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Achieving structural reconfiguration of supramolecular bottlebrush block copolymers toward topological engineering is of particular interest but challenging. Here, we address the creation of supramolecular architectures to discover how assembled topology influences the structured aggregates, combining hydrogen-bonded (H-bonded) bottlebrush block copolymers and electrostatic interaction induced polymer/inorganic eutectics. We first design H-bonding linear-brush block copolymer P(NBDAP-co-NBC)-b-P(NBPEO), bearing linear block P(NBDAP-co-NBC) (poly(norbornene-terminated diaminopyridine-co-norbornene-terminated hexane)) with pendant H-bonding DAP (diaminopyridine) motifs, and PEO (poly(ethylene oxide)) densely grafted P(NBPEO) brush block. Thanks to H-bonding association between DAP and thymine (Thy), incorporation of Thy-functionalized polystyrene (Thy-PS) enables solution self-assembly and formation of H-bonded bottlebrush block copolymers, generating augmented nanospheres with increasing Thy-PS amount. Noteworthy that integration of inorganic cluster silicotungstic acid (STA) to P(NBC-co-NBDAP)-b-P(NBPEO), endows the formation of PEO/STA eutectic core. Therefore, co-crystallization-assistant self-assembly at the interfaces of polymeric, inorganic and supramolecular chemistry is realized, reflecting multi-stage morphology transformation from hexagonal platelets, needle-like, curved rod-like micelles, finally to end-to-end closed rings, by gradually increasing Thy-PS while fixing STA content. Interestingly, such solution self-assembly to co-crystallization-assistant self-assembly strategy not only endows unique nanostructure transition, also induce in-to-out switch of PS domains. These findings clearly provide unique methodology towards programmable fabrication of geometrical objects promising in smart materials.
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In this work, it is reported that large-area (centimeter-scale) arrays of non-close-packed polystyrene-tethered gold nanorod (AuNR@PS) can be prepared through a liquid-liquid interfacial assembly method. Most importantly, the orientation of AuNRs in the arrays can be controlled by changing the intensity and direction of electric field applied in the solvent annealing process. The interparticle distance of AuNR can be tuned by varying the length of polymer ligands. Moreover, the AuNR@PS with short PS ligand are favorited to form orientated arrays with the assistance of electric field, while long PS ligands make the orientation of AuNRs difficult. The orientated AuNR@PS arrays are employed as the nano-floating gate of field-effect transistor memory device. Tunable charge trapping and retention characteristics in the device can be realized by electrical pulse with visible light illumination. The memory device with orientated AuNR@PS array required less illumination time (1 s) at the same onset voltage in programming operation, compared to the control device with disordered AuNR@PS array (illumination time: 3 s). Moreover, the orientated AuNR@PS array-based memory device can maintain the stored data for more than 9000 s, and exhibits stable endurance characteristic without significant degradation in 50 programming/reading/erasing/reading cycles.
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Metallo-supramolecular polymers represent a powerful platform to construct self-assembled morphologies. Copper-thiourea (Cu-TU) coordination interactions, though have been extensively studied in small molecular system, the role of TU motifs in synthetic polymers using metal-ligand coordination to afford supramolecular aggregation and their morphology are often overlooked. Herein, an amphiphilic random copolymer, poly(oligo(ethylene glycol) ethyl acrylate-r-acylthiourea) (P(OEGEA-r-ATU)), bearing pendant TU motifs behaving as the ligand to coordinate Cu, a design characterized by core-coordinated metallo-supramolecular polymer is rationally synthesized. Indeed, rod-like nano-objects are successfully generated via the self-assembly and coordination interaction between P(OEGEA-r-ATU) and Cu. The spatial distribution of TU moieties in polymer chain, along with their Cu chelating capability, featuring the interchain coordination interaction, is tightly related to metallo-supramolecular polymer organization. The specific Cu-TU coordination interactions enable the prompted robustness and stability of soft P(OEGEA-r-ATU), induce the polymer chain configuration, which eventually furnish efficient fabrication of rod-like nano-objects via straightforward nanoprecipitation procedure. These structural motifs of copper-coordinated, rod-like nano-objects from such metallo-supramolecular polymers endow the potential therapeutic properties, such as anti-inflammatory and antitumor effects.
