Block Copolymer Nanoassemblies Research Articles

Dual acid/glutathione-responsive core-degradable/shell-sheddable block copolymer nanoassemblies bearing benzoic imines for enhanced drug release

Development of dual acid/GSH-responsive strategy based on block copolymer nanoassemblies labeled with benzoic imine bonds at core/corona interfaces and disulfide linkages in hydrophobic cores at dual locations for precise control over drug release.

Synthesis and Dual-Acid/Light-Responsive Disassembly of Amphiphilic Block Copolymer Nanoassemblies Bearing Conjugated Benzoic Imine Pendants

Stimuli-responsive degradable amphiphilic block copolymers (SRD-ABPs) have been extensively explored as a promising building block in the construction of smart nanoassemblies exhibiting controlled/enhanced release of encapsulated molecules including therapeutics. Recent advance involves the development of effective approaches to synthesize dual SRD-ABPs and their nanoassemblies, most of which are conventionally designed with two different cleavable linkages (different functional groups), thus responding to two stimuli, typically acid-labile and photoresponsive groups. Herein, we report a new approach to achieve dual acidic pH/light responses with a single labile linkage employing conjugated benzoic imine chemistry. As a proof-of-concept investigation of the approach, a well-defined poly(ethylene glycol)-based SRD-ABP containing conjugated benzoic imine pendants in the hydrophobic block was synthesized by a combination of reversible deactivation radical polymerization and postpolymerization modification. The synthesized copolymer self-assembled in an aqueous solution to form colloidally stable nanoassemblies, consisting of acid/light-degradable hydrophobic core bearing conjugated imine linkages surrounded with hydrophilic coronas. Upon dual responses to acidic pH and UV/visible light, the nanoassemblies degraded through a change in the hydrophobic/hydrophilic balance of micelle cores. This work demonstrates the versatility of a new approach to design and develop advanced nanoassemblies exhibiting dual-acid/light responses on a single conjugated benzoic imine group, thus being effective for intracellular drug delivery.

Topology-Dependent pH-Responsive Actuation and Shape Memory Programming for Biomimetic 4D Printing.

Biomimetic actuators are critical components of bionics research and have found applications in the fields of biomedical devices, soft robotics, and smart biosensors. This paper reports the first study of nanoassembly topology-dependent actuation and shape memory programming in biomimetic 4D printing. Multi-responsive flower-like block copolymer nanoassemblies (vesicles) were utilized as photocurable printing materials for digital light processing (DLP) 4D printing. The flower-like nanoassemblies enhanced thermal stability attributed to their surface loop structures on the shell surfaces. Actuators prepared from these nanoassemblies displayed topology-dependent bending in response to pH and temperature programmable shape memory properties. Biomimetic octopus-like soft actuators were programmed with multiple actuation patterns, large bending angles (∼500 °), excellent weight to lift ratios (∼60), and moderate response time (∼5min). Thus, nanoassembly topology-dependent and shape-programmable intelligent materials were successfully developed for biomimetic 4D printing. This article is protected by copyright. All rights reserved.

Fluorine-Containing Triblock Copolymer Vesicles with Microphase-Separated Structure

Introduction of a fluorine-containing block into block copolymers is an effective method to tune block copolymer nanoassemblies with a microphase-separated structure. However, this microphase-separated structure is difficult to clearly observe due to its nanoscale size. In this work, fluorine-containing ABC triblock copolymer vesicles of poly(ethylene glycol)-block-polystyrene-block-poly(4-vinylbenzyl pentafluorophenyl ether) (PEG-b-PS-b-PVBFP) are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization under dispersed condition. Owing to the choice of a suitable degree of polymerization of the three blocks, the synthesized PEG45-b-PS197-b-PVBFP233 vesicles have a relatively large size of around 216 nm and a thin vesicular membrane with a thickness of around 28 nm. Ascribed to the relatively large size of the vesicles and the thin vesicular membrane, it is concluded that the fluorine-containing PVBFP block forms 9 nm columnar microdomains shielded by the PS phase in the vesicular membrane.

Networking of Block Copolymer Nanoassemblies via Digital Light Processing Four-Dimensional Printing for Programmable Actuation

Controls over stimuli-responsive functional materials and programmable shape deformations are key features in the four-dimensional (4D) printing of soft actuators. Instead of using random copolymers, homopolymers, or natural polymers, this paper reports the first use of amphiphilic, photocurable, and pH-responsive block copolymer (BCP) nanoassemblies in digital light processing (DLP) 4D printing to fabricate smart and programmable soft actuators. Programmable actuation was studied via a bottom-up approach: (1) designed synthesis of pH-responsive BCPs, (2) nanoassembly structures of BCPs, and (3) networking of nanoassemblies via the photocuring process in DLP. As a proof-of-concept, bilayered grippers, ring-shaped actuators, and octopus-like actuators were programmed to produce a range of bending angles and actuation patterns. pH-responsive BCP nanoassemblies were also combined with commercially available three-dimensional printing liquid resin (PlasClear) to produce stimulus-responsive printing ink that was successfully used for 4D printing applications. Thus, smart and programmable materials were developed for 4D printing applications.

