Copolymer Micelles Research Articles

Lowest gelation concentration in a complex-coacervate-driven self-assembly system, achieved by redox-RAFT synthesis of high molecular weight block polyelectrolytes.

The objective of this work was to synthesize high molecular weight polyelectrolyte complex (PEC) micelles that are effective in controlling the rheology of aqueous solutions at low concentrations, paving the way for industrial applications of thickeners based on the principle of electrostatic self-assembly. Redox-initiated RAFT (reversible addition-fragmentation chain-transfer) polymerization was used to obtain anionic block polyelectrolytes based on poly(sodium 2-acrylamido-2-methylpropane sulfonate) and poly(acrylamide)-poly(AMPS)-block-poly(AM) (di-block) and poly(AMPS)-block-poly(AM)-block-poly(AMPS) (tri-block), with molecular weights of 237 kDa and 289 kDa and polydispersities of 1.29 and 1.34, respectively. A random poly(AMPS)-co-poly(AM) copolymer was also synthesized for comparison. PEC micelles were obtained upon mixing with cationic poly(N-[3-(dimethylamino)propyl]methacrylamide hydrochloride) - poly(DMAPMA), forming viscoelastic gels at unprecedented low concentrations of <3 wt% for the di-block and <1 wt% for the tri-block, which to date is the lowest demonstrated gelation concentration for a synthetic PEC micelle system. Differences between tri-block and di-block architectures are discussed, with the former being more affected by the addition of salt, which is attributed to percolated network breakdown. The random co-polymer was shown not to be an effective thickener but displayed a surprising lack of phase separation upon coacervation. The assemblies were characterized using dynamic light scattering (DLS) and cryo transmission electron microscopy (cryoTEM), revealing spherical micelles with a diameter of approximately 200 nm for the diblock and a mixture of spherical micelles and network particles for the tri-block PEC micelles. The micelles were not affected by dilution down to a polymer concentration of 7.8 × 10-4% (approx. 0.03 μM). Responsiveness to salinity, pH, and temperature was studied using DLS, revealing a critical NaCl concentration of 1.1 M for the block copolymer micelles.

(Invited) Mesoporous Metallic Materials Electrodeposited from Polymeric Micelle Assemblies for Energy Applications

The surfactant-assisted electrodeposition is an effective means to obtain high-quality mesoporous materials in a rather simple synthesis approach. Commercial or home-made block copolymers can be dissolved in aqueous media above their critical micelle concentration to serve as a soft template in the so-called electrodeposition from polymeric micelle assemblies or micelle-assisted electrodeposition in short [1]. The nanoscale porosity of the resulting films, which extends throughout the whole surface and entire film thickness, endow them with large surface-to-volume (S/V) ratios. Such large S/V ratios are particularly amenable for (electro)catalytic applications and, whenever the alloy presents ferromagnetic properties, for magnetoelectric purposes. In our group, mesoporous Cu-Ni, Co-Pt, Ni-Pt and Fe-Pt alloys with pore size around 10 nm have been electrodeposited from Pluronic P-123 containing solutions [2-4]. Similarly, mesoporous Ni films with larger pore diameters (25 - 600 nm) have been deposited using custom-made PS-b-P4VP block copolymer micelles [5]. Even, the double template approach can be utilized to obtain, for example, matrices of mesoporous Co-Pt microdisks when the micelle-assisted electrodeposition is performed on optically lithographed substrates [6], or nanoporous Fe-Pd nanowires using anodized alumina and P-123 as hard and soft templates, respectively [7]. The introduction of an equilibration time between electrolyte preparation and deposition has been determined key in some cases to consistently reproduce the films mesoporosity [8].The electrodeposited mesoporous metallic materials exhibit higher electrocatalytic activity towards hydrogen evolution reaction (HER) in either acid or alkaline media compared to their dense counterparts [3]. In addition, their durability is not severely compromised in spite of the much larger surface exposed to the media. On the other hand, modulation of their magnetic properties with voltage is also possible when these films are electrolyte-gated in aprotic polar solvents like propylene carbonate. The intense electric field strength created at the film / electrolyte interface thanks to the built-in electric double layer allows for tuning of the coercivity (HC) or the saturation magnetization upon voltage application by virtue of different, but often concomitant, mechanisms taking place, like charge carrier accumulation and oxygen migration [6,9]. Variations greater than 30% in HC have been achieved.In this talk I will summarize the main synthesis-wise milestones achieved during the research in the field and the benefits brought by mesoporous alloys to electrocatalysis and magnetoelectricity.[1] C. Li et al. Acc. Chem. Res. 51 (2018) 1764[2] J. Zhang et al. ACS Appl. Mater. Interfaces 10 (2018) 14877[3] K. Eiler et al. Appl. Cat. B 265 (2020) 118597[4] E. Isarain‐Chávez et al. ChemSusChem 11 (2018) 367[5] R. Fagotto Clavijo et al. Cat. Today, in press.[6] C. Navarro-Senent et al. ACS Appl. Mater. Interfaces 10 (2018) 44897[7] D. Raj et al. Nanomaterials 13 (2023) 403[8] C. Navarro-Senent et al. Electrochim. Acta 358 (2020) 136940[9] C. Navarro-Senent et al. APL Materials 7 (2019) 030701

