Imaging Laser-Triggered Drug Release from Gold Nanocages with Transient Absorption Lifetime Microscopy

Nanoparticles have shown promise in loading and delivering drugs for targeted therapy. Many progresses have been made in the design, synthesis, and modification of nanoparticles to fulfill such goals. However, realizing targeted intracellular delivery and controlled release of drugs remains challenging, partly because of the lack of reliable tools to detect the drug-releasing process. In this paper, we applied femtosecond laser pulses to trigger the explosion of gold nanocages (AuNCs) and control the intracellular release of loaded aluminum phthalocyanine (AlPcS) molecules for photodynamic therapy (PDT). AuNCs were found to enhance the encapsulation efficiency and suppress the PDT effect of AlPcS molecules until they were released. More importantly, we discovered that the excited-state lifetimes of the AlPcS-AuNC conjugate (∼3 ps) and free AlPcS (∼11 ps) differ significantly, which was utilized to image the released drug molecules using transient absorption lifetime microscopy with the same laser source. This technique extracts information similar to fluorescence lifetime imaging microscopy but is superior in imaging the molecules that hardly fluoresce or are prone to photobleaching. We further combined a dual-phase lock-in detection technique to show the potential of real-time imaging based on the change in transient optical behaviors. Our method may provide a new tool for investigating nanoparticle-assisted drug delivery and release.