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Amyloid-ß (Aß) species (Aß fibrils and Aß plaques), as one of the typical pathological markers of Alzheimer's disease (AD), plays a crucial role in AD diagnosis. Currently, some near-infrared I (NIR I) Aß probes have been reported in AD diagnosis. However, they still face challenges such as strong background interference and the lack of effective probe design. In this study, we propose molecular design strategy that incorporates CN group and amphiphilic modulation to synthesize a series of amphiphilic NIR I Aß probes, surpassing the commercial probe ThT and ThS. Theoretical calculations indicate that these probes exhibit stronger interaction with amino acid residues in the cavities of Aß. Notably, the probes containing CN group display the ability of binding two distinct sites of Aß, which dramatically enhanced the affinity to Aß species. Furthermore, these probes exhibit minimal fluorescence in aqueous solution and offer ultra-high signal-to-noise ratio (SNR) for in vitro labeling, even in wash-free samples. Finally, the optimal probe DM-V2CN-PYC3 was utilized for in vivo imaging of AD mice, demonstrating its rapid penetration through the blood-brain barrier and labelling to Aß species. Moreover, it enabled long-term monitoring for a duration of 120 min. These results highlight the enhanced affinity and superior performance of the designed NIR I Aß probe for AD diagnosis. The molecular design strategy of CN and amphiphilic modulation presents a promising avenue for the development Aß probes with low background in vivo/in vitro imaging for Aß species.

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Most chemotherapeutic agents are poorly soluble in water, have low selectivity, and cannot reach the tumor in the desired therapeutic concentration. On the other hand, sensitive hydrophilic therapeutics like nucleic acids and proteins suffer from poor bioavailability and cell internalization. To solve this problem, new types of controlled release systems based on nano-sized self-assemblies of cyclodextrins able to control the speed, timing, and location of therapeutic release are being developed. Cyclodextrins are macrocyclic oligosaccharides characterized by a high synthetic plasticity and potential for derivatization. Introduction of new hydrophobic and/or hydrophilic domains and/or formation of nano-assemblies with therapeutic load extends the use of CDs beyond the tried-and-tested CD-drug host-guest inclusion complexes. The recent advances in nano drug delivery have indicated the benefits of the hybrid amphiphilic CD nanosystems over individual CD and polymer components. This review provides a comprehensive overview of the most recent advances in the design of CDs self-assemblies and their use for delivery of a wide range of therapeutic molecules. It aims to offer a valuable insight into the many roles of CDs within this class of drug nanocarriers as well as current challenges and future perspectives.

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In aqueous environment amphiphilic molecules organize themselves into supramolecular structures deeply affecting the chemo-physical properties. Supramolecular assemby is also crucial in the pharmaceutical development of bioactive lipophilic molecules whose attitude to self-aggregate is a recognized factor affecting the in vivo pharmacokinetic, but can also play a crucial role in the interaction with the biological targets in in vitro tests. In aqueous solution, amphiphilic drugs exist in a complex equilibrium involving free monomers, oligomers and larger supramolecular aggregates held together by noncovalent bonds. In this review we focus our attention on the dual effect of drugs self-assembly, which can both reduce the availability of active compounds and create multivalent scaffolds, potentially improving binding affinity and avidity to cellular targets. We examine the effect of aggregation on different classes of amphiphatic molecules with significant biological activities, such as immunomodulatory, anti-tumor, antiviral, and antibiotic. Our purpose is to provide a comprehensive overview of how supramolecular chemistry influences the pharmacological and biological responses of amphiphilic molecules, emphasizing the need to consider these effects in early-stage drug development and in vitro testing. By elucidating these phenomena, this review aims to offer insights into optimizing drug design and formulation to overcome challenges posed by self-aggregation.