Correction to “Role of Distance from Equilibrium in the Fragmentation Kinetics of Block Copolymer Micelles”

Correction to “Role of Distance from Equilibrium in the Fragmentation Kinetics of Block Copolymer Micelles”

Functionalization of graphene oxide with amphiphilic block copolymer to enhance antibacterial activity

Functionalization of GO with an amphiphilic block copolymer is designed with an aim to enhance its biocompatibility, however, long copolymer chains can screen the blade effect of GO to sacrifice its antimicrobial activities. To solve this problem, low molecular weight of poly(ethylene glycol) (PEG), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and their block copolymer were respectively introduced onto GO via an isophorone diisocyanate modified GO as a intermediate, followed by a solvent evaporation of an oil-in-water emulsion treatment (SE treatment) to induce block copolymer into polymer micelle via phase separation to refresh the sharp edges of GO. Block copolymer modified GO possessed similar dispersibility and stability to PEG modified GO, and even higher loading capacity of the hydrophobic drug than PHBV modified GO, illustrating its superior properties to homopolymer. PEG, PHBV and their block copolymer modified GO were nontoxic towards ATDC5 cells while cultured for 3 days and compatible with erythrocytes within 8 h. SE treatment enhanced greatly the loading capacity of the hydrophobic drug and the accumulative release reached 91.3% within 24 h. The inhibition zone of the block copolymer modified GO was 14.1 mm and 14.8 mm against E. coli and S. aureus, comparable to that of PEG modified GO. The bacterial reduction rate of the copolymer micelle modified GO was 87.1% and 82.7% towards E. coli and S. aureus, much greater than that of PEG, PHBV and their block copolymer modified GO at a concentration of 1 mg/mL. The antibiofilm capacity of the copolymer micelle modified GO were equal to that of PEG modified, demonstrating its great promise in tissue engineering application for repair of infected tissue defects.

Clickable polyethyleneimine incorporated into triblock copolymeric micelles as an efficient platform in the delivery of siRNA to NSCLC cells

The efficacy of transfection vectors to cross the endosomal membrane into the cytosol is a central aspect in the development of nucleic acid-based therapeutics. The challenge remains the same: Delivery, Delivery, Delivery. Despite a rational and appropriate construct of triblock polymeric micelles, which could serve as an ideal platform for the co-delivery of siRNAs and hydrophobic anticancer drugs, we show here its inability to properly convey oligonucleotides to their final destination. In order to overcome biological barriers, a linear PEI comprising two orthogonal groups was synthesized, holding an appropriate balance between safety and efficacy. Micellar carriers were then formulated with this polymer to enhance endosomal siRNA release. This chemical technology also addresses the two major challenges to consider when developing novel micellar products for siRNA delivery, namely cytotoxicity of polycations and endosomal escape. Herein, we demonstrate successful release of siRNA using a polymer tailoring strategy combined with a relevant in vitro approach, considering STAT3 as a promising target in the treatment of non-small cell lung cancer (NSCLC).

