Liquid metal–polymer nano-microconjugations as an injectable and photo-activatable drug carrier†

Materials with distinct stimulus-responsive properties hold potential as carriers in next-generation drug delivery systems. In this study, we propose the design and characterisation of a carrier that can stably administer drugs, regardless of external conditions, through a two-step reaction achieved by creating a composite of materials possessing photothermal and temperature-responsive (dual-stimuli) characteristics. This composite, a novel integration of photothermal liquid metals (LMs) responsive to near-infrared laser irradiation and a temperature-responsive carboxylated polylysine-based polyampholyte, marks a significant advancement in drug delivery technology. The temperature-responsive liquid–liquid phase separation behaviour of the polymer, crucial for drug release, is precisely controlled by adjusting the ratio and concentration of the polymer anions and cations. Moreover, the heat required for phase separation and compatibility with the polymer solution is modulated through nanoparticle formation of the photothermal LMs, along with variations in the irradiation time and intensity of near-infrared laser light. Our findings, corroborated through laser microscopy and cell toxicity tests, demonstrate that this composite can generate heat upon photo-stimulation and use this heat to induce phase separation. Additionally, unlike conventional temperature-responsive carriers, this composite concentrates drugs, likely due to enhanced electrostatic interactions between the polyampholyte and the drug. This research not only overcomes the challenges faced by traditional stimulus-responsive carriers, which are influenced by the surrounding physiological environment, but also demonstrates the potential of a two-step reaction approach to concentrate and deliver drugs effectively.