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A novel ionophore-based fluorescent nanosensor has been successfully fabricated for the sensitive and selective detection of Cu2+ ions. The nanosensor was constructed through self-assembly of amphiphilic block copolymers, incorporating elesclomol as a Cu2+ ionophore and long-chain dialkylcarbocyanines (DiD) as a fluorescent dye. This design exhibits an "ON/OFF" fluorescence response, where Cu2⁺ ions are selectively sequestered within the nanosensors, resulting in fluorescence quenching of DiD. This strategy enables rapid and highly selective Cu2⁺ sensing with remarkable fluorescence quenching efficiency (up to 93.5 %) and an exceptionally low detection limit of 28.6 nM. The linear detection range extends over two orders of magnitude (0.05-10 µM). Furthermore, the feasibility of this nanosensor for practical applications was confirmed through successful determination of Cu2+ in real water and beer samples, with excellent recovery rates. This nanosensor offers advantages of simplicity, rapidity, and cost-effectiveness, holding significant potential for sensitive and selective Cu2+ detection in various biological and environmental samples.

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Engineering of hollow particles with tunable internal structures often requires complicated processes and/or invasive cleavage. Halogen-bond driven 3D confined-assembly of block copolymers has shed light on the engineering of polymer organization along with the fabricating of unique nanostructures. Herein, a family of multilevel hollow-structured particles (e.g., fully porous, multi-chamber, multi-shell, and concentric multi-layer architectures) is reported via halogen-bond regulated 3D confined-assembly of amphiphilic polymer networks. To do so, polystyrene-b-poly(2-vinyl pyridine)-b-poly(ethylene oxide) (PS-b-P2VP-b-PEO) amphiphilic triblock copolymer is selected, where P2VP blocks act as halogen acceptor. Meanwhile, poly(3-(2,3,5,6-tetrafluoro-4-iodophenoxy) propyl acrylate) (PTFIPA) is employed as halogen donor. Halogen-bond driven donor-acceptor linking between PTFIPA and P2VP block presented in PS-b-P2VP-b-PEO, can lead to the formation of supramolecular polymeric networks, along with the increased P2VP domain and tunable hydrophobic volume. Therefore, an adjustable packing parameter (p) is thus anticipated, which can enable the morphology transformation sequence until an equilibrium state is reached. Moreover, computer simulations are further utilized as the tool to interpret such morphologies transition and identify the precise distribution of each component. Benefiting from the tunable hollow structure and a substantial surface for transporting purpose, these structurally novel particles open perspectives toward promising applications including encapsulation, nanoreactor, and catalyst support.

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Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen causing infections in hospitals and the community, and there is an urgent need for the development of novel antibacterials to combat MRSA infections. Herein, a series of amphiphilic honokiol derivatives containing an oxazolethione moiety were prepared and evaluated for their in vitro antibacterial and hemolytic activities. The screened optimal derivative, I3, exhibited potent in vitro antibacterial activity against S. aureus and clinical MRSA isolates with MIC values of 2-4 µg/mL, which was superior to vancomycin in terms of its rapid bactericidal properties and was less susceptible to the development of resistance. The SARs analysis indicated that amphiphilic honokiol derivatives with fluorine substituents had better antibacterial activity than those with chlorine and bromine substituents. In vitro and in vivo toxicity studies revealed that I3 has relatively low toxicity. In a MRSA-infected mouse skin abscess model, I3 (5 mg/kg) effectively killed MRSA at the infected site and attenuated the inflammation effects, comparable to vancomycin. In a MRSA-infected mouse sepsis model, I3 (12 mg/kg) was found to significantly reduce the bacterial load in infected mice and increase survival of infected mice. Mechanistic studies indicated that I3 has membrane targeting properties and can interact with phosphatidylglycerol (PG) and cardiolipin (CL) of MRSA cell membranes, thereby disrupting MRSA cell membranes, further inducing the increase of reactive oxygen species (ROS), protein and DNA leakage to achieve rapid bactericidal effects. Finally, we hope that I3 is a potential candidate molecule for the development of antibiotics to conquer superbacteria-related infections.