Nanoscale Self-Assemblies from Amphiphilic Block Copolymers as Proficient Templates in Drug Delivery

This review article emphasizes the current enlargements in the formation and properties of the various nanostructured aggregates resulting from the self-assembly of a variety of block copolymers (BCPs) in an aqueous solution. The development of the different polymerization techniques which produce polymers with a desired predetermined molecular weight and low polydispersity is investigated with regard to their technological and biomedical applications; in particular, their applications as vehicles for drug delivery systems are considered. The solution behavior of amphiphilic BCPs and double-hydrophilic block copolymers (DHBCs), with one or both blocks being responsive to any stimulus, is discussed. Polyion complex micelles (PICMs)/polymersomes obtained from the electrostatic interaction of a polyelectrolyte-neutral BCP with oppositely charged species are also detailed. Lastly, polymerization-induced self-assembly (PISA), which forms nanoscale micellar aggregates with controlled size/shape/surface functionality, and the crystallization-driven self-assembly of semicrystalline BCPs facilitated when one block of the BCP is crystallizable, are also revealed. The scalability of the copolymeric micelles in the drug delivery systems and pharmaceutical formations that are currently being used in clinical trials, research, or preclinical testing is emphasized as these micelles could be used in the future to create novel nanomedicines. The updated literature and the future perspectives of BCP self-assembly are considered.

Response of ionizable block copolymer assemblies to solvent dielectrics: A molecular dynamics study

Ionizable copolymers assembly in solutions is driven by the formation of ionic clusters. Fast clustering of the ionizable blocks often leads to the formation of far-from equilibrium assemblies that ultimately impact the structure of polymer membranes and affect their many applications. Using large-scale atomistic molecular dynamics simulations, we probe the effects of electrostatics on the formation of ionizable copolymer micelles that dominate their solution structure, with the overarching goal of defining the factors that control the assembly of structured ionizable copolymers. A symmetric pentablock ionizable copolymer, with a randomly sulfonated polystyrene center tethered to polyethylene-r-propylene block, terminated by poly(t-butyl styrene), in solvents of varying dielectric constants from 2 to 20, serves as the model system. We find that independent of the solvents, this polymer forms a core–shell micelle with the ionizable segment segregating to the center of the assembly. The specific block conformation, however, strongly depends on the sulfonation levels and the dielectric constant and the polarity of the solvents.

Synthesis, characterization and in vitro release analysis of pluronic F127 copolymer micelles containing quercetin as a hydrophobic drug

Synthesis, characterization and in vitro release analysis of pluronic F127 copolymer micelles containing quercetin as a hydrophobic drug

Copolymer Micelles: A Focus on Recent Advances for Stimulus-Responsive Delivery of Proteins and Peptides.

Historically used for the delivery of hydrophobic drugs through core encapsulation, amphiphilic copolymer micelles have also more recently appeared as potent nano-systems to deliver protein and peptide therapeutics. In addition to ease and reproducibility of preparation, micelles are chemically versatile as hydrophobic/hydrophilic segments can be tuned to afford protein immobilization through different approaches, including non-covalent interactions (e.g., electrostatic, hydrophobic) and covalent conjugation, while generally maintaining protein biological activity. Similar to many other drugs, protein/peptide delivery is increasingly focused on stimuli-responsive nano-systems able to afford triggered and controlled release in time and space, thereby improving therapeutic efficacy and limiting side effects. This short review discusses advances in the design of such micelles over the past decade, with an emphasis on stimuli-responsive properties for optimized protein/peptide delivery.

Excipient-free lyophilization of block copolymer micelles for potential lung surfactant therapy applications

Polymer lung surfactant (PLS) is a polyethylene glycol (PEG)-brushed block copolymer micelle designed for pulmonary surfactant replacement therapy. Saccharides (e.g., sucrose and (2-hydroxypropyl)-β-cyclodextrin) and water-soluble polymers (e.g., PEG), common excipients for lyophilization, were found to severely impair the surface activity of lyophilized PLS. To investigate the feasibility of excipient-free lyophilization of PLS, we studied the effects of both PLS material parameters and lyophilization operating parameters on the redispersibility and surface availability of reconstituted PLS, all without relying on excipients. We found that the redispersibility was improved by three factors; a faster cooling rate during the freezing stage reduced freezing stress; a higher PEG grafting density enhanced dissipating effects; and the absence of hydrophobic endgroups in the PEG block further prevented micelle aggregation. Consequently, the surface availability of PLS increased, enabling the micelle monolayer at the air/water interface to achieve a surface tension below 10 mN/m, which is a key pharmaceutical function of PLS. Moreover, the lyophilized micelles in powder form could be easily dispersed on water surfaces without the need for reconstitution, which opens up the possibility of inhalation delivery, a more patient-friendly administration method compared to instillation. The successful excipient-free lyophilization unlocks the potential of PLS for addressing acute respiratory distress syndrome (ARDS) and other pulmonary dysfunctions.

