Cell Theranostics with Tunable Plasmonic Nanobubbles

描述（由申请人提供）：本项目将开发一种可调的治疗诊断探针，可以在单个特定细胞的一个过程中支持诊断，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，PNB不是粒子，而是一种事件（瞬态蒸汽纳米气泡），它是在针对特定细胞的金纳米粒子周围按需产生的短激光脉冲。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，并且由PNB直径确定，该PNB直径可以通过改变激发激光脉冲的能量从50 nm开始调谐。通过调节胞内PNB的尺寸和寿命，我们将实现高灵敏度成像、可控递送、选择性细胞损伤以及上述过程的光学引导。我们将实现PNB的几个特定的生物医学功能：成像具有显着（100倍和更高）提高的灵敏度和对比度，通过可控的局部破坏膜（脂质体，细胞或内体）的分子负载的交付，和细胞机械（非热）损伤与较大的PNB。在确定PNB的生物学效应机制后，我们将联合收割机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，并将提供小于一微秒持续时间的细胞治疗诊断过程。作为一种具有可调功能的隐形、按需探针，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。 公共卫生相关性：该项目旨在开发称为等离子体纳米气泡的可调设备（纳米探针），可以在细胞水平上以单一快速过程进行生物医学诊断和治疗。这种瞬态气泡是用短的单激光脉冲在金纳米颗粒周围产生的。通过动态调整它们的大小，我们将调整它们的生物学作用，从非侵入性传感到局部细胞内药物递送，以及选择性消除特定细胞。由于其独特的光学和机械性能的可调谐性，等离子体纳米气泡将通过提供新颖的通用和高效的纳米探针而影响广泛的研究、诊断、治疗和显微外科手术领域。

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.