Cell Theranostics with Tunable Plasmonic Nanobubbles

描述(申请人提供)：该项目将开发一种可调谐的治疗探头，可以在单个特定细胞中支持一个过程中的诊断、治疗和治疗指导。这将通过开发等离子体纳米气泡(PNB)来实现，这种气泡不是粒子，而是一种事件(瞬时蒸汽纳米气泡)，它是通过在针对特定细胞的金纳米颗粒周围发出短激光脉冲按需产生的。PNB的基本生物医学性质与它们的光学散射和机械冲击有关，并由PNB直径决定，PNB直径可以通过改变激发激光脉冲的能量从50 nm开始进行调节。通过调节细胞内PNB的大小和寿命，我们将实现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：显著(100倍或更高)提高灵敏度和对比度的成像，通过可控的局部破坏膜(脂质体、细胞或内体)传递分子负载，以及使用较大的PNB进行细胞机械(非热)损伤。在确定了PNB的生物学作用机制后，我们将把它的不同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。这将通过用几个激光脉冲实时调谐PNB功能来实现，并将提供持续时间不到一微秒的细胞热疗过程。作为一种具有可调功能的隐形、按需探头，PNB可以应用于所有医学领域，因为PNB机制是通用的，也可以用于检测和操纵特定分子，或用于精密显微手术。 与公共卫生相关：该项目旨在开发被称为等离子体纳米气泡的可调设备(纳米探针)，可以在细胞水平上通过单一快速过程进行生物医学诊断和治疗。这样的瞬变气泡是在金纳米颗粒周围用短的单一激光脉冲产生的。通过动态调整它们的大小，我们将调整它们的生物学行为，从非侵入性传感到局部细胞内药物输送，再到选择性地消除特定细胞。等离子体纳米气泡由于其独特的光学和机械性质的可调性，将通过提供新型的通用和高效的纳米探针而影响到广泛的研究、诊断、治疗和显微外科领域。

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.