Synthesis and Thermoresponsive Behaviors of Thermo‑, pH‑, CO₂‑, and Oxidation-Responsive Linear and Cyclic Graft Copolymers

Rational macromolecular design allows us to construct multiresponsive architectural polymers with a potential toward multipurpose applications. This study aims at synthesis and LCST-type thermoresponsive behaviors of multisensitive linear and cyclic graft copolymers with polyacrylamide backbone and hydrophilic PEG grafts. The cloud point could be tuned by many factors, and the effect of cyclization was confirmed by the elevated cloud point in H₂O up to 12.8 °C under same conditions. The PEG-connecting Y junctions with dual amide, thioether, and tertiary amine groups allowed thermo-, solvent-, pH-, and CO₂-switchable inter/intramolecular hydrogen bonding interactions and hence resulted in unusual solvent (H₂O or D₂O) and pH (about 6.8–8.5) dependent phase transition and irreversible CO₂-responsive behavior. Meanwhile, the solution blending could lead to one or two phase transition(s) dependent on types and compositions of the blends. The meticulous introduction of multifunctional Y junctions into graft copolymers offers a versatile route to adjust multitunable thermoresponsive properties

Precise Synthesis of ABCDE Star Quintopolymers by Combination of Controlled Polymerization and Azide–Alkyne Cycloaddition Reaction

A facile approach based on integrated utilization of ring-opening polymerization (ROP), reversible addition–fragmentation chain transfer (RAFT) process, and azide–alkyne cycloaddition reaction was efficiently used to construct amphiphilic 5-arm ABCDE star quintopolymers. The miktoarm stars are composed of poly­(ethylene glycol) (A), poly­(ε-caprolactone) (B), polystyrene (C), poly­(l-lactide) (D), poly­(<i><i>N,N</i></i>-dimethylaminoethyl methacrylate) (E₁), poly­(methyl methacrylate) (E₂), and poly­(methyl acrylate) (E₃). Alkyne-in-chain-functionalized BC and DE diblock copolymers were synthesized by successive ROP and RAFT process. Selective [3 + 2] click reaction between two-azide-end-functionalized PEG and BC copolymer gave azide-core-functionalized ABC star terpolymer, and a subsequent click reaction with DE copolymer afforded well-defined ABCDE stars with well-controlled molecular weight, low polydispersity, and precise composition, as evidenced from ¹H NMR, GPC, and GPC-MALLS analyses. DSC analyses revealed part of polymer segments in ABCDE stars were compatible. This general methodology has some advantages such as straightforward synthesis, mild reaction conditions, versatile polymerizable monomers, and high yields, which is promising for the construction of numerous functional star copolymers with multiple compositions and precise microstructures

One-Pot Controlled Synthesis of Homopolymers and Diblock Copolymers Grafted Graphene Oxide Using Couplable RAFT Agents

An original strategy is presented to synthesize homopolymers and diblock copolymers grafted graphene oxide by simultaneous coupling reaction and RAFT process. Z-functionalized <i>S</i>-methoxycarbonylphenylmethyl <i>S′</i>-3-(trimethoxysilyl)­propyltrithiocarbonate (MPTT) and R-functionalized <i>S</i>-4-(trimethoxysilyl)­benzyl <i>S′</i>-propyltrithiocarbonate (TBPT) were used as couplable RAFT agents to prepare the target nanocomposites. Under similar conditions, MPTT-mediated grafting reaction was liable to afford grafted chains with shorter chain length, narrower molecular weight distribution and lower grafting density than TBPT-based reaction owing to increased shielding effect and different grafting process. The grafted polymers had nearly controlled molecular weight and polydispersity ranging between 1.11 and 1.38, and the apparent molar grafting ratio was estimated to be 73.6–220 μmol/g as the molecular weights of grafted polymers were in the range of 3980–12500 g/mol. The improved solubility and dispersibility of GO–polymer composites in various solvents comprising hexane and water confirmed their amphiphilicity. The grafting process offers an opportunity to alter GO morphologies, and surface morphologies involving nanosheets, nanoparticles, and nanorods were observed as the composites were dispersed in different solvents with the aid of sonication treatment. This tandem approach is promising for surface modification of solid substrates with hydroxyl surface due to its mild conditions, straightforward synthesis and good controllability

Synthesis and Properties of Multicleavable Amphiphilic Dendritic Comblike and Toothbrushlike Copolymers Comprising Alternating PEG and PCL Grafts

