Barmin Roman A, Rudakovskaya Polina G, Gusliakova Olga I, Sindeeva Olga A, Prikhozhdenko Ekaterina S, Maksimova Elizaveta A, Obukhova Ekaterina N, Chernyshev Vasiliy S, Khlebtsov Boris N, Solovev Alexander A, Sukhorukov Gleb B, Gorin Dmitry A
Skolkovo Institute of Science and Technology, 3 Nobelya Str., 121205 Moscow, Russia.
Remote Controlled Theranostic Systems Lab, Saratov State University, 83 Astrakhanskaya Str., 410012 Saratov, Russia.
Nanomaterials (Basel). 2021 Feb 6;11(2):415. doi: 10.3390/nano11020415.
Microbubbles have already reached clinical practice as ultrasound contrast agents for angiography. However, modification of the bubbles' shell is needed to produce probes for ultrasound and multimodal (fluorescence/photoacoustic) imaging methods in combination with theranostics (diagnostics and therapeutics). In the present work, hybrid structures based on microbubbles with an air core and a shell composed of bovine serum albumin, albumin-coated gold nanoparticles, and clinically available photodynamic dyes (zinc phthalocyanine, indocyanine green) were shown to achieve multimodal imaging for potential applications in photodynamic therapy. Microbubbles with an average size of 1.5 ± 0.3 μm and concentration up to 1.2 × 10 microbubbles/mL were obtained and characterized. The introduction of the dye into the system reduced the solution's surface tension, leading to an increase in the concentration and stability of bubbles. The combination of gold nanoparticles and photodynamic dyes' influence on the fluorescent signal and probes' stability is described. The potential use of the obtained probes in biomedical applications was evaluated using fluorescence tomography, raster-scanning optoacoustic microscopy and ultrasound response measurements using a medical ultrasound device at the frequency of 33 MHz. The results demonstrate the impact of microbubbles' stabilization using gold nanoparticle/photodynamic dye hybrid structures to achieve probe applications in theranostics.
微泡作为用于血管造影的超声造影剂已进入临床实践。然而，需要对气泡外壳进行修饰，以制备用于超声以及与治疗诊断学（诊断与治疗）相结合的多模态（荧光/光声）成像方法的探针。在本研究中，基于具有空气核心和由牛血清白蛋白、白蛋白包被的金纳米颗粒以及临床可用的光动力染料（锌酞菁、吲哚菁绿）组成的外壳的微泡的混合结构，被证明可实现多模态成像，用于光动力治疗的潜在应用。获得了平均尺寸为1.5±0.3μm且浓度高达1.2×10个微泡/毫升的微泡并对其进行了表征。将染料引入系统降低了溶液的表面张力，导致气泡浓度和稳定性增加。描述了金纳米颗粒和光动力染料对荧光信号和探针稳定性的综合影响。使用荧光断层扫描、光栅扫描光声显微镜以及使用频率为33MHz的医用超声设备进行超声响应测量，评估了所得探针在生物医学应用中的潜在用途。结果表明，使用金纳米颗粒/光动力染料混合结构对微泡进行稳定化处理，对实现探针在治疗诊断学中的应用具有重要影响。
