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process due to the aggressivity (e.g., electroporation or sonication methods), low yield, or poor controllability of traditional methods. [2,3] In addition, because the separation process from donor cells involves cumbersome processing steps, the weakened or lost function of exosomes in this process is difficult to be enhanced or compensated in the process of engineering. [4] In this work, the concept of "independent module/cascading function" is proposed for the controllable construction of engineered exosomes, that is, nanosized artificial module with specific functions is synthesized independently, and then selectively and controllably combined with natural exosome module in a "one-by-one" way to construct engineered exosome. The concept of "independent module" is not limited by the activity conditions of exosomes, so as to greatly enrich the preparation methods and types of artificial modules. Meantime, based on the selective and controllable combination technology between different modules, this method can effectively protect the integrity of exosome membrane structure and the activity of functional proteins and nucleic acids on membrane surface. "Cascading function" refers to endowing exosomes with new functions through rich design of artificial modules, and meeting the complex requirements of disease treatment through cascading effect, so as to play a remarkable therapeutic effect.In addition, this kind of engineered exosomes is applied to the treatment of Parkinson's disease (PD), aiming to solve the challenges of precise targeting and complex needs of PD treatment, of which the pathogenesis is complex and involves many factors and there is no effective method to completely cure it. [5] Up to now, the pathogenesis of PD can be summarized as the following process: nuclear gene mutation of dopaminergic neurons inhibits the normal hydrolysis of α-synuclein (α-syn) and promotes its aggregation in mitochondria, producing high concentration of reactive oxygen species (ROS), which further leads to enhanced expression of inducible nitric oxide synthase (iNOS) and neuroinflammation, and destroys itself and its surrounding neuronal cells. [6] Exosomes derived from stem cells have the potential to promote tissue repair and nerve regeneration, and have the ability to penetrate the blood-brain barrier Current exosome engineering methods usually lead to the damage of exosome morphology and membrane, which cannot meet the complex needs of disease treatment. Herein, the concept of an "independent module/cascading function" is proposed to construct an engineered exosome nanotherapy platform including an independent artificial module and a natural module. The artificial module with movement/chemotaxis function is first synthesized, and then it is controllably combined with the natural exosome module with "one by one" mode through a "differentiated" modification method. The whole process can not only maintain the activity of the natural exosome module, but also endows it with motion ability, so as to realize the purpose of...

We investigated the co-assembly of nanoparticles P and amphiphilic diblock copolymers AB in selective solvents using a dissipative particle dynamics (DPD) method. By controlling the nanoparticle concentration and the interaction parameter between the hydrophobic blocks and the solvents, we found that the aggregation morphology can be changed from rod-like micelles to disk-like micelles and further to vesicles. The ratio of the hydrophobic/hydrophilic block and the nanoparticle concentration largely affects the structural characteristics of vesicles and the dispersion of nanoparticles. Copolymers with a longer hydrophobic block length are more likely to form vesicles with a smaller aqueous cavity size and vesicle size as well as a thicker wall. At the same time, the nanoparticles in the hydrophobic membrane tend to locate closer to the center of the vesicle and they become more compactly organized. A significant discovery has found that the larger the nanoparticle concentration, the smaller the aqueous cavity and the larger the vesicle size. We can also locate the nanoparticles at the center of spherical micelles or the hydrophobic membranes of vesicles by varying the nanoparticle concentration. This provides an effective and simple method to prepare size-controlled vesicles containing nanoparticles, project the localization of nanoparticles within the vesicles, and even tune the distance between the nanoparticles.

Cyclic brush (cb) copolymers that are composed of a cyclic core densely grafted with radiating polymer brushes have emerged recently as innovative materials for both fundamental and practical investigations due to the unique polymer topology-generated properties. The self-assembled microstructures of amphiphilic cb block copolymers in solutions are investigated by dissipative particle dynamic simulation. A series of structures, such as rods, plates, vesicles, large compound vesicles, bilayers, and spheres, are obtained from the solutions at various solvophilic/solvophobic side chain lengths, solvophilic/ solvophobic backbone lengths, and grafting densities. The structures of the representative aggregates are studied. When it comes to vesicles, we find the cavity size decreases and the membrane thickness increases as the solvophobic side chain length or solvophobic backbone length increases with fixed solvophilic side chain length and solvophilic backbone length, and their vesicle sizes are almost the same. The thickness of the plate becomes larger while its width becomes narrower as solvophobic side chain length or solvophobic backbone length increases with fixed solvophilic side chain length and solvophilic backbone length. As regards spheres, the cb amphiphiles can be approximated as cones with the cone height equivalent to the micelle core radius and the cone base area approximated as the cross-sectional area of the solvophilic brush. This model explains well all kinds of parameters (e.g., number of spheres, average number of chains per sphere, radius of gyration of the sphere and its micellar core, and thickness of the micellar shell) measured in simulations. In general, amphiphilic cb copolymers with higher backbone asymmetry and graft asymmetry (i.e., relatively larger solvophilic components) or larger grafting density are expected to form morphologies with progressively more curved interfaces, leading to a morphological transition from vesicles to plates and finally to spheres. We suppose this work could inspire researchers to design structurally complex functional material with broad applications, such as sensing, bioimaging, drug delivery, nano-or microreactors, and optoelectronics.

