Ultrasound is a widely-used imaging modality in clinics as a low-cost, non-invasive, non-radiative procedure allowing therapists faster decision-making. Microbubbles have been used as ultrasound contrast agents for decades, while recent attention has been attracted to consider them as stimuli-responsive drug delivery systems. Pioneering microbubbles were Albunex with a protein shell composed of human serum albumin, which entered clinical practice in 1993. However, current research expanded the set of proteins for a microbubble shell beyond albumin and applications of protein microbubbles beyond ultrasound imaging. Hence, this review summarizes all-known protein microbubbles over decades with a critical evaluation of formulations and applications to optimize the safety (low toxicity and high biocompatibility) as well as imaging efficiency. We provide a comprehensive overview of (1) proteins involved in microbubble formulation, (2) peculiarities of preparation of protein stabilized microbubbles with consideration of large-scale production, (3) key chemical factors of stabilization and functionalization of protein-shelled microbubbles, and (4) biomedical applications beyond ultrasound imaging (multimodal imaging, drug/gene delivery with attention to anticancer treatment, antibacterial activity, biosensing). Presented critical evaluation of the current state-of-the-art for protein microbubbles should focus the field on relevant strategies in microbubble formulation and application for short-term clinical translation. Thus, a protein bubble-based platform is very perspective for theranostic application in clinics.

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We developed a novel asymmetric depth filtration (DF) approach to isolate extracellular vesicles (EVs) from biological fluids that outperforms ultracentrifugation and size‐exclusion chromatography in purity and yield of isolated EVs. By these metrics, a single‐step DF matches or exceeds the performance of multistep protocols with dedicated purification procedures in the isolation of plasma EVs. We demonstrate the selective transit and capture of biological nanoparticles in asymmetric pores by size and elasticity, low surface binding to the filtration medium, and the ability to cleanse EVs held by the filter before their recovery with the reversed flow all contribute to the achieved purity and yield of preparations. We further demonstrate the method's versatility by applying it to isolate EVs from different biofluids (plasma, urine, and cell culture growth medium). The DF workflow is simple, fast, and inexpensive. Only standard laboratory equipment is required for its implementation, making DF suitable for low‐resource and point‐of‐use locations. The method may be used for EV isolation from small biological samples in diagnostic and treatment guidance applications. It can also be scaled up to harvest therapeutic EVs from large volumes of cell culture medium.

Hybrid multimodal nanoparticles, applicable simultaneously to the noninvasive imaging and therapeutic treatment, are highly demanded for clinical use. Here, Fe-Au core-satellite nanoparticles prepared by the method of pulsed laser ablation in liquids were evaluated as dual magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and as sensitizers for laser-induced hyperthermia of cancer cells. The biocompatibility of Fe-Au nanoparticles was improved by coating with polyacrylic acid, which provided excellent colloidal stability of nanoparticles with highly negative ζ-potential in water (−38 ± 7 mV) and retained hydrodynamic size (88 ± 20 nm) in a physiological environment. The ferromagnetic iron cores offered great contrast in MRI images with r2 = 11.8 ± 0.8 mM−1 s−1 (at 1 T), while Au satellites showed X-ray attenuation in CT. The intravenous injection of nanoparticles enabled clear tumor border visualization in mice. Plasmonic peak in the Fe-Au hybrids had a tail in the near-infrared region (NIR), allowing them to cause hyperthermia under 808 nm laser exposure. Under NIR irradiation Fe-Au particles provided 24.1 °C/W heating and an IC50 value below 32 µg/mL for three different cancer cell lines. Taken together, these results show that laser synthesized Fe-Au core-satellite nanoparticles are excellent theranostic agents with multimodal imaging and photothermal capabilities.

In article number https://doi.org/10.1002/adhm.201700818, Gleb B. Sukhorukov and co‐workers present a fresh outlook on the advance in the design of cell‐based drug vehicles as a biological transporter platform for targeted delivery of different drugs. An overview of the current strategies of cell functionalization by nano‐ and microcarriers are provided for the first time. Authors also discuss animal models for studying cell assisted drug delivery. The cover image represents cells carrying the nanoparticles across the blood vessel wall to the inflammation site, where therapeutic nanoparticles are then released. Cover illustration by Jessica A. Vasserman.