Triptolide combined with cyclopamine loaded in polymeric micelles: molecular dynamics, preparation and in vitro antitumor activities

Both triptolide (TP) and cyclopamine (CPA) exhibit strong anticancer effects in vitro with adverse reactions and low bioavailabilities because of their water insolubility and poor liposolubility. The preparation of functional polymer materials into micelles not only improved the apparent solubility of the drug, changed the release behavior of the drug, but also made the drug targeted. All-atom molecular dynamics (MD) methods were used to simulate the states of both TP and CPA in PLA-PEG block copolymer micelles. MD results showed that TP and CPA were concentrated in the core layer of micelles formed by PLA-PEG block copolymers. The polymers PLLA-PEG-COOH were synthesized using HO-PEG-COOH and PLA and characterized by FTIR, 1H NMR, 13 C NMR, and gel chromatography. The dual drug-loaded polymeric micelle ((TP + CPA)-PM) was prepared by solvent evaporation, and the encapsulation rates of TP and CPA were 65.44% and 78.16% using the HPLC method, respectively. The polymer micelles were nearly spherical and did not aggregate under transmission electron microscopy (TEM), and the particle size was about 75.32 ± 0.20 nm through dynamic light scattering (DLS). (TP + CPA)-PM showed similar inhibitory effects to free drugs on A2780, A549, HepG2, and SKOV3 cells, which was proved by the MTT proliferation inhibition experiment, Hoechst33258 fluorescence staining experiment, and flow cytometry experiment. These results appeared to support the assumption that polymeric micelles encapsulation did not affect drug activity. PLA-PEG block copolymer may be a promising drug delivery vehicle for loading TP and CPA in antitumor therapy.

Development of lactoferrin-coated multifunctional copolymer micelles to cross the blood-brain barrier.

The blood-brain barrier (BBB) prevents pathogens and toxins in the bloodstream from reaching the brain, but also inhibits the delivery of agents intended to treat central nervous system disorders, such as Alzheimer's disease (AD). In this study, we prepared and evaluated a novel nano-delivery vehicle system composed of lactoferrin-conjugated (Lf-PIC@Se) micelles. We used a COOH-PEG-PAsp-PV@Se synthesis-based method to prepare the micelles, which involved self-assembly followed by EDC-NHS coupling. Using glutaminyl cyclase inhibitor 8 as a model encapsulated chemical, Lf-PIC@Se micelles achieved a good loading capacity. In vitro analysis demonstrated that Lf-PIC@Se/8 micelles were stable in both neutral and acidic pH solutions in the presence or absence of H2O2, and confirmed their biosafety and compatibility in PC12 and bEND.3 cells. Notably, the cell uptake of Lf-PIC@Se/C6 micelles was much higher than that of PIC@Se micelles, and occurred through LfR-mediated endocytosis. The presence of Se meant that Lf-PIC@Se micelles acted as ROS scavengers in PC12 cells under H2O2-induced oxidative stress, which inhibited oxidative damage and increased mitochondrial membrane potential. Hemolysis assays further demonstrated that Lf-PIC@Se represent a biocompatible carrier. Finally, in vivo experiments in mice suggested that Lf-PIC@Se micelles successfully crossed the BBB, confirming their potential as vehicles for drug delivery when treating AD and other central nervous system disorders.

Copolymeric Micelles of Poly(ε-caprolactone) and Poly(methacrylic acid) as Carriers for the Oral Delivery of Resveratrol.

In this study, we report the development of a micellar system based on a poly(methacrylic acid)-b-poly(ε-caprolactone)-b-poly(methacrylic acid) triblock copolymer (PMAA16-b-PCL35-b-PMAA16) for the oral delivery of resveratrol. The micellar nanocarriers were designed to comprise a PCL core for solubilizing the poorly water-soluble drug and a hydrated PMAA corona with bioadhesive properties for providing better contact with the gastrointestinal mucosa. The micelles were first formed in an aqueous media via the solvent evaporation method and then loaded with resveratrol (72% encapsulation efficiency). Studies by transmission electron microscopy (TEM) and dynamic and electrophoretic light scattering (DLS and PALS) revealed a spherical shape, nanoscopic size (100 nm) and a negative surface charge (-30 mV) of the nanocarriers. Loading of the drug slightly decreased the hydrodynamic diameter (Dh) and increased the ƺ-potential of micelles. In vitro dissolution tests showed that 80% and 100% of resveratrol were released in 24 h in buffers with pH 1.2 and 6.8, respectively, whereas for the same time, not more than 10% of pure resveratrol was dissolved. A heat-induced albumin denaturation assay demonstrated the advantage of the aqueous micellar formulation of resveratrol, which possessed anti-inflammatory potential as high as that of the pure drug. Further, the micellar resveratrol (5 µM) exerted a strong protective effect and maintained viability of mucosa epithelial HT-29 cells in a co-cultural model, representing the production of inflammatory cytokines. For comparison, the pure resveratrol at the same concentration did not protect the damaged HT-29 cells at all. Thus, the present study revealed that the PMAA-b-PCL-b-PMAA copolymeric micelles might be considered appropriate nanocarriers for the oral delivery of resveratrol.