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Cobre , Tiourea , Cobre/química , Ligandos , Polímeros/química , MetalesRESUMEN
Complete cancer cure and healing are still difficult, owing to its complexity and heterogeneity. Integration of supramolecular forces, for example, hydrogen bonds (H-bonds), to anti-cancer nanomedicine affords new scaffolds for biomedical material decoration, featuring the advantages of dynamic property and easier processability. Here, we target the construction of H-bond-mediated supramolecular polymer micelles, loaded with a chemotherapeutic drug along with a photothermal agent for synergistic chemo-/photothermal therapies (CT/PTT). To do so, we design and synthesize an amphiphilic ABA-type triblock copolymer, bearing H-bonding moiety (barbiturate, Ba) within the middle hydrophobic B block. The presence of pendant Ba moieties within the hydrophobic core promotes the loading capability of methotrexate (MTX) and transportation stability, benefitting from the formation of specific Ba/MTX H-bonding interactions. IR780, a photothermal agent, concomitantly encapsulated via hydrophobic interactions, facilitates the development of a synergistic CT/PTT modalities, where MTX can be released on demand owing to the dissociation of Ba/MTX H-bonding interactions induced by elevated temperature. Such H-bonding nanomedicine possesses enhanced drug loading capacity and transport performance and can also trigger stimuli-responsive drug release in the tumor zone. We believe that H-bonded nanomedicines provide a fine toolbox that is conducive to attaining biomedical requirements with remarkable values in theranostics that are highly promising in clinical applications.
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Hipertermia Inducida , Neoplasias , Doxorrubicina/química , Humanos , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Metotrexato/química , Metotrexato/farmacología , Micelas , Nanomedicina , Neoplasias/tratamiento farmacológico , Terapia Fototérmica , Polímeros/química , Nanomedicina TeranósticaRESUMEN
Chemodynamic therapy (CDT) reflects an innovative cancer treatment modality; however, to enhance its relatively low therapeutic efficiency, rational combination with extra therapeutic modes is highly appreciated. Here, core-coordinated amphiphilic, elliptic polymer nanoparticles (Cu/CBL-POEGEA NPs) are constructed via the self-assembly of a glutathione (GSH)-responsive polymer-drug conjugate, bearing side-chain acylthiourea (ATU) motifs which behave as ligands capable of coordinating Cu(II), such a design is featured by combined chemo (CT)/CDT with dual GSH depletion collectively triggered by the Cu(II) reduction reaction and disulfide bond breakage. To do so, an amphiphilic random copolymer poly[oligo(ethylene glycol)ethyl acrylate-co-thiourea] [P(OEGEA-co-ATU)] is synthesized, followed by conjugation of chlorambucil (CBL) to ATU motifs linked via a disulfide bond, thus yielding the targeted P[OEGEA-co-(ATU-g-CBL)]. In such a system, hydrophilic POEGEA serves as the biocompatible section and ATU motifs coordinate Cu(II), resulting in core-coordinated elliptic Cu/CBL-POEGEA NPs. Benefitting from the GSH-induced reduction reaction, Cu(II) is converted into Cu(I) and subsequently react with endogenous H2O2 to create â¢OH, realizing GSH-depletion-promoted CDT. Additionally, the disulfide bond endows GSH-responsive CBL release and provokes further GSH decline, finally realizing combined CDT/CT toward enhancing antitumor outcomes, and in vitro as well as in vivo studies indeed reveal remarkable efficacy. Such a system can provide valuable advantages to create novel nanomedicines toward cascade antitumor therapy.
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Nanopartículas , Neoplasias , Humanos , Cobre/química , Clorambucilo/farmacología , Polímeros/uso terapéutico , Peróxido de Hidrógeno , Nanopartículas/química , Glutatión/química , Disulfuros , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/patologíaRESUMEN
Among the various challenges in medicine, diagnosis, complete cure, and healing of cancers remain difficult given the heterogeneity and complexity of such a disease. Differing from conventional platforms with often unsatisfactory theranostic capabilities, the contribution of supramolecular interactions, such as hydrogen-bonds (H-bonds), to cancer nanotheranostics opens new perspectives for the design of biomedical materials, exhibiting remarkable properties and easier processability. Thanks to their dynamic characteristics, a feature generally observed for noncovalent interactions, H-bonding (macro)molecules can be used as supramolecular motifs for yielding drug- and diagnostic carriers that possess attractive features, arising from the combination of assembled nanoplatforms and the responsiveness of H-bonds. Thus, H-bonded nanomedicine provides a rich toolbox that is useful to fulfill biomedical needs with unique advantages in early-stage diagnosis and therapy, demonstrating the promising potential in clinical translations and applications. Here the design and synthetic routes toward H-bonded nanomedicines, focus on the growing understanding of the structure-function relationship for efficient cancer treatment are summarized. A guidance for designing new H-bonded intelligent theranostic agents is proposed, to inspire more successful explorations of cancer nanotheranostics and finally to promote potential clinical translations.