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The foamability of dissolved phosphogypsum from the phosphate fertilizer factories of Gabes (SE Tunisia) is a spectacular phenomenon that has not yet been thoroughly studied. The main objective of this research was to investigate the organic properties of phosphogypsum foam (PGF) to understand its formation process, determine the origin of its enhanced radiochemical contaminants load, and identify its role in pollutants dispersion in marine environment of the Southern Mediterranean Sea. This study identified PGF as an unnatural, surfactant-stabilized, and ephemeral aqueous foam. PGF-forming process comprises three main steps: (i) formation (through phosphogypsum dissolution), (ii) stabilization (facilitated by organic surfactants and gypsum crystals), and (iii) destabilization (geochemical (involving the dissolution of the PGF skeleton gypsum) and/or mechanical (influenced by wind and wave action)). The amphiphilic nature of PGF organic matter and the presence of specific organic groups are responsible for its high toxic contaminants load. PGF contributes, through its elevated pollutants content and its ability to migrate far from its source, to the marine dispersion of industrial toxic radiochemical contaminants. It is therefore recommended to mitigate the environmental and health risks associated with PGF, including banning the discharge of untreated phosphogypsum and other industrial wastes into the coastal environment of Gabes.

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Organophosphate (OP) intoxication has become a severe common health matter all over the world. For the treatment of acute OP poisoning, the effective intracerebral delivery of acetylcholinesterase reactivators is crucial. Here, an amphiphilic hydrazide-pillar[5]arene (HP5A-6C), which could be readily integrated into liposomal bilayers' zwitterionic disaturated phosphatidylcholine (DSPC), was synthesized. A T7 peptide-containing guest (G) was attached on the surface via a noncovalent interaction to make mixed liposomes a particularly appealing candidate for brain-targeting delivery. Such coassembly could remain stable at room temperature for up to 6 weeks, and safety evaluations initially verified its fine biological compatibility. The hydrophilic interiors of T7/HP5A-6C@DSPC could further load HI-6 with 89.70% encapsulation efficiency. Support for brain-targeting potency came from imaging results. Notably, intravenous injection of HI-6-loaded vesicles exhibited a remarkable therapeutic effect on paraoxon (POX)-poisoned mice, effectively alleviating seizures and brain damage and significantly increasing the improving survival rate to 60% over the course of 7 days.

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The development of nontoxic antifouling coatings in static marine environments is urgent. Herein, the successful synthesis of sulfobetaine borneol fluorinated polymers (PEASBF) by a free radical polymerization method is reported. The PEASBF coatings exhibit outstanding antifouling activity, which effectively resists the adhesion of Bovine serum albumin (FITC-BSA adhesion rate: 0.5%), Pseudomonas sp. (Biofilm: 1.3 absorbance) and Navicula sp. (Diatom attachment rate: 33%). More importantly, the PEASBF coatings display outstanding fouling release properties, achieving a release rate of 98% for Navicula sp., and the absorbance of the Pseudomonas sp. biofilm is only 0.2 under 10 Pa shear stress. XPS and MD studies showed that the fluorinated/isobornyl groups induce more sulfobetaine groups to migrate toward polymer surfaces for intensify antifouling. Additionally, the chiral stereochemical structure of borneol enhances antifouling and fouling release ability of amphiphilic polymers. Therefore, the PEASBF has the potential for static marine antifouling applications.

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This study proposed the evolution of self-assembled amphiphilic colloidal particles in Strong-Flavor (SF) Baijiu based on Ostwald ripening for the first time. The evolution process occurs in two stages: disordered amphiphilic molecules self-assemble into small colloidal particles and subsequently undergo Oswald ripening to form larger hydrophobic particles. Microscopic observations revealed the average size of oil-like spherical colloidal particles in Baijiu increased from 1.86 µm to 2.96 µm while the number of particles decreased by 39.50% during the 16-year cellaring process of SF Baijiu, consistent with the particle size trend observed via laser scattering. During fusion process, the charge-to-mass ratio of positively charged colloidal particles decreased, leading ζ-potential decreased from 23.7 mV to 4.66 mV within 16 years of storage. The electrochemical impedance spectroscopy approach tracked the unidirectional variation in the dielectric constant during evolution of SF Baijiu, reflecting the gradual expansion of colloidal particles, which aligns with the evolution trend observed in molecular dynamics simulations. By integrating direct microscopic observations of amphiphilic colloidal particles with electrochemical techniques, the evolution of Baijiu samples is capable to be evaluated in-situ, laying the foundation for intelligent Baijiu aging monitoring technology.