Toward Effective and Adsorption-Based Antifouling Zipper Brushes: Effect of pH, Salt, and Polymer Design.

The undesired spontaneous deposition and accumulation of matter on surfaces, better known as fouling, is a problematic and often inevitable process plaguing a variety of industries. This detrimental process can be reduced or even prevented by coating surfaces with a dense layer of end-grafted polymer: a polymer brush. Producing such polymer brushes via adsorption presents a very attractive technique, as large surfaces can be coated in a quick and simple manner. Recently, we introduced a simple and scalable two-step adsorption strategy to fabricate block copolymer-based antifouling coatings on hydrophobic surfaces. This two-step approach involved the initial adsorption of hydrophobic-charged diblock copolymer micelles acting as a primer, followed by the complexation of oppositely charged-antifouling diblock copolymers to form the antifouling brush coating. Here, we significantly improve this adsorption-based zipper brush via systematic tuning of various parameters, including pH, salt concentration, and polymer design. This study reveals several key outcomes. First of all, increasing the hydrophobic/hydrophilic block ratio of the anchoring polymeric micelles (i.e., decreasing the hydrophilic corona) promotes adsorption to the surface, resulting in the most densely packed, uniform, and hydrophilic primer layers. Second, around a neutral pH and at a low salt concentration (1 mM), complexation of the weak polyelectrolyte (PE) blocks results in brushes with the best antifouling efficacy. Moreover, by tuning the ratio between these PE blocks, the brush density can be increased, which is also directly correlated to the antifouling performance. Finally, switching to different antifouling blocks can increase the internal density or strengthen the bound hydration layer of the brush, leading to an additional enhancement of the antifouling properties (>99% lysozyme, 87% bovine serum albumin).

Hydration State on Poly(ethylene glycol)-Bearing Homopolymers and Random Copolymer Micelles: In Relation to the Thermoresponsive Property and Micellar Structure

Hydration State on Poly(ethylene glycol)-Bearing Homopolymers and Random Copolymer Micelles: In Relation to the Thermoresponsive Property and Micellar Structure

Surface Pressure-Area Mechanics of Water-Spread Poly(ethylene glycol)-Based Block Copolymer Micelle Monolayers at the Air-Water Interface: Effect of Hydrophobic Block Chemistry.

Amphiphilic block copolymer micelles can mimic the ability of natural lung surfactant to reduce the air-water interfacial tension close to zero and prevent the Laplace pressure-induced alveolar collapse. In this work, we investigated the air-water interfacial behaviors of polymer micelles derived from eight different poly(ethylene glycol) (PEG)-based block copolymers having different hydrophobic block chemistries to elucidate the effect of the core block chemistry on the surface mechanics of the block copolymer micelles. Aqueous micelles of about 30 nm in hydrodynamic diameter were prepared from the PEG-based block copolymers via equilibration-nanoprecipitation (ENP) and spread on the water surface using water as the spreading medium. Surface pressure-area isotherm and quantitative Brewster angle microscopy (QBAM) measurements were performed to investigate how the micelle/monolayer structures change during lateral compression of the monolayer; widely varying structural behaviors were observed, including the wrinkling/collapse of micelle monolayers and deformation and/or the desorption of individual micelles. By bivariate correlation regression analysis of surface pressure-area isotherm data, it was found that the rigidity and hydrophobicity of the hydrophobic core domain, which are quantified by glass-transition temperature (Tg) and water contact angle (θ) measurements, respectively, are coupled factors that need to be taken into account concurrently in order to control the surface mechanical properties of polymer micelle monolayers; micelles having rigid and strongly hydrophobic cores exhibited high surface pressure and a high compressibility modulus under high compression. High surface pressure and a high compressibility modulus were also found to be correlated with the formation of wrinkles in the micelle monolayer (visualized by Brewster angle microscopy (BAM)). From this study, we conclude that polymer micelles based on hydrophobic block materials having higher Tg and θ are more suitable for surfactant replacement therapy applications that require the therapeutic surfactant to produce a high surface pressure and modulus at the alveolar air-water interface.