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Nanomedicina , Neoplasias , Humanos , Hidrógeno , Enlace de Hidrógeno , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Medicina de Precisión , Nanomedicina TeranósticaRESUMEN
Generally, nanostructured polymer particles are prepared by 3D confined self-assembly (3D-CSA) of block copolymers (BCPs), while micelles are obtained through self-assembly of BCPs in dilute solutions. Herein, a facile yet robust strategy is developed to regulate the assembled structures of BCP, poly(styrene-block-4-vinylpyridine) (PS-b-P4VP), from nanostructured particles to micelles. The assemblies are prepared by an emulsion-solvent diffusion-induced self-assembly route, which is conducted by dialysis. A key feature of this strategy is that a P4VP-selective solvent (e.g., ethanol) is added to the dialysate to tune the interfacial behavior of the droplets and assembled structures of PS-b-P4VP. The authors' results reveal that in the presence of slight ethanol, the surface and internal structural transitions of nanostructured particles are caused by changes in the interfacial selectivity and packing parameter. Interestingly, interfacial instability, which results in the formation of micelles, is observed when the dialysate contains 50 vol% ethanol or more. The reason can be ascribed to the decreased interface tension, which is induced by the increase in ethanol and enhanced solubility of P4VP. This facile strategy provides a new opportunity to bridge the gap between traditional 3D-CSA and solution self-assembly of BCPs, offering a promising route to engineer morphologies and nanostructures of polymeric assemblies.
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Micelas , Polímeros , Soluciones para Diálisis , Emulsiones , Etanol , Polímeros/química , Solventes/químicaRESUMEN
High-performance adhesives are of great interest in view of industrial demand. We herein identify a straightforward synthetic strategy towards universal hydrogen-bonded (H-bonded) polymeric adhesives, using a side-chain barbiturate (Ba) and Hamilton wedge (HW) functionalized copolymer. Starting from a rubbery copolymer containing thiolactone derivatives, Ba and HW moieties are tethered as pendant groups via an efficient one-pot two-step amine-thiol-bromo conjugation. Hetero-complementary Ba/HW interactions thus yield H-bonded supramolecular polymeric networks. In addition to an enhanced polymeric network integrity induced by specific Ba/HW association, the presence of individual Ba or HW moieties enables strong binding to a range of substrates, outstanding compared to commercial glues and reported adhesives.
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Adhesivos , Polímeros , Fenómenos Químicos , Hidrógeno , Enlace de Hidrógeno , Polímeros/químicaRESUMEN
Halogen-bond driven assembly, a world parallel to hydrogen-bond, has emerged as an attractive tool for constructing (macro)molecular arrangement. However, knowledge about halogen-bond mediated confined-assembly in emulsion droplets is limited so far. An I . N bond mediated confined-assembly pathway to enable order-order phase transitions is reported here. Compared to hydrogen bonds, the distinct features of halogen bonds (e.g., higher directionality, hydrophobicity, favored in polar solvents), offers opportunities to achieve novel nanostructures and materials. Polystyrene-b-poly(4-vinyl pyridine) (PS-b-P4VP) AB diblock copolymer is chosen as halogen acceptor, while an iodotetrafluorophenoxy substituted C-type homopolymer, (poly(3-(2,3,5,6-tetrafluoro-4-iodophenoxy)propyl acrylate), PTFIPA) is designed as halogen donor, synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Formation of halogen bonding donor-acceptor pairs between the PTFIPA homopolymer and the P4VP segments presented in PS-b-P4VP, increase the volume of P4VP domains, in turn inducing an order-to-order morphology transition sequence: changing from spherical â cylindrical â lamellar â inverse cylindrical, by tuning the PTFIPA content and choice of surfactant. Subsequent selective swelling/deswelling of the P4VP domains give rise to further internal morphology transitions, creating tailored mesoporous microparticles, disassembled nanodiscs, and superaggregates. It is believed that these results will stimulate further examinations of halogen bonding interactions in emulsion droplets and many areas of application.