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Cancer is still ranked among the top three causes of death in the 30- to 69-year-old age group in most countries and carries considerable societal and macroeconomic costs that differ depending on the cancer type, geography, and patient gender. Despite advances in several pharmacological approaches, the lack of stability and specificity, dose-related toxicity, and limited bioavailability of chemotherapy (standard therapy) pose major obstacles in cancer treatment, with multidrug resistance being a driving factor in chemotherapy failure. The past three decades have been the stage for intense research activity on the topic of nanomedicine, which has resulted in many nanotherapeutics with reduced toxicity, increased bioavailability, and improved pharmacokinetics and therapeutic efficacy employing smart drug delivery systems (SDDSs). Polymeric micelles (PMs) have become an auspicious DDS for medicinal compounds, being used to encapsulate hydrophobic drugs that also exhibit substantial toxicity. Through preclinical animal testing, PMs improved pharmacokinetic profiles and increased efficacy, resulting in a higher safety profile for therapeutic drugs. This review focuses on PMs that are already in clinical trials, traveling the pathways from preclinical to clinical studies until introduction to the market.

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The aqueous solution of binary mixtures of amphiphilic copolymers is a potential platform for fabricating mixed polymeric micelles for pharmaceutical applications, particularly in developing drug delivery depots for a poorly water-soluble compound. This study fabricated and investigated binary mixtures of poloxamer 403 (P403) and poloxamer 407 (P407) at varying P403:P407 molar ratios to develop a vehicle for the poorly water-soluble compound, using ibuprofen as a model drug. The cooperative formation of mixed micelles was obtained, and the solubility of ibuprofen in the binary mixtures was enhanced compared to the solubility in pure water and an aqueous single P407 solution. The binary mixture with the P403:P407 molar ratio of 0.75:0.25 at a total polymer concentration of 19% w/v exhibited the temperature dependence of micellization and sol-to-gel characteristics of the thermosensitive mixed micellar gels. It possessed suitable micellization and gelation characteristics for in situ gelling systems. The release of ibuprofen from the thermosensitive mixed micellar depots was sustained through a diffusion-controlled mechanism. The findings can aid in formulating binary mixtures of P403 and P407 to achieve the desired properties of mixed micelles and micellar gels.

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Most adsorbents are currently restricted by their single function in pollutant removal from complex wastewater. Herein, we constructed a versatile chitosan-based adsorbent (MC-DA) by grafting amphoteric copolymers with high pH-responsiveness property, aiming at the removal of multiple ionic contaminants. Specifically, the surface charge and hydrophobicity/hydrophilicity of MC-DA can be finely tuned under different pH conditions. As a result, the effective adsorption of cationic methylene blue (MB) and anionic Acid Orange 7 (AO7) with capacities of 627.4 mg/g and 1146.8 mg/g were achieved respectively, superior to most reported materials. Regarding the characterization results, the adsorption mechanisms for MB adsorption were electrostatic and hydrophobic interactions, while the electrostatic attraction was the main driving force for AO7 adsorption. Apart from the versatile adsorption performance, high acid resistance (pH ≥ 2.0), good reusability and rapid separation property under an external magnetic field suggested MC-DA's promising environmental benefits and practical application potential in water remediation.

