No abstract

The circadian rhythm generates out-of-equilibrium metabolite oscillations that are controlled by feedback loops under light/dark cycles. Here we describe a non-equilibrium nanosystem comprising a binary population of enzyme-containing polymersomes capable of light-gated chemical communication, controllable feedback and coupling to macroscopic oscillations. The populations consist of esterase-containing polymersomes functionalized with photo-responsive donor–acceptor Stenhouse adducts (DASA) and light-insensitive semipermeable urease-loaded polymersomes. The DASA–polymersome membrane becomes permeable under green light, switching on esterase activity and decreasing the pH, which in turn initiates the production of alkali in the urease-containing population. A pH-sensitive pigment that absorbs green light when protonated provides a negative feedback loop for deactivating the DASA–polymersomes. Simultaneously, increased alkali production deprotonates the pigment, reactivating esterase activity by opening the membrane gate. We utilize light-mediated fluctuations of pH to perform non-equilibrium communication between the nanoreactors and use the feedback loops to induce work as chemomechanical swelling/deswelling oscillations in a crosslinked hydrogel. We envision possible applications in artificial organelles, protocells and soft robotics.

In this work, a pH-sensitive liposome-polymer nanoparticle (NP) composed of lipid, hyaluronic acid (HA) and poly(b-amino ester) (PBAE) was prepared using layer-by-layer (LbL) method for doxorubicin (DOX) targeted delivery and controlled release to enhance the cancer treatment efficacy. The NP with pH-sensitivity and targeting effect was successfully prepared by validation of charge reversal and increase of hydrodynamic diameter after each deposition of functional layer. We further showed the DOX-loaded NP had higher drug loading capacity, suitable particle size, spherical morphology, good uniformity, and high serum stability for drug delivery. We confirmed that the drug release profile was triggered by low pH with sustained release manner in vitro. Confocal microscopy research demonstrated that the NP was able to effectively target and deliver DOX into human non-small cell lung carcinoma (A549) cells in comparison to free DOX. Moreover, the blank NP showed negligible cytotoxicity, and the DOX-loaded NP could efficiently induce the apoptosis of A549 cells as well as free DOX. Notably, in vivo experiment results showed that the DOX-loaded NPs effectively inhibited the growth of tumor, enhanced the survival of tumor-bearing mice and improved the therapeutic efficacy with reduced side-effect comparing with free drug. Therefore, the NP could be a potential intelligent anticancer drug delivery carrier for cancer chemotherapy, and the LbL method might be a useful strategy to prepare multi-functional platform for drug delivery.