Layered graphene oxide membranes (GOM) with densely packed sub-nanometer-wide lamellar channels show exceptional ionic and molecular transport properties. Mass and charge transport in existing materials follows their concentration gradient, whereas attaining anti-gradient transport, also called active transport, remains a great challenge. Here, we demonstrate a coupled photon-electron-ion transport phenomenon through the GOM. Upon asymmetric light illumination, cations are able to move thermodynamically uphill over a broad range of concentrations, at rates much faster than that via simple diffusion. We propose, as a plausible mechanism, that light irradiation reduces the local electric potential on the GOM following a carrier diffusion mechanism. When the illumination is applied to an off-center position, an electric potential difference is built that can drive the transport of ionic species. We further develop photonic ion switches, photonic ion diodes, and photonic ion transistors as the fundamental elements for active ion sieving and artificial photosynthesis on synthetic nanofluidic circuits.

Adsorbing small charged nanoparticles onto the outer surfaces of liposomes has become an effective strategy to stabilize liposomes against fusion prior to “seeing” target bacteria, yet allow them to fuse with the bacteria upon arrival at the infection sites. As a result, nanoparticle-stabilized liposomes have become an emerging drug delivery platform for treatment of various bacterial infections. To facilitate the translation of this platform for clinical tests and uses, herein we integrate nanoparticle-stabilized liposomes with hydrogel technology for more effective and sustained topical drug delivery. The hydrogel formulation not only preserves the structural integrity of the nanoparticle-stabilized liposomes, but also allows for controllable viscoeleasticity and tunable liposome release rate. Using Staphylococcus aureus bacteria as a model pathogen, we demonstrate that the hydrogel formulation can effectively release nanoparticle-stabilized liposomes to the bacterial culture, which subsequently fuse with bacterial membrane in a pH-dependent manner. When topically applied onto mouse skin, the hydrogel formulation does not generate any observable skin toxicity within a 7-day treatment. Collectively, the hydrogel containing nanoparticle-stabilized liposomes hold great promise for topical applications against various microbial infections.

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications.

We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~ 10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~ 75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However when the stabilized liposomes are present in an environment with neutral pH, the gold stabilizers detach from the liposomes resulting in free liposomes that can actively fuse with bacterial membranes. Using Helicobacter pylori as a model bacterium and doxycycline as a model antibiotic, we demonstrate such pH-responsive fusion activity and drug release profile of the nanoparticle-stabilized liposomes. Particularly, at neutral pH the gold nanoparticles detach and thus the doxycycline-loaded liposomes rapidly fuse with bacteria and cause superior bactericidal efficacy as compared to the free doxycycline counterpart. Our results suggest that the reported liposome system holds a substantial potential for gastric drug delivery; it remains inactive (stable) in the stomach lumen but actively interact with bacteria once reaches the mucus layer of the stomach where the bacteria may reside.