Investigation of the enhanced antitumour potency of STING agonist after conjugation to polymer nanoparticles.

Intravenously administered cyclic dinucleotides and other STING agonists are hampered by low cellular uptake and poor circulatory half-life. Here we report the covalent conjugation of cyclic dinucleotides to poly(ß-amino ester) nanoparticles through a cathepsin-sensitive linker. This is shown to increase stability and loading, thereby expanding the therapeutic window in multiple syngeneic tumour models, enabling the study of how the long-term fate of the nanoparticles affects the immune response. In a melanoma mouse model, primary tumour clearance depends on the STING signalling by host cells-rather than cancer cells-and immune memory depends on the spleen. The cancer cells act as a depot for the nanoparticles, releasing them over time to activate nearby immune cells to control tumour growth. Collectively, this work highlights the importance of nanoparticle structure and nano-biointeractions in controlling immunotherapy efficacy.

Imine and metal-ligand dynamic bonds in soft polymers for autonomous self-healing capacitive-based pressure sensors.

In this work, a facile and simple yet effective method to generate intrinsic autonomous self-healing polymers was developed, leading to new materials that can be easily fine-tuned both mechanically and chemically. The new materials were designed to incorporate two dynamic and reversible types of chemical bonds, namely dynamic imine and metal-coordinating bonds, to enable autonomous self-healing, controlled degradability and ultra-high tunable stretchability (up to 800% strain) based on the ratio of metal to ligand incorporated. Through an easy condensation reaction, imine bonds are generated at the end-termini of a short siloxane chain. The new dynamic system was characterized by a variety of techniques, including tensile-pull strain testing, atomic force microscopy and UV-Vis spectroscopy, which showed that the highly dynamic imine bonds, combined with coordination with Fe2+ ions, allow for the material to regenerate 88% of its mechanical strength after physical damage. The materials were also controlled to be degraded in mild acidic conditions. Lastly, application in self-healable electronics was demonstrated through the fabrication of a capacitive-based pressure sensor, which shows good sensitivity and dynamic response (∼0.33 kPa-1) before and after healing.