Inherently Fluorescent Peanut-Shaped Polymersomes for Active Cargo Transportation

Nanomotors have been extensively explored for various applications in nanomedicine, especially in cargo transportation. Motile properties enable them to deliver pharmaceutical ingredients more efficiently to the targeted site. However, it still remains a challenge to design motor systems that are therapeutically active and can also be effectively traced when taken up by cells. Here, we designed a nanomotor with integrated fluorescence and therapeutic potential based on biodegradable polymersomes equipped with aggregation-induced emission (AIE) agents. The AIE segments provided the polymersomes with autofluorescence, facilitating the visualization of cell uptake. Furthermore, the membrane structure enabled the reshaping of the AIE polymersomes into asymmetric, peanut-shaped polymersomes. Upon laser irradiation, these peanut polymersomes not only displayed fluorescence, but also produced reactive oxygen species (ROS). Because of their specific shape, the ROS gradient induced motility in these particles. As ROS is also used for cancer cell treatment, the peanut polymersomes not only acted as delivery vehicles but also as therapeutic agents. As an integrated platform, these peanut polymersomes therefore represent an interesting delivery system with biomedical potential.</p

Inherently Fluorescent Peanut-Shaped Polymersomes for Active Cargo Transportation

Nanomotors have been extensively explored for various applications in nanomedicine, especially in cargo transportation. Motile properties enable them to deliver pharmaceutical ingredients more efficiently to the targeted site. However, it still remains a challenge to design motor systems that are therapeutically active and can also be effectively traced when taken up by cells. Here, we designed a nanomotor with integrated fluorescence and therapeutic potential based on biodegradable polymersomes equipped with aggregation-induced emission (AIE) agents. The AIE segments provided the polymersomes with autofluorescence, facilitating the visualization of cell uptake. Furthermore, the membrane structure enabled the reshaping of the AIE polymersomes into asymmetric, peanut-shaped polymersomes. Upon laser irradiation, these peanut polymersomes not only displayed fluorescence, but also produced reactive oxygen species (ROS). Because of their specific shape, the ROS gradient induced motility in these particles. As ROS is also used for cancer cell treatment, the peanut polymersomes not only acted as delivery vehicles but also as therapeutic agents. As an integrated platform, these peanut polymersomes therefore represent an interesting delivery system with biomedical potential.</p

In-situ liquid phase imaging of block copolymer vesicle assembly

Amphiphilic block copolymers in aqueous solution can assemble into various ordered molecular architectures, which have a wide range of applications in, for example, drug delivery and catalytic nanoreactors.1 While sustained efforts, both experimentally and theoretically, have been made to better understand the mechanism of self- assembly in order to gain more control over this process,2, 3 there has never been a real-time, real space investigation of the assembly process on the nanoscale. Here we show the first observation of block copolymer vesicle assembly via the solvent switch protocol4 using liquid phase transmission electron microscopy (LP-TEM). We also discuss the different mechanisms of self-assembly with the ex-situ cryo-TEM observation and compare them with self-consistent field (SCF) lattice calculations. Our findings illustrate the ability of LP-TEM to implement quantitative visualization of local formation process of the block copolymer vesicles to reveal the formation mechanism on an individual particle level Please click Additional Files below to see the full abstract

Cucurbit-Like Polymersomes with Aggregation-Induced Emission Properties Show Enzyme-Mediated Motility

Polymersomes that incorporate aggregation-induced emission (AIE) moieties are attractive inherently fluorescent nanoparticles with biomedical application potential for cell/tissue imaging and tracking, as well as phototherapeutics. An intriguing feature that has not been explored yet is their ability to adopt a range of asymmetric morphologies. Structural asymmetry allows nanoparticles to be exploited as active (motile) systems. Here, we present the design and preparation of AIE fluorophore integrated (AIEgenic) cucurbit-shaped polymersome nanomotors with enzyme-powered motility. The cucurbit scaffold was constructed via morphology engineering of biodegradable fluorescent AIE-polymersomes, followed by functionalization with enzymatic machinery via a layer-by-layer (LBL) self-assembly process. Because of the enzyme-mediated decomposition of chemical fuel on the cucurbit-like nanomotor surface, enhanced directed motion was attained, when compared with the spherical counterparts. These cucurbit-shaped biodegradable AIE-nanomotors provide a promising platform for the development of active delivery systems with potential for biomedical applications

