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Optimizing the Geometry of Photoacoustically Active Gold Nanoparticles for Biomedical Imaging

2020, García-Álvarez, Rafaela, Chen, Lisa, Nedilko, Alexander, Sánchez-Iglesias, Ana, Rix, Anne, Lederle, Wiltrud, Pathak, Vertika, Lammers, Twan, von Plessen, Gero, Kostarelos, Kostas, Liz-Marzán, Luis M., Kuehne, Alexander J.C., Chigrin, Dmitry N.

Photoacoustics is an upcoming modality for biomedical imaging, which promises minimal invasiveness at high penetration depths of several centimeters. For superior photoacoustic contrast, imaging probes with high photothermal conversion efficiency are required. Gold nanoparticles are among the best performing photoacoustic imaging probes. However, the geometry and size of the nanoparticles determine their photothermal efficiency. We present a systematic theoretical analysis to determine the optimum nanoparticle geometry with respect to photoacoustic efficiency in the near-infrared spectral range, for superior photoacoustic contrast. Theoretical predictions are illustrated by experimental results for two of the most promising nanoparticle geometries, namely, high aspect ratio gold nanorods and gold nanostars. Copyright © 2020 American Chemical Society.

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Shelf-Life Evaluation and Lyophilization of PBCA-Based Polymeric Microbubbles

2019, Ojha, Tarun, Pathak, Vertika, Drude, Natascha, Weiler, Marek, Rommel, Dirk, Rütten, Stephan, Geinitz, Bertram, van Steenbergen, Mies J., Storm, Gert, Kiessling, Fabian, Lammers, Twan

Poly(n-butyl cyanoacrylate) microbubbles (PBCA-MB) are extensively employed for functional and molecular ultrasound (US) imaging, as well as for US-mediated drug delivery. To facilitate the use of PBCA-MB as a commercial platform for biomedical applications, it is important to systematically study and improve their stability and shelf-life. In this context, lyophilization (freeze drying) is widely used to increase shelf-life and promote product development. Here, we set out to analyze the stability of standard and rhodamine-B loaded PBCA-MB at three different temperatures (4 °C, 25 °C, and 37 °C), for a period of time of up to 20 weeks. In addition, using sucrose, glucose, polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG) as cryoprotectants, we investigated if PBCA-MB can be lyophilized without affecting their size, concentration, US signal generation properties, and dye retention. Stability assessment showed that PBCA-MB remain largely intact for three and four weeks at 4 °C and 25 °C, respectively, while they disintegrate within one to two weeks at 37 °C, thereby compromising their acoustic properties. Lyophilization analyses demonstrated that PBCA-MB can be efficiently freeze-dried with 5% sucrose and 5% PVP, without changing their size, concentration, and US signal generation properties. Experiments involving rhodamine-B loaded MB indicated that significant dye leakage from the polymeric shell takes place within two to four weeks in case of non-lyophilized PBCA-MB. Lyophilization of rhodamine-loaded PBCA-MB with sucrose and PVP showed that the presence of the dye does not affect the efficiency of freeze-drying, and that the dye is efficiently retained upon MB lyophilization. These findings contribute to the development of PBCA-MB as pharmaceutical products for preclinical and clinical applications.