Cell Theranostics with Tunable Plasmonic Nanobubbles

项目描述（由申请人提供）：本项目将开发一种可调的治疗探针，可支持单个特定细胞的诊断，治疗和治疗指导。这将通过开发等离子体纳米泡（PNB）来实现，它不是一个粒子，而是一个事件（瞬态蒸汽纳米泡），它是在针对特定细胞的金纳米颗粒周围用短激光脉冲按需产生的。PNB的基本生物医学特性与其光学散射和机械冲击有关，并由PNB直径决定，该直径可通过改变激发激光脉冲的能量从50 nm开始调谐。通过调整细胞内PNB的尺寸和寿命，我们将实现对上述过程的高灵敏度成像、可控递送、选择性细胞损伤和光学引导。我们将实现PNB的几个特定生物医学功能：成像灵敏度和对比度显著提高（100倍或更高），通过可控的局部破坏膜（脂质体、细胞或内核体）传递分子负荷，以及使用较大的PNB进行细胞机械（非热）损伤。在确定PNB的生物学效应机制后，我们将把其不同的功能组合成一个快速序列，在单个细胞水平上提供诊断、治疗和治疗指导。这将通过使用几个激光脉冲实时调整PNB功能来实现，并将提供持续时间不到一微秒的细胞治疗过程。作为一种隐形的、按需可调的探针，PNB可以应用于医学的所有领域，因为PNB机制是通用的，也可以用于检测和操纵特定分子，或用于精确的显微手术。

DESCRIPTION (provided by applicant): This project will develop a tunable theranostic probe that can support the diagnosis, therapy and therapy guidance in one process in individual specific cells. This will be realized by developing a plasmonic nanobubble (PNB), which is not a particle but an event (transient vapor nanobubble) that is generated on-demand with a short laser pulse around gold nanoparticles targeted to specific cells. Basic biomedical properties of the PNB are related to their optical scattering and mechanical impact and are determined by the PNB diameter that can be tuned starting from 50 nm by varying the energy of the excitation laser pulse. By tuning the size and lifetime of the intracellular PNB, we will realize high-sensitive imaging, controllable delivery, selective cell damage, and optical guidance of the above processes. We will achieve several specific biomedical functions of the PNB: imaging with significantly (100-fold and higher) improved sensitivity and contrast, delivery of molecular loads through controllable localized disrupting of the membrane (of the liposome, of the cell or of the endosome), and cell mechanical (non-thermal) damage with larger PNBs. After determining the mechanisms of biological effects of the PNB, we will combine its different functions into one fast sequence to provide diagnosis, treatment and treatment guidance at the individual cell level. This will be achieved by real-time tuning of the PNB function with several laser pulses and will deliver a cell theranostic process of less than one microsecond duration. Being a stealth, on-demand probe with tunable function, the PNB can be applied to all areas of medicine since the PNB mechanism is universal and can also be employed for detecting and manipulating specific molecules, or for precise microsurgery. PUBLIC HEALTH RELEVANCE: This project is aimed at the development of tunable devices (nanoprobes) called plasmonic nanobubbles that can carry out biomedical diagnosis and therapy in a single fast process at cell level. Such transient bubbles are generated around gold nanoparticles with a short single laser pulse. By tuning dynamically their size we will tune their biological action from a non-invasive sensing, to localized intracellular drug delivery, and to selective elimination of specific cells. Due to their unique tunability of optical and mechanical properties, plasmonic nanobubbles will impact wide areas of research, diagnosis, therapy and micro-surgery by providing the novel universal and efficient nanoprobe.