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Photonic crystals (PCs) are ideal candidates for reflective color pigments with high color purity and brightness due to tunable optical stop band. Herein, the generation of PC microspheres through 3D confined supramolecular assembly of block copolymers (polystyrene-block-poly(2-vinylpyridine), PS-b-P2VP) and small molecules (3-n-pentadecylphenol, PDP) in emulsion droplets is demonstrated. The intrinsic structural colors of the PC microspheres are effectively regulated by tuning hydrogen-bonding interaction between P2VP blocks and PDP, where reflected color can be readily tuned across the whole visible spectrum range. Also, the effects of both PDP and homopolymer (hPS) on periodic structure and optical properties of the microspheres are investigated. Moreover, the spectral results of finite element method (FEM) simulation agree well with the variation of structural colors by tuning the periodicity in PC microspheres. The supramolecular microspheres with tunable intrinsic structural color can be potentially useful in the various practical applications including display, anti-counterfeit printing and painting.
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Hydrogen bonds (H-bonds) constitute highly relevant structural units of molecular self-assembly. They bridge biological and synthetic sciences, implementing dynamic properties into materials and molecules, not achieved via purely covalent bonds. Phase segregation on the other hand represents another important assembly principle, responsible for, e.g., cell compartimentation, membrane-formation, and microphase segregation in polymers. Yet, despite the expanding elegant synthetic strategies of supramolecular polymers, the investigation of phase behavior of macromolecules driven by H-bonding forces still remains in its infancy. Compared to phase segregation arising from covalently linked block copolymers, the generation of phase segregated nanostructures via supramolecular polymers facilitates the design of novel functional materials, such as those with stimuli-responsive, self-healing, and erasable-material properties. We here discuss the phase segregation of H-bonding polymers in both the solution and solid state, wherein the molecular recognition elements are based on multiple H-bonding moieties, such as thymine/2,6-diamino-pyridine (THY/DAP), thymine/diamino triazine (THY/DAT), and barbiturate/Hamilton wedge (Ba/HW) elements. The specific aggregation of a series of different H-bonding polymers in solution, both linear and dendritic polymers, bearing heterocomplementary H-bonding moieties are described, in particular focusing on the issue of phase segregation. The exploitation of H-bonded supramolecular dendrons with segregating polymer chains leads to the formation of three-phase segregated hierarchical micelles in solution, purely linking the components via H-bonds, in turn displaying a versatile spectrum of segregated morphologies. We also focus on segregation effects of H-bonded amorphous and crystalline polymers: thus the formation of nanostructures, such as disordered micelles and well-ordered body centered cubic (BCC) packed spheres from telechelic polymers bearing H-bonding moieties at the chain ends is observed. Finally, we discuss the discovery of novel functional microphase separated self-healing supramolecular architectures, illustrating dynamic and self-healing properties with an almost complete recovery of the initial mechanical performances healing within 24h at 30 °C. Collectively, our studies prove that phase segregation in H-bonding polymers is an important principle, capable to generate nanostructures and dynamic properties not achieved in covalently linked polymers. The results discussed illustrate that a rational architectural design within H-bonding polymer systems in interplay with phase segregation in both the amorphous and crystalline state opens perspectives to develop artificial supramolecular systems approaching the level of complexities and properties present in nature's biomaterials.
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We report a simple strategy to form three-phase segregated hierarchical micelles via a counterbalanced phase segregation/self-assembly process. Our methodology relies on a cooperative polyphilic phase segregation, paralleled by a self-assembly process induced by hydrogen-bonds to afford the generation of supramolecular multicompartment dendrons. The versatile preparation of such hierarchical morphologies is evidenced on the basis of a series of supramolecular dendrons, composed of semifluorinated copolymers, homopolymers, or nonfluorinated polymers. We do have designed and prepared mid- and α,ω-barbiturate (Ba) functionalized poly(n-butyl acrylates), Ba-(PnBuA-Ba)2, together with a series of heterocomplementary α,ω-Hamilton wedge (HW) functionalized polymers via reversible addition-fragmentation chain transfer (co)polymerization. To enable subtle phase segregation processes, the semifluorinated homo- and copolymers HW-P(nBuA-co-PFPA)-HW (prepared via copolymerization of nBuA with 2,2,3,3,3-pentafluoropropyl acrylate (PFPA)) and HW-PPFPA-HW, as well as the nonfluorinated polymer HW-PnBuA-HW and HW-PI-HW (PI, polyisoprene), have been generated. Selective intermolecular complexation between Ba-(PnBuA-Ba)2 and the complementary polymers (such as HW-P(nBuA-co-PFPA)-HW, HW-PPFPA-HW or HW-PI-HW) leads to the successful generation of supramolecular dendrons as evidenced by (1)H NMR and diffusion-ordered NMR spectroscopy, together with the formation of well-defined disc-like nano-objects as demonstrated by microscopy investigations. Transmission electron microscopy demonstrates a unique, uncommon phase behavior showing remarkable three-phase segregated hierarchical micelles, indicative of the desired micellar multicompartments.