Post‐Polymerization Modifications to Prepare Biomedical Nanocarriers with Varying Internal Structures, their Properties and Impact on Protein Corona Formation

AbstractThe reactive ester approach provides access to various types of drug delivery systems. Either amphiphilic block copolymer micelles with hydrophobic cores can be generated for encapsulation of hydrophobic drugs, or they are (reversibly) crosslinked by polar molecules into nano(hydro)gel particles affording hydrophilic cores and coronas. Beyond short oligonucleotides complexation or covalent drug conjugation inside the core, a surface functionalization with targeting units is further possible to address a large variety of drug delivery scenarios. Interestingly, the reactive ester approach can thereby not only govern the nanocarriers' inner structure and surface property, but at the same time also provide strategies to prevent protein corona formation. These features are summarized in this article and underline the concept of reactive ester macromolecules as beneficial tool for assisting in drug delivery.

Study of the Effect of Nonselective Organic Solvent Nature on the Self-Organization of Amphiphilic Block Copolymers of D,L-Lactide and Ethylene Oxide in Aqueous Solution

The self-organization of biocompatible amphiphilic block copolymers of D,L-lactide and ethylene oxide with various hydrophobic poly(D,L-lactide) block length in aqueous media has been investigated. It has been shown that the nature of nonselective organic solvent has a considerable effect on the size, size polydispersity, and morphology of micelles of a block copolymer with a long poly(D,L-lactide) block. To elucidate the dependence of properties of block copolymer micelles on the common organic solvent type (acetone, tetrahydrofuran, N,N-dimethylformamide, and acetonitrile) various parameters of the used solvents have been estimated, and correlation between the Flory–Huggins coefficient and the surface tension between the hydrophobic block and the nonselective organic solvent and the parameters of micellar structures has been found.

Micellization of Diblock Copolymers in Polymeric Solvents

Micellization of Diblock Copolymers in Polymeric Solvents

Ultrasound-responsive copolymeric micelles prepared by RAFT polymerization using a difunctional spiropyran-based RAFT agent: Investigation of mechanochromism kinetics, responsivities, and enhanced spiropyran mechanoactivation within micelles

An in-depth investigation of the ultrasonic response of mechanophores containing weak covalent bonds within nanosized aggregates is vital for ultrasound imaging, drug delivery, and sensors. In this work, well-defined amphiphilic block SP-[poly(methyl methacrylate-b-N-isopropylacrylamide)]2SP-[p(MMA-b-NIPAM)]2 (P1) and amphiphilic random, SP-[poly(methyl methacrylate-r-N-isopropylacrylamide)]2SP-[p(MMA-r-NIPAM)]2 (P2) copolymers with SP mechanophore embedded at midpoint polymer chain are prepared by RAFT (reversible addition-fragmentation chain transfer) polymerization using a pre-synthesized novel functional bi (trithiocarbonate) and spiropyran (SP)-based RAFT reagent. Both P1 and P2 copolymers self-assemble in spherical micelles in AcCN/water mixed solvents, and several assemblies with different water contents are fabricated. The structural differentiation between block P1 and random P2 dominates the inverse influence of water content on the aggregate sizes of micelles. Under ultrasound irradiation, the SP mechanophore is activated within both micelles, and the amount of activated SP mechanophore increases progressively with prolonged sonication time. For P1, the mechanochemical reaction (mechanochromism) kinetics in an aggregated state and a single chain state are different, while that of P2 micelles and liner are similar, inferred to be associated with the structure difference between both micelles. The mechanoactivation of SP mechanophore within micelles in AcCN/water mixed solvents is higher than in dissolved state due to the micellization of P1 and P2, entangling the hydrophobic PMMA segments and partially swelling in the micellar core. Moreover, an increase in the medium's dielectric constant around the core's SP is also observed, promoting the SP mechanoactivation. This approach may provide a new strategy for preparing novel mechanophore-centered amphiphilic copolymers with colorful structures and high hydrophilicity. These can self-aggregate into nanoparticles in aqueous or mixed solutions, exhibiting effective effects of ultrasonic responsiveness. We expect this work to push forward the in-depth studies on the ultrasonic responsive mechanism of assembly and help open new research avenues into the mechanochemical reactions within nanosized aggregates.