application,and responsive behavior

Polymer vesicles, also known as polymersomes, are finding increasing applications in biomedical field, including drug delivery, gene therapy, magnetic resonance imaging, theranostics, etc. This is due to their intrinsic hollow nanostructure and compartmentalized domains with diverse functionalities. This review describes recent advances in the design and synthesis of polymer vesicles, including the formation mechanisms, preparation methods, applications and responsive behaviors toward external stimuli. We first present the rational design and synthesis of polymer vesicles based on different polymeric building blocks, followed by an insight into the structure and formation mechanism of polymer vesicles, as well as the recently developed means to determine the exact thickness of the vesicle membrane. Except for responding to traditional stimuli such as pH, temperature and oxidation/reduction, polymer vesicles are becoming ‘smarter’ owing to the newly developed stimuli including electrical field, magnetic field, sugar molecules, gas, ultrasound, etc. Finally, the potential applications of polymer vesicles beyond biomedical field are highlighted as novel nanoreactors, water remediation materials, etc.     

Programmed morphing of liquid crystal networks

A promising candidate for the development of stimuli-responsive morphing materials are based on liquid crystal polymer networks. These anisotropic materials will contract along the alignment director and expand perpendicular to it when subjected to an anisotropy-reducing stimulus, such as heat. As the liquid crystals can be aligned prior to polymerization using various alignment techniques, it is possible to create networks with programmed, complex director profiles in three dimensions. This review shows the various designs that can be implemented and the complex morphing behavior that can be achieved in liquid crystal polymer networks.     

Synthesis and characterization of poly(styrene-co-fluorescein O-methacrylate)/poly(N-isopropylacrylamide)-Fe3O4 core/shell composite particles

We demonstrate the synthesis and characteristics of multifunctional poly(styrene-co-fluorescein O-methacrylate)/poly(N-isopropylacrylamide)-Fe₃O₄ [P(St/FMA)/PNIPAAm-Fe₃O₄] core/shell composite particles, in which the core consists of fluorescent materials and the shell consists of magnetic and thermo-responsive components. First, core/shell particles consisting of a fluorescent P(St/FMA) core and thermo-responsive PNIPAAm-rich shell were prepared by two-stage shot-growth emulsion polymerization. Next, Fe₃O₄ nanoparticles were immobilized via electrostatic interactions and then covalently linked to the shell via surface coordinated Aphen by a coupling reaction in order to obtain magnetic properties. The morphology of P(St/FMA)/PNIPAAm-Fe₃O₄ composite particles, confirmed by transmission electron microscopy (TEM), reveals that Fe₃O₄ nanoparticles are located in the PNIPAAm shell. The thermo-sensitivity of composite particles to hydrodynamic diameter was confirmed by using dynamic light scattering (DLS). Photoluminescence (PL) spectra indicate that the fluorescence emission intensity of core/shell particles is highly sensitive to the pH of an aqueous medium. The core/shell composite particles exhibited a combination of fluorescent, magnetic, pH and thermo-responsive behavior.     

双端三齿配体基La(Ⅲ)凝胶聚合物合成及性能研究

以1,6-二溴己烷和1,8-二溴辛烷与富含氮单体2,6-二苯并咪唑基-4-羟基吡啶反应制备双端三齿配体1,6-二-(2,6-(二苯并咪唑基)吡啶氧基)己烷和1,8-二-(2,6-(二苯并咪唑基)吡啶氧基)辛烷。两种配体分别与过渡金属离子La(Ⅲ)组装得到具有温度响应性和化学刺激响应的凝胶状聚合物,并具有一定的荧光效应。NMR表征表明成功的制备了单体及配体,应用TG、XRD对聚合物的性能进行测试。刺激响应性实验表明此凝胶聚合物对温度具有可逆的响应性,并对化学试剂甲酸具有化学刺激响应性。光学性能研究表明,在紫外线的照射下,聚合物具有明显的发光现象,最大发射峰都位于419 nm处。     

Stimuli-Responsive Prodrug Chemistries for Cancer Therapy

Prodrugs are pharmacologically inactive, chemically modified derivatives of active drugs, which, following in vivo administration, are converted to the parent drugs through chemical or enzymatic cleavage. The prodrug approach holds tremendous potential to create the enhanced version of an existing pharmacological agent and leverage those improvements to augment the drug molecules′ bioavailability, targeting ability, therapeutic efficacy, safety, and marketability. Especially in cancer therapy, prodrug application has received substantial attention. A prodrug can effectively broaden the therapeutic window of its parent drug by enhancing its release at targeted tumor sites while reducing its access to healthy cells. The spatiotemporally controlled release can be achieved by manipulating the chemical, physical, or biological stimuli present at the targeted tumor site. The critical strategy comprises drug-carrier linkages that respond to physiological or biochemical stimuli in the tumor milieu to yield the active drug form. This review will focus on the recent advancements in the development of various fluorophore-drug conjugates that are widely used for real-time monitoring of drug delivery. The use of different stimuli-cleavable linkers and the mechanisms of linker cleavage will be discussed. Finally, the review will conclude with a critical discussion of the prospects and challenges that might impede the future development of such prodrugs.     

Dendron-polymer hybrid mediated anticancer drug delivery for suppression of mammary cancer

Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity.Here we report a dendronized polymer-doxorubicin(DOX)hybrid(DPDH)with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate(LPDC).The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4.DPDH efficiently enters 4 T1 cells and releases DOX to induce cytotoxicity and apoptosis.Owing to the dendronzied structure,DPDH has a significantly longer blood circulation time than LPDC.DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4 T1 mammary cancer model than LPDC as well as free drug,evidenced from tumor growth inhibition,TUNEL assessment and histological analysis.Biosafety of DPDH is also confirmed from hemolysis,body weight shifts during treatment and pathological analysis.This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.