Design of a Trigger‐Responsive Photothermal Vesicle‐Based Cargo Delivery Platform

Abstract Cargo delivery systems enable the targeted transport of therapeutic agents to specific sites, enhancing treatment efficacy while minimizing systemic side effects. However, many existing systems struggle with achieving precise control over the release timing. Here, a photothermal trigger‐responsive delivery platform based on Giant Unilamellar Vesicles (GUVs) functionalized with gold nanorods (GNRs) is described to overcome these challenges. Toward this end, cargo‐loaded GUVs are produced using the emulsion transfer method and effective GNR attachment to the vesicle membrane is achieved by functionalizing the GNRs with cholesterol. The near‐infrared light (NIR)‐mediated cargo release mechanism is described. Importantly, high release efficiency is achieved by optimizing the cholesterol concentration on the GNRs, which is essential for controlling the GNR attachment mechanism to the GUV membrane. Finally, GNR‐functionalized ampicillin‐loaded GUVs are tested in the presence of E. coli bacteria to demonstrate the platform's functionality. Following NIR‐triggered antibiotic release, bacterial growth is inhibited. This showcases the practical potential of the developed trigger‐responsive system. Notably, GNR‐mediated photothermal heating alone also reduces bacterial viability upon extended illumination, indicating a dual antibacterial mechanism. This versatile and biocompatible system offers a controlled delivery method with broad applicability for therapeutics, diagnostics, and other biomedical applications.