Polina G. Rudakovskaya

Doxorubicin is an anthracycline-class medication with a broad spectrum of antitumor activity, although significant adverse cardiac toxicity limits its use. This dictates the need for its encapsulation in drug delivery systems, as nanoparticles can eliminate cardiac toxicity and enhance tumor uptake. This review focuses on advances in inorganic/polymeric nanocarrier engineering that can (1) provide sites for doxorubicin immobilization, (2) ensure colloidal stability, and (3) allow multifunctional capabilities for synergistic cancer treatment. Focusing mainly on polymeric and polymer-capped inorganic nanomaterials owing to their high control over composition, we describe approaches to obtain nanoparticles for synergistic chemotherapy using doxorubicin in combination with magnetic hyperthermia, photothermal, and photodynamic cancer therapies. In addition, the review outlines selected chemical routes for the synthesis of the macromolecules required for efficient doxorubicin incorporation. The prospects for the use of doxorubicin carriers as theranostics described in this review underscore the need for innovation in carrier design for efficient cancer therapy.

Background : Infertility is a major global health concern, with fallopian tube blockages contributing to up to 35% of female infertility cases, and highlighting the critical need for effective tubal patency diagnostics. Hysterosalpingo‐contrast sonography (HyCoSy) is a noninvasive ultrasound technique for assessing fallopian tube patency, crucial in infertility diagnostics. Despite its advantages over x‐ray and laparoscopic methods, its clinical use is limited due to operator dependence and the need for specialized training. However, existing ultrasound phantoms lack compatibility with microbubble‐based contrast agents, restricting their effectiveness for HyCoSy training. Purpose : This study presents a low‐cost, anatomically representative ultrasound phantom of the female reproductive system designed to support contrast agent infusion. Methods : The phantom replicates the uterus and fallopian tubes using tissue‐mimicking materials with acoustic and mechanical properties approximating human muscle and serous membrane tissues. Fabrication was performed using 3D‐printed molds. Materials were selected and characterized based on density, Young's modulus, acoustic velocity, and attenuation slope, and compared with literature‐reported physiological ranges. Reproducibility was assessed through multiple independent fabrications, and statistical analysis was conducted to evaluate inter‐batch variability. Results : Among 15 tested material formulations, muscle‐mimicking sample 6 exhibited a Young's modulus of 24.3 ± 4.8 kPa, an acoustic velocity of 1550 ± 5 m/s, and an attenuation slope of 0.055 ± 0.002 dB/mm/MHz—closely matching reported values for human muscle tissue (13–32 kPa, 1547 m/s, 0.05–0.054 dB/mm/MHz, respectively). Serosa‐mimicking sample 15 showed a Young's modulus of 60.7 ± 7.3 kPa, velocity of 1598 ± 5 m/s, and attenuation slope of 0.079 ± 0.002 dB/mm/MHz, closely aligning with reported ranges for serous tissue (50–500 kPa, 1575–1595 m/s, 0.048–0.157 dB/mm/MHz). Computed tomography and B‐mode ultrasound confirmed the structural integrity and formation of internal cavities in the phantom, while fluorescence and ultrasound imaging demonstrated effective retention of contrast agents during microbubble infusion. Both B‐mode and non‐linear contrast ultrasound imaging enabled clear visualization of the uterine and tubal structures. Conclusions : The phantom demonstrates validated mechanical and acoustic properties that closely match those of human muscle and serosa, supporting its suitability for illustrating core principles of HyCoSy, including contrast agent infusion and tubal visualization. The low cost and structural reproducibility of the model make it a practical option for simulation‐based radiology training.

Microbubbles are routinely used ultrasound contrast agents in the clinic. While a soft protein shell is commercially preferable for imaging purposes, a rigid polymer shell demonstrates prolonged agent stability. Hence, combining polymers and proteins in one shell composition can advance microbubble properties. We formulated the hybrid "protein-copolymer" microbubble shell with a complex of bovine serum albumin and an amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid. The resulting microbubbles demonstrated advanced physicochemical and acoustic properties, preserving in vitro biocompatibility. Adjusting the mass ratio between protein and copolymer allowed fine tuning of the microbubble properties of concentration (by two orders, up to 10¹⁰ MBs/mL), mean size (from 0.8 to 5 μm), and shell thickness (from 28 to 50 nm). In addition, the minimum air-liquid surface tension for the "protein-copolymer" solution enabled the highest bubble concentration. At the same time, a higher copolymer amount in the bubble shell increased the bubble size and tuned duration and intensity of the contrast during an ultrasound procedure. Demonstrated results exemplify the potential of the hybrid "protein-polymer" microbubble shell, allowing tailoring of microbubble properties for image-guided applications, combining advances of each material involved in the formulation.

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.

Surface-enhanced Raman spectroscopy (SERS) is a powerful technique for biosensing. However, SERS analysis has several concerns: the signal is limited by a number of molecules and the area of the plasmonic substrate in the laser hotspot, and quantitative analysis in a low-volume droplet is confusing due to the change of concentration during quick drying. The usage of hollow-core microstructured optical fibers (HC-MOFs) is thought to be an effective way to improve SERS sensitivity and limit of detection through the effective irradiation of a small sample volume filling the fiber capillaries. In this paper, we used layer-by-layer assembly as a simple method for the functionalization of fiber capillaries by gold nanoparticles (seeds) with a mean diameter of 8 nm followed by UV-induced chloroauric acid reduction. We also demonstrated a simple and quick technique used for the analysis of the SERS platform formation at every stage through the detection of spectral shifts in the optical transmission of HC-MOFs. The enhancement of the Raman signal of a model analyte Rhodamine 6G was obtained using such type of SERS platform. Thus, a combination of nanostructured gold coating as a SERS-active surface and a hollow-core fiber as a microfluidic channel and a waveguide is perspective for point-of-care medical diagnosis based on liquid biopsy and exhaled air analysis.

Gaseous oxygen plays a vital role in driving the metabolism of living organisms and has multiple agricultural, medical, and technological applications. Different methods have been discovered to produce oxygen, including plants, oxygen concentrators and catalytic reactions. However, many such approaches are relatively expensive, involve challenges, complexities in post-production processes or generate undesired reaction products. Catalytic oxygen generation using hydrogen peroxide is one of the simplest and cleanest methods to produce oxygen in the required quantities. Chemically powered micro/nanomotors, capable of self-propulsion in liquid media, offer convenient and economic platforms for on-the-fly generation of gaseous oxygen on demand. Micromotors have opened up opportunities for controlled oxygen generation and transport under complex conditions, critical medical diagnostics and therapy. Mobile oxygen micro-carriers help better understand the energy transduction efficiencies of micro/nanoscopic active matter by careful selection of catalytic materials, fuel compositions and concentrations, catalyst surface curvatures and catalytic particle size, which opens avenues for controllable oxygen release on the level of a single catalytic microreactor. This review discusses various micro/nanomotor systems capable of functioning as mobile oxygen generators while highlighting their features, efficiencies and application potentials in different fields.