Freezing-mediated formation of supraproteins using depletion forces

Hypothesis Long-acting formulations such as microparticles, injectable depots and implantable devices can realize spatiotemporally controlled delivery of protein drugs to extend their therapeutic in vivo half-lives. To efficiently encapsulate the protein drugs into such drug delivery systems, (sub)micron-sized protein particles are needed. The formation of micronized supraproteins can be induced through the synergistic combination of attractive depletion forces and freezing. The size of the supraproteins can be fine-tuned from submicron to several microns by adjusting the ice crystallization rate through the freeze-quench depth, which is set by the target temperature. Methods Supraprotein micron structures were prepared from protein solutions under various conditions in the presence and absence of nonadsorbing polyethylene glycol. Scanning electron microscopy and dynamic light scattering were employed to determine the sizes of the supraproteins and real-time total internal reflection fluorescent microscopy was used to follow the supraprotein formation during freezing. The protein secondary structure was measured before and after micronization by circular dichroism. A phase diagram of a protein–polyethylene glycol mixture was theoretically predicted to investigate whether the depletion interaction can elucidate the phase behavior. Findings Micronized protein supraparticles could be prepared in a controlled manner by rapid freeze-drying of aqueous mixtures of bovine serum albumin, horseradish peroxidase and lysozyme mixed with polyethylene glycol. Upon freezing, the temperature quench initiates a phase separation process which is reminiscent of spinodal decomposition. This demixing is subsequently arrested during droplet phase separation to form protein-rich microstructures. The final size of the generated protein microparticles is determined by a competition between phase separation and cooling rate, which can be controlled by target temperature. The experimental phase diagram of the aqueous protein–polyethylene glycol dispersion aligns with predictions from depletion theory for charged colloids and nonadsorbing polymers.</p

Facile synthesis of rapamycin-loaded PEG-b-PLA nanoparticles and their application in immunotherapy

Poly(ethylene glycol)-block-poly(lactide) (PEG-b-PLA) micro- and nanoparticles (NPs) have been intensively investigated for applications in biomedicine, due to their inherent biocompatibility and biodegradability, which allows them to be used as sustained release systems. Current methods for preparing PEG-b-PLA NPs typically require two different steps that include polymer synthesis and NP assembly, with the necessary intermediate polymer purification and the use of a variety of organic solvents in the process. In order to facilitate the biomedical application of PEG-b-PLA NPs, it is of great interest to develop a strategy to formulate the NPs in a simplified manner. Here, we report a straightforward method to construct PEG-b-PLA NPs through a sequential two-step process without intermediate work-up, which involves synthesizing the polymer in a water-miscible organic solvent that is, N,N-dimethylformamide (DMF), followed by addition of water to the polymer solution. In this way, large NPs (~600 nm) were prepared. We comprehensively characterized the NPs using turbidity studies, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. We further demonstrated the ability of the NPs to encapsulate drugs, exemplified in the immunotherapeutic agent rapamycin, with relatively high encapsulation efficiency. In vitro drug release tests showed that rapamycin-encapsulating NPs had comparable sustained-release profiles at different pH conditions, highlighting the broad application window of our NP platform. Moreover, in vitro T cell suppression assays revealed that rapamycin-loaded NPs exhibited similar inhibitory performance to free rapamycin on CD8+ cells at all rapamycin concentrations and on CD4+ cells at high and intermediate rapamycin concentrations, while the performance of the NPs was superior on CD4+ at low rapamycin concentration. Overall, this work provides a route for the scalable synthesis of biocompatible PEG-b-PLA NPs, which can be extended to other polymeric NPs, with potential in biomedical applications such as immunotherapy.</p

Ultrafast light-activated polymeric nanomotors

Synthetic micro/nanomotors have been extensively exploited over the past decade to achieve active transportation. This interest is a result of their broad range of potential applications, from environmental remediation to nanomedicine. Nevertheless, it still remains a challenge to build a fast-moving biodegradable polymeric nanomotor. Here we present a light-propelled nanomotor by introducing gold nanoparticles (Au NP) onto biodegradable bowl-shaped polymersomes (stomatocytes) via electrostatic and hydrogen bond interactions. These biodegradable nanomotors show controllable motion and remarkable velocities of up to 125 μm s−1. This unique behavior is explained via a thorough three-dimensional characterization of the nanomotor, particularly the size and the spatial distribution of Au NP, with cryogenic transmission electron microscopy (cryo-TEM) and cryo-electron tomography (cryo-ET). Our in-depth quantitative 3D analysis reveals that the motile features of these nanomotors are caused by the nonuniform distribution of Au NPs on the outer surface of the stomatocyte along the z-axial direction. Their excellent motile features are exploited for active cargo delivery into living cells. This study provides a new approach to develop robust, biodegradable soft nanomotors with application potential in biomedicine.</p

ZSM-12 nanocrystals with tunable acidity directed by rigid diquats: Synthesis and catalytic applications

ZSM-12 is an important zeolite used as a catalyst in several industrial hydrocarbon conversion reactions. Facile synthesis of nanocrystalline ZSM-12 in a wide Si/Al compositional range remains a challenge. Here we report the successful synthesis of nanosized ZSM-12 from flexible aluminosilicate initial gels (Si/Al = 20, 50 and 100) using rigid diquaternary ammonium compounds (p-xylene-bridged bis-methylpyrrolidinium, -methylpiperidinium and −1,2-dimethylimidazolium -) as the organic structure-directing agents (OSDAs). The effective structure-directing ability of these OSDAs for nanocrystalline ZSM-12 synthesis is due to the strong interaction between the OSDA and the growing zeolite framework. The resulting nanocrystalline ZSM-12 zeolites with proper acidity exhibit substantially improved catalytic performance in hydroconversion of n-hexadecane (n-C16) and methanol-to-hydrocarbons reactions. TGA analysis of used catalysts and in situ IR spectroscopy of intra-zeolite organic species during the MTH reaction revealed that the smaller crystals result in lighter aromatics and less coke deposition due to the higher rate of desorption attributed to the larger external surface area