Xiaoman Liu

Hierarchical Proteinosomes for Programmed Release of Multiple Components

A facile route to hierarchically organized multicompartmentalized proteinosomes based on a recursive Pickering emulsion procedure using amphiphilic protein-polymer nanoconjugate building blocks is described. The number of incarcerated guest proteinosomes within a single host proteinosome is controlled, and enzymes and genetic polymers encapsulated within targeted subcompartments to produce chemically organized multi-tiered structures. Three types of spatiotemporal response-retarded concomitant release, synchronous release or hierarchical release of dextran and DNA-are demonstrated based on the sequential response of the host and guest membranes to attack by protease, or through variations in the positioning of disulfide-containing cross-links in either the host or guest proteinosomes integrated into the nested architectures. Overall, our studies provide a step towards the construction of hierarchically structured synthetic protocells with chemically and spatially integrated proto-organelles.

Coordinated Membrane Fusion of Proteinosomes by Contact-Induced Hydrogel Self-Healing

Controlled membrane fusion of proteinosome-based protocells is achieved via a hydrogel-mediated process involving dynamic covalent binding, self-healing, and membrane reconfiguration at the contact interface. The rate of proteinosome fusion is dependent on dynamic Schiff base covalent interchange, and is accelerated in the presence of encapsulated glucose oxidase and glucose, or inhibited with cinnamyl aldehyde due to enzyme-mediated decreases in pH or competitive covalent binding, respectively. The coordinated fusion of the proteinosomes leads to the concomitant transportation and redistribution of entrapped payloads such as DNA and dextran. Silica colloids with amino-functionalized surfaces undergo partial fusion with the proteinosomes via a similar dynamic hydrogel-mediated mechanism. Overall, the strategy provides opportunities for the development of interacting colloidal objects, control of collective behavior in soft matter microcompartmentalized systems, and increased complexity in synthetic protocell communities.

Bio-inspired engineering proteinosomes with a cell-wall-like protective shell by self-assembly of a metal-chelated complex

A cell-wall-like shell is constructed around proteinosomes by coordination complexes of tannic acid and Fe3+, which endows the engineered proteinosomes with an enhanced Youngs modulus of the membrane, protease resistant ability, EDTA-mediated release of loaded DNA, and electrostatic gated encapsulated enzyme activity, as well as antioxidant capacity.

In situ Gelation Induced Death of Cancer Cells Based on Proteinosomes

Hydrogels are an excellent type of material that can be utilized as a platform for cell culture. However, when a bulky hydrogel forms on the inside of cancer cells, the result would be different. In this study, we demonstrate a method for in situ gelation inside cancer cells that can efficiently induce cell death. Glutathione-responsive proteinosomes with good biocompatibility were prepared as carriers for sodium alginate to be endocytosed by cancer cells, where the chelation between sodium alginate and free calcium ions in the culture medium occurs during the diffusion process. The uptake of the hydrogel-loaded proteinosomes into the cancer cells, and then the triggered release of hydrogel with concomitant aggregation, was well-confirmed by monitoring the change of the Youngs modulus of the cells based on AFM force measurements. Accordingly, when a large amount of hydrogel formed in cells, the cell viability would be inhibited by ∼90% by MTT assay at a concentration of 5.0 μM of hydrogel-loaded proteinosomes after 48 h incubation, which clearly proves the feasibility of the demonstrated method for killing cancer cells. Although more details regarding the mechanism of cell death should be conducted in the near future, such a demonstrated method of in situ gelation inside cells provides another choice for killing cancer cells.

A facile approach for the reduction of 4‑nitrophenol and degradation of congo red using gold nanoparticles or laccase decorated hybrid inorganic nanoparticles/polymer-biomacromolecules vesicles

Catalytic reduction of toxic 4‑nitrophenol to 4‑aminophenol and dye wastewater treatment over rapid, convenient gold nanoparticles or laccase decorated hybrid vesicles catalysts has attracted much attention. In current work, a stable building block was designed with inorganic gold nanoparticles and nano-conjugates; and a hybrid giant vesicles (AuNPs@vesicles) was self-assembled by using Pickering emulsion method. The vesicles were characterized by SEM, TEM, UV-vis and DLS measurements. The results showed that a temperature-responsive multifunctional building block based on BSA-PNIPAAm and gold nanoparticles was obtained. DLS results also indicated that the length of chains on the surface of AuNPs could change shorter with increasing of temperature (>32 °C) and also obtain an average diameter to ~190 nm. A substrate-rich (high concentration of 4‑nitrophenol) microenvironment can be created around AuNPs, which can dramatically accelerate the interfacial AuNPs-catalyzed reactions. The AuNPs@vesicles as catalyst in the presence of freshly prepared NaBH4 has excellent catalytic performance for reduction of 4‑nitrophenol (almost 100%). After laccase was capsulated into AuNPs@vesicles, the obtained active hybrid laccase⊂AuNPs@vesicles demonstrated high catalytic decolouration efficiency (>98.5%, nearly 2.3 times higher than that of free laccase) and excellent reusability. The possible mechanisms of reduction of 4‑nitrophenol and dye decolouration was proposed. These novel giant vesicles could provide some new opportunities in wastewater treatment, bottom-up synthetic biology, bioinspired microstorage/microreactor and drug/gene delivery.

Multifunctional and Programmable Modulated Interface Reactions on Proteinosomes

A multiresponsive microcapsule has been synthesized by incorporating photoswitchable spiropyran units and the thermoresponsive monomer N-isopropylacrylamide into membrane lumens. By using functionalized light or thermoresponsive groups, this multifunctional microcapsule can modulate programmed release and interface reactions between lipase and fluorescein diacetate, alkaline phosphatase and fluorescein diphosphate, and others. Exposing this multifunctional microcapsule in a programmed controlled way allowed us to develop schematics to understand complicated interface interactions on protocells.