Facile construction of novel functional dendritic copolymers by combination of self-condensing vinyl polymerization, sequence-controlled copolymerization and RAFT process was presented. RAFT copolymerization of a disulfide-linked polymerizable RAFT agent and equimolar feed ratio of styrenic and maleimidic macromonomers afforded multicleavable A_<i>m</i>B_<i>n</i> dendritic comblike copolymers with alternating PEG (A) and PCL (B) grafts, and a subsequent chain extension polymerization of styrene, <i>tert</i>-butyl acrylate, methyl methacrylate, and <i>N</i>-isopropylacrylamide gave A_<i>m</i>B_<i>n</i>C_<i>o</i> dendritic toothbrushlike copolymers. (PEG)_<i>m</i>(PCL)_<i>n</i> copolymers obtained were of adjustable molecular weight, relatively low polydispersity (PDI = 1.10–1.32), variable CTA functionality (<i>f</i>_CTA = 4.3–7.5), and similar segment numbers of PEG and PCL grafts, evident from ¹H NMR and GPC-MALLS analyses. Their branched architecture was confirmed by (a) reduction-triggered degradation, (b) decreased intrinsic viscosities and Mark–Houwink–Sakurada exponent than their “linear” analogue, and (c) lowered glass transition and melting temperatures and broadened melting range as compared with normal A_<i>m</i>B_<i>n</i> comblike copolymer. In vitro drug release results revealed that the drug release kinetics of the disulfide-linked A_<i>m</i>B_<i>n</i> copolymer aggregates was significantly affected by macromolecular architecture, end group and reductive stimulus. These stimuli-responsive and biodegradable dendritic copolymer aggregates had a great potential as controlled delivery vehicles

Versatile Synthesis of Multiarm and Miktoarm Star Polymers with a Branched Core by Combination of Menschutkin Reaction and Controlled Polymerization

Menschutkin reaction and controlled polymerization were combined to construct three types of star polymers with a branched core. Branched PVD was synthesized by reversible addition–fragmentation chain transfer (RAFT) copolymerization and used as a core reagent to synthesize multiarm and miktoarm stars with poly­(ε-caprolactone) (PCL), polystyrene, poly­(methyl methacrylate), poly­(<i>tert</i>-butyl acrylate), and poly­(<i>N</i>-isopropylacrylamide) segments. Effects of reaction time, feed ratio, and arm length on coupling reaction between PVD and bromide-functionalized polymer were investigated, and a variety of A_<i>m</i>-type stars (<i>m</i> ≈ 7.0–35.1) were obtained. Meanwhile, A_<i>m</i>B_<i>n</i> stars (<i>m</i> ≈ 9.0, <i>n</i> ≈ 6.1–11.3) were achieved by successive Menschutkin reactions, and A_<i>m</i>C_<i>o</i> stars (<i>m</i> ≈ 8.8–9.0, <i>o</i> ≈ 5.0) were generated by tandem quaternization and RAFT processes. Molecular weights of various stars usually agreed well with the theoretical values, and their polydispersity indices were in the range of 1.06–1.24. The arm number, chain length, and chemical composition of star polymers could be roughly adjusted by control over reaction conditions and utilization of alternative methods, revealing the generality and versatility of these approaches. These ion-bearing stars were liable to exhibit solubility different from normal covalently bonded polymers, and the chain relaxation and melting behaviors of polymer segments were strongly dependent on the macromolecular architecture

Rational Design of Multi-Stimuli-Responsive Nanoparticles for Precise Cancer Therapy

Stimuli-responsive nanoparticles with target capacity are of great interest in drug delivery for cancer therapy. However, the challenge is to achieve highly smart release with precise spatiotemporal control for cancer therapy. Herein, we report the preparation and properties of multi-stimuli-responsive nanoparticles through the co-assembly of a 3-arm star quaterpolymer with a near-infrared (NIR) photothermal agent and chemotherapeutic compound. The nanoparticles can exhibit NIR light/pH/reduction–responsive drug release and intracellular drug translocation in cancer cells, which further integrate photoinduced hyperthermia for synergistic anticancer efficiency, thereby leading to tumor ablation without tumor regrowth. Thus, this rational design of nanoparticles with multiple responsiveness represents a versatile strategy to provide smart drug delivery paradigms for cancer therapy

Dually pH/Reduction-Responsive Vesicles for Ultrahigh-Contrast Fluorescence Imaging and Thermo-Chemotherapy-Synergized Tumor Ablation

Smart nanocarriers are of particular interest as nanoscale vehicles of imaging and therapeutic agents in the field of theranostics. Herein, we report dually pH/reduction-responsive terpolymeric vesicles with monodispersive size distribution, which are constructed by assembling acetal- and disulfide-functionalized star terpolymer with near-infrared cyanine dye and anticancer drug. The vesicular nanostructure exhibits multiple theranostic features including on-demand drug releases responding to pH/reduction stimuli, enhanced photothermal conversion efficiency of cyanine dye, and efficient drug translocation from lysosomes to cytoplasma, as well as preferable cellular uptakes and biodistribution. These multiple theranostic features result in ultrahigh-contrast fluorescence imaging and thermo-chemotherapy-synergized tumor ablation. The dually stimuli-responsive vesicles represent a versatile theranostic approach for enhanced cancer imaging and therapy