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Staphylococcus aureus infections and its biofilm removal is an important concern in health care management. Methicillin-resistant S. aureus is responsible for severe morbidity and mortality worldwide. The extensive use of disinfectants against biofilms has led to negative environmental impacts. Developing new and more potent biofilm eradication agents with minimal detrimental effects on human and environmental health is currently on the agenda. The alkyl esters of L-ascorbic acid (ASCn) are antioxidant amphiphiles, which show antimicrobial capacity against methicillin-sensitive and resistant S. aureus strains. ASC12 and ASC14 formulations are able to kill the persister cells of the deepest layers of the biofilm. We tested the hypothesis that the antimicrobial and antibiofilm capacity found for the ASCn emerges from a combined effect of its amphiphilic and their redox capacity. This mechanism appears related to: I) a larger diffusion capacity of the ASC12 micelles than ASC14 and ASC16 microstructures; II) the neutralization of the ASCn acid hydroxyl when the amphiphile reaches the surface of an anionic surface, followed by a rapid insertion; III) the disruption of cell membrane by alteration of membrane tension and structure and IV) ASCn accumulation in the cell membrane or biofilm extracellular matrix surfaces, reducing functional chemical groups and affecting its biological function.

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Nanodiscs are discoidal lipoproteins that have often been used as vehicles to study membrane proteins in their native configuration. Nanodiscs have been primarily made from synthetic lipids. However, nanodiscs also offer a format by which native lipids can be studied in their natural configuration. Here, we present a method to synthesize nanodiscs from bacterial total lipid extracts using the biothreat agent, Yersinia pestis, as a proof-of-concept. The creation of nanoparticles entirely composed of bacterial lipids supports membrane characterization and vaccine antigen discovery without the inherent safety concerns associated with live bacterial cells of this Tier 1 select agent pathogen.

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Polymer nanomicelles have the advantages of small particle size, improved drug solubility, retention effect and enhanced permeability, so they can be used in the treatment of tumour diseases. The aim of this study was to prepare and optimise a nanomicelle which can improve the solubility of insoluble drugs. Firstly, the carboxyl group of cholesterol succinic acid monoester was grafted with the side chain amino group of O-carboxymethyl chitosan-g-cholesterol succinic acid monoester (CCMC), and its structure was characterized by fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Particle size has an important impact on tissue distribution, cell uptake, permeability and inhibition of tumour tissue. In this study, particle size and polydispersity index (PDI) were selected as indexes to optimise the preparation process of CCMC nanomicelles through single factor experiment, Plackett-Burman experiment, the steepest climbing experiment and response surface design experiment. The optimised CCMC nanomicelles showed an average particle size of 173.9 ± 2.3 nm and a PDI of 0.170 ± 0.053. The Cell Counting Kit-8 assay showed no significant effect on cell viability in the range of 0-1000 µg ml-1concentration. Coumarin-6 (C6) was used as a fluorescent probe to investigate the drug-carrying ability of CCMC nanomicelles. C6-CCMC showed 86.35 ± 0.56% encapsulation efficiency with a drug loading of 9.18 ± 0.32%. Both CCMC and C6-CCMC demonstrated excellent stability in different media. Moreover, under the same conditions, the absorption effect of C6 in C6-CCMC nanomicelles was significantly higher than that of free C6 while also exhibiting good sustained-release properties. Therefore, this study demonstrates CCMC nanomicelles as a promising new drug carrier that can significantly improve insoluble drug absorption.

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HYPOTHESIS: An innovative strategy for designing high-performance demulsifiers is proposed. It hypothesizes that integrating mesoscopic molecular simulations with macroscopic physicochemical experiments can enhance the understanding and effectiveness of demulsifiers. Specifically, it is suggested that amphiphilic hyperbranched polyethyleneimine (CHPEI) could act as an efficient demulsifier in oil-water systems, with its performance influenced by its adsorption behaviors at the oil-water interface and its ability to disrupt asphaltene-resin aggregates. EXPERIMENTS: Several coarse-grained models of oil-water systems, with CHPEI, are constructed using dissipative particle dynamics (DPD) simulation. Following the insights gained from the simulations, a series of CHPEI-based demulsifiers are designed and synthesized. Demulsification experiments are conducted on both simulated and crude oil emulsions, with the process monitored using laser scanning confocal microscopy. Additionally, adsorption kinetics and small angle X-ray scattering are employed to reveal the inherent structural characteristics of CHPEI demulsifiers. FINDINGS: CHPEI demonstrates over 96.7 % demulsification efficiency in high acid-alkali-salt systems and maintains its performance even after multiple reuse cycles. The simulations and macroscopic experiments collectively elucidate that the effectiveness of a demulsifier is largely dependent on its molecular weight and the balance of hydrophilic and hydrophobic groups. These factors are crucial in providing sufficient interfacial active functional groups while avoiding adsorption sites for other surfactants. Collaborative efforts between DPD simulation and macroscopic measurements deepen the understanding of how demulsifiers can improve oil-water separation efficiency in emulsion treatment.