Synthesis of Cross-Linked Block Copolymer Nanoassemblies and their Coating Application.

Since the discovery of polymerization-induced self-assembly (PISA), convenient synthesis of concentrated block copolymer nanoassemblies dispersed in solvent has been achieved. Now, application of block copolymer nanoassemblies should be paid more attention. In this study, corona-cross-linked block copolymer nanoparticles of poly[dimethylacrylamide-co-(diacetone acrylamide)]-b-polystyrene [P(DMA-co-DAAM)-b-PS] containing the poly(DAAM) segment in the hydrophilic P(DMA-co-DAAM) block are synthesized initially by PISA following dispersion reversible addition-fragmentation chain transfer polymerization and then by covalent intraparticle cross-linking through the poly(DAAM) segment and adipic acid dihydrazide. Coating application of the corona-cross-linked block copolymer nanoassemblies is tried, and much higher water resistance of the corona-cross-linked block copolymer nanoassemblies than that of the linear block copolymer nanoassemblies is demonstrated.

Cross-linking approaches for block copolymer nano-assemblies via RAFT-mediated polymerization-induced self-assembly

This minireview summarizes the current cross-linking approaches to stabilize block copolymer nano-assemblies obtained via RAFT-mediated PISA process.

Development and disassembly of single and multiple acid-cleavable block copolymer nanoassemblies for drug delivery

Acid-degradable block copolymer-based nanoassemblies are promising intracellular candidates for tumor-targeting drug delivery as they exhibit the enhanced release of encapsulated drugs through their dissociation.

RAFT Dispersion Polymerization in the Presence of Block Copolymer Nanoparticles and Synthesis of Multicomponent Block Copolymer Nanoassemblies

Multicomponent block copolymer nanoassemblies are constructed by two or more than two block copolymers. Herein, multicomponent block copolymer nanoparticles constructed with poly(4-vinylpyridine)-b...

Tumor-targeting intracellular drug delivery based on dual acid/reduction-degradable nanoassemblies with ketal interface and disulfide core locations

Dual acid/reduction-degradable block copolymer nanoassemblies both at core/corona interfaces and in micellar cores leading to synergistic and accelerated drug release for robust tumor-targeting intracellular drug delivery.

Synthesis of star thermoresponsive amphiphilic block copolymer nano-assemblies and the effect of topology on their thermoresponse

Well-defined multi-arm star thermoresponsive block copolymer nano-assemblies of [poly(N-isopropylacrylamide)-block-polystyrene]n [(PNIPAM-b-PS)n] with n = 1, 2, 3 and 4 arms were synthesized by RAFT dispersion polymerization via polymerization-induced self-assembly.

Synthesis of block copolymer nano-assemblies via ICAR ATRP and RAFT dispersion polymerization: how ATRP and RAFT lead to differences

Block copolymer nano-assemblies were synthesized via ICAR ATRP dispersion polymerization employing the CuBr2/tris(2-pyridylmethyl)amine catalyst in an alcoholic solvent at a relatively low temperature of 45 °C.

Disassembly and tumor-targeting drug delivery of reduction-responsive degradable block copolymer nanoassemblies

Review on recent strategies to synthesize novel disulfide-containing reductively-degradable block copolymers and their nanoassemblies as being classified with the number, position, and location of the disulfide linkages toward effective tumor-targeting intracellular drug delivery exhibiting enhanced release of encapsulated drugs.

Star Block Copolymer Nanoassemblies: Block Sequence is All-Important

Star and linear block copolymers of [poly(4-vinylpyridine)-block-polystyrene]n [(P4VP-b-PS)n] and [polystyrene-block-poly(4-vinylpyridine)]n [(PS-b-P4VP)n] (n = 1–4) with similar chemical composition but different block sequence were synthesized by RAFT polymerization. Star (P4VP-b-PS)n is composed of a jointed P4VP core and several outer PS arms, and (PS-b-P4VP)n has just the opposite block sequence and different conformation. The effect of block sequence on the block copolymer nanoassemblies is explored. It is discovered that star (P4VP-b-PS)n tends to form complicated nanoassemblies in the block selective solvent for P4VP due to the PS arms bridging, and star (PS-b-P4VP)n acts somewhat like linear amphiphilic block copolymers. Our study demonstrates the crucial role of block sequence in star block copolymer nanoassemblies.

Synthesis of diblock copolymer nano-assemblies: Comparison between PISA and micellization

RAFT dispersion polymerization following the formulation of polymerization induced self-assembly (PISA) and micellization of pre-prepared amphiphilic block copolymers in block-selective solvents are generally used to prepare block copolymer nano-assemblies. Herein, we make a comparison between these two methods by employing two typical block copolymers of poly(acrylic acid)-block-polystyrene (PAA-b-PS) and poly(ethylene glycol)-block-polystyrene (PEG-b-PS). It is found that the block copolymer nano-assemblies prepared by these two methods are similar with each other when the solvophilic block is relatively long and the solvophobic block is relatively short. Otherwise, the block copolymer nano-assemblies by these two methods are different. The possible reasons leading to the difference between PISA and micellization are discussed, and the kinetic factors including temperature, polymer concentration and solvent are ascribed. It is thought that the present study is helpful to clarify how the kinetic factors beyond the block copolymer itself affecting block copolymer morphology.

