因氣體對超音波具有很好的回應，微氣泡作為超音波對比劑和載體已經得到廣泛研究和應用，但其微米尺寸和不穩定的缺點限制其作為超音波診療試劑的應用。介面奈米氣泡展現出超一般氣泡的10個數量級的穩定性，對開發具有超音波的回應能力的奈米粒子系統具有重要的意義。此外，疏水材料有機會自發穩定的吸附介面奈米氣泡並增強穴蝕效應，但介面奈米氣泡是否穩定存在于疏水奈米顆粒上，目前還沒得到深入的研究。因此，本論文擬用聲學的方法證實超疏水奈米粒子表面上確實存在奈米氣泡，並基於這些介面奈米氣泡的性質，開發具有超音波回應能力的奈米粒子應用於生物醫學超音波領域。在第一章，我們回顧了當前介面奈米氣泡的研究現狀及其檢測，製備及其在生醫領域的應用。在第二章我們利用聚四氟乙烯（PTFE）奈米粒子作為疏水奈米粒子的模型，分別用聲學方法和化學方法證明其極大降低穴蝕效應的閾值間接證實疏水材料表面確實可能有介面奈米氣泡，並可持久的產生穴蝕效應並產生自由基。接著在第三章中，為確定奈米材料性質對於吸附奈米氣泡的影響，設計了不同紋理結構不同表面疏水程度的矽奈米材料為模型，並運用被動式穴蝕效應檢測和光聲高速攝像系統，超音波影像系統對其產生穴蝕效應的能力和行為進行研究。我們發現並推斷奈米粒子的外表面的疏水性質相對於其紋理結構，對其降低穴蝕效應閾值更重要。在第四章，將超疏水奈米粒子用作為氣核用超音波探在原位產生微氣泡作為超音波造影劑。最後在第五章，我們進一步將其應用於脑瘤的通透性增加，實現了注射一劑超疏水奈米粒子即可在一周內進行實現多次通透性的增强。綜上所述，我們證實了超疏水奈米粒子表面有介面奈米氣泡並穩定存在並可穩定的引發穴蝕效應產生氣泡用以超音波造影和血腦障壁開啟，使我們有機會將各種奈米材料引入並應到生物醫用超音波領域。

Microbubbles (MBs) as ultrasound (US) contrast agents and drug/gene carriers have been widely studied. However, their micron-scale size and bad stability limit their applications as theranostic agents for US. Interfacial nanobubbles (INBs) on hydrophobic surface were found to have a 10 orders of magnitude stability than traditional MBs, and are promising in developing stable US-response systems. In addition, superhydrophobic (SH) surface has the opportunity to adsorb the INBs on their surface spontaneously and to enhance the cavitation activities persistently. However, whether INBs can be stably presented on SH nanoparticles (NPs) has not been studied sufficiently. Therefore, in this study, we aimed to demonstrate that INBs can exist on the surface of SH NPs using acoustic methods and to develop US-responsible NPs for biomedical applications on the basis of their unique properties of INBs. In chapter 1, we firstly reviewed the state of art of INBs, and their detection, characterizations and applications in biomedical fields. In chapter 2, we used polytetrafluoroethylene (PTFE) NPs as a model SH NP, and applied acoustic passive cavitation detection (PCD) and chemical methods to assess the cavitation activity at various conditions. The results suggest that INBs on the PTFE NPs greatly lower the cavitation threshold and initiate durable cavitation effects and can generate free radicals. In chapter 3, we further combined various model silica NPs with the most sensitive PCD, high-speed photography and US imaging methods, to study their cavitation capability and behaviors under US. We found that the existence of INBs on the external surface of NPs were the key to explain some of their phenomena and inferred that the external SH surface of NPs plays a more dominant role in generating cavitation than their textured properties. In chapter 4, we applied above SH NPs as gas nuclei to generate MBs in-situ as US contrast agent by linear-array transducers. And in chapter 5, we further applied this SH NPs to improve the permeability of blood-tumor-barrier BTB to EB because of their durable contrast and inertial cavitation capability, and achieving the multiple successful BTB-opening within one week by US after single injection of SH NPs. In summary, we demonstrated that INBs on SH NPs were stable and can initiate cavitation and form gas bubbles for contrast enhancement and BTB-opening, which give the opportunity to serve as an theranostic agents for biomedical US.

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