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Bullous keratopathy, a condition severely impacting vision and potentially leading to corneal blindness, necessitates corneal transplantation. However, the shortage of donor corneas and complex surgical procedures drive the exploration of tissue-engineered corneal endothelial layers. This study develops a transparent, amphiphilic, and cell-free membrane for corneal endothelial replacement. The membrane, securely attached to the posterior surface of the cornea, is created by mixing hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethylacrylate (EGDMA) in a 10:1 ratio. A 50 µL volume is used to obtain a 60 µm hydrophobic membrane on both sides, with one side treated with a polyvinylpyrrolidone (PVP) solution. The resulting membrane is transparent, foldable, biocompatible, amphiphilic, and easily handled. When exposed to 20% sulfur hexafluoride (SF6), the hydrophilic side of the membrane adheres tightly to the corneal Descemet's membrane, preventing water absorption into the corneal stroma, and thus treating bullous keratopathy. Histological test confirms its effectiveness, showing normal corneal structure and low inflammation when implanted in rabbits for up to 100 d. This study showcases the potential of this membrane as a viable option for corneal endothelial replacement, offering a novel approach to address donor tissue scarcity in corneal transplantation.

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In this work, fusible microspheres loaded with radiopaque agents as an embolic agent for transcatheter arterial embolization (TAE) are developed. A poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) multi-block copolymer basing polyurethane (PCEU) is synthesized and fabricated into blank microspheres (BMs). The microspheres are elastic in compression test. A clinical contrast agent lipiodol is encapsulated in the microspheres to receive fusible radiopaque microspheres (FRMs). The sizes of FRMs are uniform and range from 142.2 to 343.1 µm. The encapsulated lipiodol acts as the plasticizer to reduce the melting temperature point (Tm) of PECU microspheres, thus, leading to the fusion of microspheres to exhibit efficient embolization in vivo. The performance of FRMs is carried out on a rabbit ear embolization model. Serious ischemic necrosis is observed and the radiopacity of FRMs sustains much longer time than that of commercial contrast agent Loversol in vivo. The fusible and radiopaque microsphere is promising to be developed as an exciting embolic agent.

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Aqueous emulsion polymerization is a robust technique for preparing nanoparticles of block copolymers; however, it typically yields spherical nanoassemblies. The scale preparation of nanoassemblies with nonspherical high-order morphologies is a challenge, particularly 2D core-shell nanosheets. In this study, the polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are combined to demonstrate the preparation of 2D nanosheets and their aggregates via aqueous reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. First, the crucial crystallizable component for CDSA, hydroxyethyl methacrylate polycaprolactone (HPCL) macromonomer is synthesized by ring opening polymerization (ROP). Subsequently, the RAFT emulsion polymerization of HPCL is conducted to generate crystallizable nanomicelles by a grafting-through approach. This PISA process simultaneously prepared spherical latices and bottlebrush block copolymers comprising poly(N',N'-dimethylacrylamide)-block-poly(hydroxyethyl methacrylate polycaprolactone) (PDMA-b-PHPCL). The latexes are now served as seeds for inducing the formation of 2D hexagonal nanosheets, bundle-shaped and flower-like aggregation via the CDSA of PHPCL segments and unreacted HPCL during cooling. Electron microscope analysis trace the morphology evolution of these 2D nanoparticles and reveal that an appropriate crystallized component of PHPCL blocks play a pivotal role in forming a hierarchical structure. This work demonstrates significant potential for large-scale production of 2D nanoassemblies through RAFT emulsion polymerization.