Topology Affecting Block Copolymer Nanoassemblies: Linear Block Copolymers versus Star Block Copolymers under PISA Conditions

Linear and star block copolymer (BCP) nanoassemblies of [poly(4-vinylpyridine)-block-polystyrene]n ([P4VP-b-PS]n) with different arm numbers have been synthesized by RAFT dispersion polymerization under formulation of polymerization-induced self-assembly (PISA). All RAFT dispersion polymerizations employing mono- and multifunctional macromolecular chain transfer agents proceed with similar polymerization kinetics. The size and/or morphology of [P4VP-b-PS]n nanoassemblies are firmly correlative to arm number n, and star [P4VP-b-PS]n BCPs have more complex morphology than the linear counterpart. Several interesting morphologies of star BCPs including small-sized vesicles and porous nanospheres have been synthesized, and they are compared with those of the linear counterpart. Our research indicates that topology is a significant parameter to dedicate the size and morphology of star BCP nanoassemblies under PISA conditions.

Influence of Solvophilic Homopolymers on RAFT Polymerization-Induced Self-Assembly

A new method to modulate RAFT dispersion polymerization by introducing solvophilic homopolymers into the polymerization medium is proposed. It is discovered that in RAFT dispersion polymerization employing poly(4-vinylpyridine) trithiocarbonate macro-RAFT agent, the introduced solvophilic homopolymers of poly(N,N-dimethylacrylamide) (PDMA), poly(ethylene glycol), and poly(4-vinylpyridine) can greatly change both the size/morphology of poly(4-vinylpyridine)-block-polystyrene nanoassemblies and polymerization kinetics. RAFT dispersion polymerization decelerates with the increasing amount of introduced PDMA, and it favors formation of complex block copolymer nanoassemblies in the presence of PDMA. The possible reason for introduced solvophilic homopolymers affecting polymerization kinetics and the block copolymer nanoassemblies is discussed. Adding solvophilic homopolymers into the polymerization medium is believed to be a promising alternative to modulate RAFT dispersion polymerization.

ICAR ATRP in PEG with Low Concentration of Cu(II) Catalyst: A Versatile Method for Synthesis of Block Copolymer Nanoassemblies under Dispersion Polymerization.

A versatile method for synthesis of block copolymer nanoassemblies via initiators for continuous activator regeneration (ICAR) atom transfer radical polymerization (ATRP) dispersion polymerization in a low molecular weight poly(ethylene glycol) (PEG) is discussed. This ICAR ATRP dispersion polymerization uses a low concentration of CuBr2 catalyst, which is stable under atmospheric conditions and is soluble in most polar solvents and employs a polymerization medium of viscous and nonvolatile PEG. Through this ICAR ATRP dispersion polymerization, various block copolymer nanoassemblies, including poly(ethylene glycol)-block-polystyrene, poly(ethylene glycol)-block-poly(methyl methacrylate), and poly(2-hydroxypropyl methacrylate)-block-poly(methyl methacrylate), have been synthesized. The parameters affecting the size and morphology of the block copolymer nanoassemblies are briefly discussed.

Stimulus-Responsive Degradable Polylactide-Based Block Copolymer Nanoassemblies for Controlled/Enhanced Drug Delivery.

Polylactide (PLA) is biocompatible and FDA-approved for clinical use and thus has been a choice of the materials valuable for extensive applications in biomedical fields. However, conventionally designed PLA-based amphiphilic block copolymer (ABP) nanoassemblies exhibit slow and uncontrolled release of encapsulated drugs because of the slow biodegradation of hydrophobic PLA in physiological conditions. To improve potentials for clinical use and commercialization of conventional PLA-based nanoassemblies, stimulus-responsive degradation (SRD) platform has been introduced into the design of PLA-based nanoassemblies for enhanced/controlled release of encapsulated drugs. This review summarizes recent strategies that allow for the development of PLA-based ABPs and their self-assembled nanostructures exhibiting SRD-induced enhanced drug release. The review focuses on the design, synthesis, and evaluation of the nanoassemblies as intracellular drug delivery nanocarriers for cancer therapy. Further, the outlook is briefly discussed on the important aspects for the current and future development of more effective SRD PLA-based nanoassemblies toward tumor-targeting intracellular drug delivery.

In situ synthesis of block copolymer nano-assemblies by polymerization-induced self-assembly under heterogeneous condition

Controlled synthesis of amphiphilic block copolymer nanoparticles in a convenient way is an important and interest topic in polymer science. In this review, three formulations of polymerization-induced self-assembly to in situ synthesize block copolymer nanoparticles are briefly introduced, which perform by reversible addition-fragmentation chain transfer (RAFT) polymerization under heterogeneous conditions, e.g., aqueous emulsion RAFT polymerization, dispersion RAFT polymerization and especially the recently proposed seeded RAFT polymerization. The latest developments in several selected areas on the synthesis of block copolymer nano-assemblies are highlighted.