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Enlace de Hidrógeno , Nanoestructuras/química , Polímeros/química , Acrilatos/química , Hidrógeno/química , Espectroscopía de Resonancia Magnética , Micelas , Estructura Molecular , PolimerizacionRESUMEN
Phase segregation between different macromolecules and specific weak interactions are the basis of molecular organization in many biological systems, which are held together by attractive hydrogen bonds (H-bonds) and dissociated by phase segregation. We report significant changes in the association behavior of covalent H-bonds by the phase of attached polymer chains. Depending on the aggregation state, we observed either intact H-bonds despite segregation of the phases, or macrophase separation with a larger amount of H-bonding dissociation.
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Integrating self-healing capability into supramolecular architectures is an interesting strategy, and can considerably enhance the performance and broaden the scope of applications for this important class of polymers. Herein we report the rational design of novel V-shaped barbiturate (Ba) functionalized soft-hard-soft triblock copolymers with a reversible supramolecular healing motif (Ba) in the central part of the hard block, which undergoes autonomic repair at 30 °C. The designed synthesis also offers a suitable macromolecular building block to further self-assemble with heterocomplementary α,ω-Hamilton wedge (HW) functionalized polyisoprene (PI; HW-PI-HW), resulting in an H-shaped supramolecular architecture with efficient self-healing capabilities that can recover up to around 95 % of the original mechanical performance at 30 °C within 24â h.
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The outcomes of combined cancer therapy are largely related to loading content and contribution of each therapeutic agent; however, fine-tuning the ratio of two coloaded components toward precise cancer therapy is a great challenge and still remains in its infancy. We herein develop a supramolecular polymer scaffold to optimize the coloading ratio of chemotherapeutic agent and photosensitizer through hydrogen-bonding (H-bonding) interaction, for maximizing the efficacy of intelligent cancer chemo/photodynamic therapies (CT/PDT). To do so, we first synthesize a thymine (THY)-functionalized tetraphenylporphyrin photosensitizer (i.e., TTPP), featuring the same molecular configuration of H-bonding array with chemotherapeutic carmofur (e.g., 1-hexylcarbamoyl-5-fluorouracil, HCFU). Meanwhile, a six-arm star-shaped amphiphilic polymer vehicle P(DAPA-co-DPMA-co-OEGMA)6 (poly(diaminopyridine acrylamide-co-2-(diisopropylamino)ethyl methacrylate-co-oligo(ethylene glycol) monomethyl ether methacrylate)6) is prepared, bearing hydrophilic and biocompatible POEGMA segment, along with hydrophobic PDAPA and PDPMA segments, characterizing the randomly dispersed dual functionalities, i.e., heterocomplementary H-bonding DAP motifs and pH-responsive protonation DPMA content. Thanks to the identical DAP/HCFU and DAP/TTPP H-bonding association capability, the incorporation of both HCFU and TTPP to six-arm star-shaped P(DAPA-co-DPMA-co-OEGMA)6 vehicle, with an optimized coloading ratio, can be straightforwardly realized by adjusting the feeding concentrations, thus yielding the hydrogen-bonded supramolecular nanoparticles (i.e., HCFU-TTPP-SPNs), demonstrating the codelivery of two components with the promise to optimize the combined CT/PDT efficacy.