Both experimental and theoretical studies have shown that a cylinder-forming block copolymer melt under the confinement of a nanopore can self-assemble into an interesting sequence of ordered nanostructures in terms of the pore size, including single cylinder, stacked disks, single helix, double-helix, and so on. However, most of these studies focused on the normal cylinder phase formed by a simple AB diblock copolymer at a low volume fraction (e.g., f A of A-block). Whether this phase sequence is universal or specifically depends on the copolymer architecture is a question to be answered. In particular, when an “inverted” A-cylinder phase is formed by a special type of AB block copolymer at a high volume fraction of f A > 0.5, for example, the A­(AB) n miktoarm star copolymer, whether the phase sequence still exists is an interesting question. In this work, we investigate the self-assembly of cylinder-forming A­(AB) n copolymer confined in nanopores using the pseudospectral method of self-consistent field theory coupled with the masking technique. By varying the arm number n and the ratio τ of the linear A-block to the total A-blocks, the volume fraction of the bulk A-cylinder phase region of A­(AB) n changes in a large range even for a fixed χN = 60, allowing us to study the cases of a normal cylinder and an inverted cylinder. Our results reveal that the common phase sequence can only be maintained when the cylinder phase is not close to the boundaries of its phase region, as in the case of the pore wall attracting the B-blocks; otherwise, some structures will disappear. For example, the double-helix structure disappears when the cylinder phase is close to the cylinder/gyroid boundary. In contrast, the phase sequence becomes more robust in the case of the pore wall attracting the A-blocks. In both cases of surface preference, stable helical structures are predicted for an inverted cylinder with the volume fraction as large as f A = 0.64. For f A ≥ 0.5, the packing frustration of short B-blocks is severe, leading to a lot of astonishing distortions to many structures. Our work not only deepens the understanding on the self-assembly of block copolymers under cylindrical confinement but also provides guidance for the experimental preparation of helical structures with large volume fractions.

In this paper, we describe the fabrication of nanoparticle (NP)-embedded nanovesicles by coassembly of diblock copolymer-tethered NPs and free diblock copolymers via the dissipative particle dynamics simulation technique. We use an improved quantitative model to characterize the angular and radial distributions of NPs within vesicle walls simultaneously. In a specific circumstance, the NPs can be localized in the central portion of the vesicle walls, which is in excellent agreement with the experimental work. On the basis of this model, we find that the distributions of the NPs can be well manipulated just by three physical quantities, which are easily controlled in the experiments. For instance, the radial distributions of the NPs can be precisely controlled by changing the grafted hydrophobic chain length and the tethered arm number affects the dispersity of the NPs in the angular direction of the vesicle walls. The results provide the experimentalists with a way to design carrier-assistant drug delivery systems, which can improve the encapsulation efficiency, realize the specific targeting, and control the release of drug.

The self-assembly of block copolymers under the confinement of nanopores provides a facile way for the formation of helical nanostructures. However, these helical structures usually have a small number of helical strands, such as single or double helix. In this work, we study the self-assembly of a (B T )AB(A T )-multiblock copolymer melt under the confinement of nanopores using selfconsistent field theory, aiming to explore multi-strand helical nanostructures. Different helical structures with the number of strands ranging from 1 to 6 have been successfully predicted by tailoring the architecture of this copolymer. We find that the helical structures with an increasing number of strands are formed, accompanied by the bulk phase transition from the classical high-coordinated hexagonal cylinder phase to the low-coordinated cylinder phase (e.g., square lattice) that is controlled by the copolymer architecture. Our results further reveal that these multi-strand helical structures are mainly stabilized by the unique ability of the specific architecture to relieve the packing frustration of the majority blocks. Therefore, the formation of multi-strand helical structures is robust for AB-type block copolymers whose bulk cylinder phases are low coordinated.

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