State Key Laboratory of Surface Physics and Department of Physics, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Collaborative Innovation Center of Genetics and Development, Fudan University , Shanghai 200433, China.
ACS Appl Mater Interfaces. 2017 Jun 14;9(23):19653-19661. doi: 10.1021/acsami.7b04758. Epub 2017 Jun 5.
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.
纳米颗粒在负载和输送药物用于靶向治疗方面显示出了巨大的潜力。为了实现这些目标，人们在纳米颗粒的设计、合成和修饰方面取得了许多进展。然而，实现药物的靶向细胞内输送和控制释放仍然具有挑战性，部分原因是缺乏可靠的工具来检测药物释放过程。在本文中，我们应用飞秒激光脉冲触发金纳米笼（AuNCs）的爆炸，控制负载的铝酞菁（AlPcS）分子的细胞内释放，用于光动力治疗（PDT）。结果发现，AuNCs 可以提高 AlPcS 分子的包封效率并抑制其 PDT 效应，直到它们被释放。更重要的是，我们发现 AlPcS-AuNC 缀合物（∼3 ps）和游离 AlPcS（∼11 ps）的激发态寿命有显著差异，这被用来使用具有相同激光源的瞬态吸收寿命显微镜对释放的药物分子进行成像。该技术提取的信息类似于荧光寿命成像显微镜，但在成像几乎不发荧光或容易光漂白的分子方面具有优势。我们进一步结合双相锁相检测技术，展示了基于瞬态光学行为变化的实时成像的潜力。我们的方法可能为研究纳米颗粒辅助药物输送和释放提供一种新的工具。
