Drug carriers based on polyelectrolyte microcapsules remotely controlled with an external magnetic field are a promising drug delivery system. However, the influence of capsule parameters on microcapsules’ behavior in vivo is still ambiguous and requires additional study. Here, we discuss how the processes occurring in the blood flow influence the circulation time of magnetic polyelectrolyte microcapsules in mouse blood after injection into the blood circulatory system and their interaction with different blood components, such as WBCs and RBCs. The investigation of microcapsules ranging in diameter 1–5.5 $\mathsf{\mu }$m allowed us to reveal the dynamics of their filtration by vital organs, cytotoxicity, and hemotoxicity, which is dependent on their size, alongside the efficiency of their interaction with the magnetic field. Our results show that small capsules have a long circulation time and do not affect blood cells. In contrast, the injection of large 5.5 $\mathsf{\mu }$m microcapsules leads to fast filtration from the blood flow, induces the inhibition of macrophage cell line proliferation after 48 h, and causes an increase in hemolysis, depending on the carrier concentration. The obtained results reveal the possible directions of fine-tuning microcapsule parameters, maximizing capsule payload without the side effects for the blood flow or the blood cells.

Gold nanoparticles are widely used in laser biomedical applications due to their favorable properties, mainly localized plasmon resonance. However, laser radiation can cause a change in the shape and size of plasmonic nanoparticles, thus resulting in an unwanted reduction of their photothermal and photodynamic efficiency due to a drastic alteration of optical properties. Most previously reported experiments were carried out with bulk colloids where different particles were irradiated by different numbers of laser pulses, thus making it difficult to accurately evaluate the laser power photomodification (PM) threshold. Here, we examine the one-shot nanosecond laser-pulse PM of bare and silica-coated gold nanoparticles moving in a capillary flow. Four types of gold nanoparticles, including nanostars, nanoantennas, nanorods, and SiO₂@Au nanoshells, were fabricated for PM experiments. To evaluate the changes in the particle morphology under laser irradiation, we combine measurements of extinction spectra with electron microscopy. A quantitative spectral approach is developed to characterize the laser power PM threshold in terms of normalized extinction parameters. The experimentally determined PM threshold increases in series were as follows: nanorods, nanoantennas, nanoshells, and nanostars. An important observation is that even a thin silica shell significantly increases the photostability of gold nanorods. The developed methods and reported findings can be useful for the optimal design of plasmonic particles and laser irradiation parameters in various biomedical applications of functionalized hybrid nanostructures.

Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are of great interest for modern diagnostics, but devices that can solve this problem for the whole blood volume of laboratory animals are still rare. Here we have developed SPIM-based lightsheet flow cytometer for the detection of fluorescently-labeled objects in whole blood. The bypass channel between two blood vessels connected with the external flow cell was used to visualize, detect, and magnetically separate fluorescently-labeled objects without hydrodynamic focusing. Carriers for targeted drug delivery were used as model objects to test the device performance. They were injected into the bloodstream of the rat, detected fluorescently, and then captured from the bloodstream by a magnetic separator prior to filtration in organs. Carriers extracted from the whole blood were studied by a number of in vitro methods.

A promising approach to targeted drug delivery is the remote control of magnetically sensitive objects using an external magnetic field source. This method can assist in the accumulation of magnetic carriers in the affected area for local drug delivery, thus providing magnetic nanoparticles for MRI contrast and magnetic hyperthermia, as well as the magnetic separation of objects of interest from the bloodstream and liquid biopsy samples. The possibility of magnetic objects’ capture in the flow is determined by the ratio of the magnetic field strength and the force of viscous resistance. Thus, the capturing ability is limited by the objects’ magnetic properties, size, and flow rate. Despite the importance of a thorough investigation of this process to prove the concept of magnetically controlled drug delivery, it has not been sufficiently investigated. Here, we studied the efficiency of polyelectrolyte capsules’ capture by the external magnetic field source depending on their size, the magnetic nanoparticle payload, and the suspension’s flow rate. Additionally, we estimated the possibility of magnetically trapping cells containing magnetic capsules in flow and evaluated cells’ membrane integrity after that. These results are required to prove the possibility of the magnetically controlled delivery of the encapsulated medicine to the affected area with its subsequent retention, as well as the capability to capture magnetically labeled cells in flow.

In vivo liquid biopsy, especially using the photoacoustic (PA) method, demonstrated high clinical potential for early diagnosis of deadly diseases such as cancer, infections, and cardiovascular disorders through the detection of rare circulating tumor cells (CTCs), bacteria, and clots in the blood background. However, little progress has been made in terms of standardization of these techniques, which is crucial to validate their high sensitivity, accuracy, and reproducibility. In the present study, we addressed this important demand by introducing a dynamic blood vessel phantom with flowing mimic normal and abnormal cells. The light transparent silica microspheres were used as white blood cells and platelets phantoms, while hollow polymeric capsules, filled with hemoglobin and melanin, reproduced red blood cells and melanoma CTCs, respectively. These phantoms were successfully used for calibration of the PA flow cytometry platform with high-speed signal processing. The results suggest that these dynamic cell flow phantoms with appropriate biochemical, optical, thermal, and acoustic properties can be promising for the establishment of standardization tool for calibration of PA, fluorescent, Raman, and other detection methods of in vivo flow cytometry and liquid biopsy.