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Glicoles de Etileno , Neoplasias , Polímeros , Humanos , Polímeros/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Nanomedicina , Micelas , Neoplasias/tratamiento farmacológico , Metacrilatos/químicaRESUMEN
Injectable hydrogel has attracted appealing attention for skin wound treatment. Although multifunctional injectable hydrogels can be prepared by introducing bioactive ingredients with antibacterial and anti-inflammatory capabilities, their preparation remains complicated. Herein, a polyphenol-based supramolecular injectable hydrogel (PBSIH) based on polyphenol gallic acid and biological macromolecule sodium alginate is developed as a wound dressing to accelerate wound healing. We show that such PBSIH can be rapidly formed within 15 s by mixing the sodium alginate and gallic acid solutions based on the hydrogen bonding and hydrophobic interactions. The PBSIH shows excellent cytocompatibility, antibacterial, and antioxidant properties, which enhance infected wound healing by inhibiting bacterial infection and alleviating inflammation after treatment of 11 days. Moreover, we show that the preparative strategies of injectable supramolecular hydrogels can be extended to other polyphenols, including protocatechuic and tannic acids. This study provides a facile yet highly effective method to design injectable polyphenol- sodium alginate hydrogel for wound dressing based on naturally bioactive ingredients.
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Hidrogeles , Cicatrización de Heridas , Antiinflamatorios/farmacología , Antibacterianos/farmacología , Alginatos , Ácido Gálico/farmacología , Vehículos Farmacéuticos , Polifenoles/farmacologíaRESUMEN
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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One of the major goals of biomedical science is to pioneer advanced strategies toward precise and smart medicine. Hydrogen-bonding (H-bonding) assembly incorporated with an aggregation-induced emission (AIE) capability can serve as a powerful tool for developing supramolecular nanomedicine with clear tumor imaging and smart therapeutic performance. We here report a H-bonded polymeric nanoformulation with an AIE characteristic toward smart antitumor therapy. To do so, we first design a structurally novel tetraphenylethylene (TPE)-based H-bonding theranostic prodrug, TPE-(FUA)4, characterized by four chemotherapeutic fluorouracil-1-acetic acid (FUA) moieties arched to the TPE core. A six-arm star-shaped amphiphilic polymer vehicle, P(DAP-co-OEGEA)6, is prepared, bearing hydrophilic and biocompatible POEGEA (poly(oligo (ethylene glycol) ethyl acrylate) segments, along with a hydrophobic and H-bonding PDAP (poly(diaminopyridine acrylamide)) segment. Thanks to the establishment of the DAP/FUA H-bonding association, incorporating the TPE-(FUA)4 prodrug to the P(DAP-co-OEGEA)6 vehicle can yield H-bond cross-linked nanoparticles with interpenetrating networks. For the first time, AIE luminogens are interwoven into a six-arm star-shaped polymer via an intrinsic H-bonding array of the chemotherapeutic agent FUA, thus imposing an effective restriction of TPE molecular rotations. Concomitantly, encapsulated photothermal agent (IR780) via a hydrophobic interaction facilitates the formation of nanoassemblies, TPE-(FUA)4/IR780@P(DAP-co-OEGEA)6, featuring synergistic cancer chemo/photothermal therapy (CT/PTT). Our study can contribute a practical solution to fulfill biomedical requirements with a conductive advance in precision nanomedicine.
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Tumor recurrence and metastasis are the main causes of cancer mortality; traditional chemotherapeutic drugs have severe toxicity and side effects in cancer treatment. To overcome these issues, here, we present a pH-responsive, self-destructive intelligent nanoplatform for magnetic resonance/fluorescence dual-mode image-guided mitochondrial membrane potential damage (MMPD)/photodynamic (PDT)/photothermal (PTT)/immunotherapy for breast cancer treatment with external near infrared (NIR) light irradiation. To do so, we construct multifunctional monolayer-layered double hydroxide (LDH) nanosheets (MICaP), co-loading indocyanine green (ICG) with ultrahigh loading content realized via electrostatic interactions, and calcium phosphate (Ca3(PO4)2) coating via biomineralization. Such a combined therapy design is featured by the outstanding biocompatibility and provokes immunogenic cell death (ICD) of tumors toward cancer immunotherapy. The active transport of excess Ca2+ released from pH-sensitive Ca3(PO4)2 can induce MMPD of tumor cells to minimize oxygen consumption in the tumor microenvironment (TME). The presence of ICG not only generates singlet oxygen (1O2) to induce apoptosis by photodynamic therapy (PDT) but also initiates tumor cell necrosis by photothermal therapy (PTT) under near-infrared (NIR) light radiation. Eventually, the immune response generated by MMPD/PDT/PTT greatly promotes a cytotoxic T lymphocyte (CTL) response that can limit tumor growth and metastasis. Both in vitro and in vivo studies indeed illustrate outstanding antitumor efficiency and outcomes. We anticipate that such precisely designed nanoformulations can contribute in a useful and advantageous way that is conducive to explore novel nanomedicines with notable values in antitumor therapy.