Self-Assembly of ABC Triblock Copolymer into Giant Segmented Wormlike Micelles in Dilute Solution

We report the self-assembly of a linear ABC triblock copolymer into the previously unknown architecture of giant segmented wormlike micelles (SWMs). The lengths and diameters of these giant SWMs were as high as ca. 10 μm and 500 nm, respectively. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) analysis revealed that the SWMs comprised sequences of repeated elemental parts, i.e., disks having a thickness of ca. 65 nm. A most interesting feature is that disks having different diameters became connected through threads to form various giant segmented wormlike micelles. A kinetic study indicated that the process of SWM formation occurred basically through three stages:  (1) the ABC triblock copolymer self-assembled into small spheres of ca. 38 nm diameter; (2) these small spheres joined together to form intermediate shuttlelike structures; (3) the spheres within the shuttlelike structures rearranged and underwent further adjustment to form the final SWMs

Wormlike Micelles with Microphase-Separated Cores from Blends of Amphiphilic AB and Hydrophobic BC Diblock Copolymers

Wormlike Micelles with Microphase-Separated Cores from Blends of Amphiphilic AB and Hydrophobic BC Diblock Copolymer

Wormlike Micelles with Microphase-Separated Cores from Blends of Amphiphilic AB and Hydrophobic BC Diblock Copolymers

Wormlike Micelles with Microphase-Separated Cores from Blends of Amphiphilic AB and Hydrophobic BC Diblock Copolymer

Wormlike Micelles with Microphase-Separated Cores from Blends of Amphiphilic AB and Hydrophobic BC Diblock Copolymers

Wormlike Micelles with Microphase-Separated Cores from Blends of Amphiphilic AB and Hydrophobic BC Diblock Copolymer

Hydrogen-Bond-Driven Core-Crosslinked Supramolecular Micelles with pH/Thermal/Glutathione-Responsive Drug Release toward Enhanced Cancer Therapy

The field of anticancer nanomedicine seeks to boost the arsenal’s exploitation with intelligent performance. One opportunistic choice comes from the fabrication of amphiphilic polymer micelles that are reversibly crosslinked. Here, hydrogen-bond (H-bond)-driven core-crosslinked supramolecular polymer micelles (FUS/ICG@PEDD) are constructed, co-loading α,ω-functionalized symmetrical H-bonding prodrug 5-fluorouracil-acetic acid–SS–5-fluorouracil-acetic acid (FUS) and a dual photothermal/photodynamic agent (indocyanine green, ICG). Such core-crosslinked nanomedicine is characterized by enhanced drug loading content, crosslinking-prompted stability, pH-responsive charge reversal, and smart drug release, which can facilitate the engineering of synergistic chemo/photothermal/photodynamic therapies (CT/PTT/PDT). To do so, an amphiphilic diblock copolymer, PEG-b-P(DAPA-co-DEAEMA) (denoted as PEDD), is developed to serve as a drug delivery vehicle, with hydrophilic PEG [poly(ethylene glycol)] and hydrophobic P(DAPA-co-DEAEMA) [poly(diaminopyridine acrylamide-co-2-(diethylamino)ethyl methacrylate], bearing randomly dispersed dual functionalities: pH-responsive charge-reversal DEAEMA and H-bonding DAP motifs. Thanks to the specific DAP/FUS H-bonding interactions and two-terminal FU structure of the prodrug, core-crosslinked nanomedicine FUS/ICG@PEDD is thus enabled. In vitro and in vivo investigations indeed reveal remarkable antitumor efficacy. We believe that such H-bonded nanomedicines can fuel the development of intelligent nanomedicines with value in cancer therapy

Ring-Shaped Morphology of “Crew-Cut” Aggregates from ABA Amphiphilic Triblock Copolymer in a Dilute Solution

Ring-Shaped Morphology of “Crew-Cut” Aggregates from ABA Amphiphilic Triblock Copolymer in a Dilute Solutio

Deliver on a Promise: Hydrogen-Bonded Polymer Nanomedicine with a Precise Ratio of Chemodrug and Photosensitizer for Intelligent Cancer Therapy

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

Hydrogen Bond-Mediated Supramolecular Polymeric Nanomedicine with pH/Light-Responsive Methotrexate Release and Synergistic Chemo-/Photothermal Therapy

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

Self-Assembly of ABA Amphiphilic Triblock Copolymers into Vesicles in Dilute Solution

Self-assembly of an ABA amphiphilic triblock copolymer into vesicles in dilute solution was studied by successfully combining experimental methods and a real-space self-consistent field theory in three-dimensional space. It was found experimentally that vesicle size was sensitive to the initial copolymer concentration in the organic solvent. Also, the aggregate morphologies and vesicles sizes were found to be dependent on the annealing time. A number of complex vesicles, such as global, long-style, trigonal, and necklacelike vesicles, were obtained in our experiments. Moreover, the corresponding microstructures were produced in our simulations. The results show that various vesicles in dilute solution are formed solely on account of the inhomogeneous density distribution in the local region in nature. Our simulations confirm that the structural complexity coexisting behavior in the single-amphiphile systems is largely attributed to the metastability rather than the polydispersity of the triblock copolymer. These metastable states should strongly depend on the pathway of the system on the free energy landscapes, which is governed by the initial condition

Well-Ordered Inorganic Nanoparticle Arrays Directed by Block Copolymer Nanosheets

Precise control over the spatial arrangement of inorganic nanoparticles on a large scale is desirable for the design of functional nanomaterials, sensing, and optical/electronic devices. Although great progress has been recently made in controlling the organization of nanoparticles, there still remains a grand challenge to arrange nanoparticles into highly-ordered arrays over multiple length scales. Here, we report the directed arrangement of inorganic nanoparticles into arrayed structures with long-range order, up to tens of microns, by using hexagonally-packed cylindrical patterns of block copolymer nanosheets self-assembled within collapsed emulsion droplets as scaffolds. This technique can be used to generate nanoparticle arrays with various nanoparticle arrangements, including hexagonal honeycomb structures, periodic nanoring structures, and their combinations. This finding provides an effective route to fabricate diverse nanoparticle arrayed structures for the design of functional materials and devices