Superparamagnetic iron oxide (SPIO) nanoparticles play an important role in mediating precise and effective magnetic neuro-stimulation and can help overcome limitations related to penetration depth and spatial resolution. However, nanoparticles readily diffuse in vivo, decreasing the spatial resolution and activation efficiency. In this study, we employed a microfluidic means to fabricate injectable microhydrogels encapsulated with SPIO nanoparticles, which significantly improved the stability of nanoparticles, increased the magnetic properties, and reinforced the stimulation effectivity. The fabricated magnetic microhydrogels were highly uniform in size and sphericity, enabling minimally invasive injection into brain tissue. The long-term residency in the cortex up to 22 weeks and the safety of brain tissue were shown using a mouse model. In addition, we quantitatively determined the magneto-mechanical force yielded by only one magnetic microhydrogel using a video-based method. The force was found to be within 7–8 pN under 10 Hz magnetic stimulation by both theoretical simulation and experimental measurement. Lastly, electrophysiological measurement of brain slices showed that the magnetic microhydrogels offer significant advantages in terms of neural activation relative to dissociative SPIO nanoparticles. A universal strategy is thus offered for performing magnetic neuro-stimulation with an improved prospect for biomedical translation.

Photodynamic therapy (PDT) has shown a promising capability for cancer treatment with minimal side effects. Indocyanine green (ICG), the only clinically approved near-infrared (NIR) fluorophore, has been used as a photosensitizer for PDT in clinical application. However, the main obstacle of directly utilizing ICG in the clinic lies in its low singlet oxygen (¹O₂) quantum yield (QY) and instability in aqueous solution. To improve the PDT efficacy of ICG, free ICG molecules were assembled with free oxygen nanobubbles (NBs-O₂) to fabricate ICG-NBs-O₂ by hydrophilic–hydrophobe interactions on the gas–liquid interface. Interestingly, ¹O₂ QY of ICG-NBs-O₂ solution was significantly increased to 1.6%, which was estimated to be 8 times as high as that of free ICG solution. Meanwhile, ICG-NBs-O₂ exhibited better aqueous solution stability compared with free ICG. Furthermore, through establishing tumor models in nude mice, the therapeutic efficacy of ICG-NBs-O₂ was also assessed in the PDT treatment of oral cancer. The tumor volume in ICG-NBs-O₂ treated group on day 14 decreased to 0.56 of the initial tumor size on day 1, while the tumor volume in free ICG treated group increased to 2.4 times. The results demonstrated that ICG-NBs-O₂ showed excellent tumor ablation in vivo. Therefore, this facile method provided an effective strategy for enhanced PDT treatment of ICG and showed great potential in clinical application.

With unique physicochemical properties and biological effects, magnetic nanomaterials (MNMs) play a crucial role in the biomedical field. In particular, magnetic iron oxide nanoparticles (MIONPs) are approved by the United States Food and Drug Administration (FDA) for clinical applications at present due to their low toxicity, biocompatibility, and biodegradability. Despite the unarguable effectiveness, massive space for improving such materials' performance still needs to be filled. Recently, many efforts have been devoted to improving the preparation methods based on the materials' biosafety. Besides, researchers have successfully regulated the performance of magnetic nanoparticles (MNPs) by changing their sizes, morphologies, compositions; or by aggregating as-synthesized MNPs in an orderly arrangement to meet various clinical requirements. The rise of cloud computing and artificial intelligence techniques provides novel ways for fast material characterization, automated data analysis, and mechanism demonstration. In this review, we summarized the studies that focused on the preparation routes and performance regulations of high-quality MNPs, and their special properties applied in biomedical detection, diagnosis, and treatment. At the same time, the future development of MNMs was also discussed.

Micro/nanobubbles play an essential role in ultrasound-based biomedical applications. Here, a green and simple method to fabricate micro/nanobubbles was developed by the temperature-regulated self-assembly of lipids in the presence of free bubbles. The self-assembly mechanism of lipids interacting with gas-water interfaces was investigated, and the ultrasound imaging of the obtained lipid-encapsulated bubbles (LBs) was further confirmed. Above the phase transition temperature (T_m), fluid lipids transform from vesicles to micelles, and further assemble to the free bubbles interface to be a compressed monolayer, resulting in lipid shelled microbubbles. Cooling below T_m induces the lipid shell to glassy state and stables the LBs. Moreover, increasing the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2K) content in lipids formulation can further manipulate the shell curvature and reduce the LBs size into nanobubbles. LBs with diameters of 1.68 ± 0.11 μm, 704 ± 7 nm and 208 ± 6 nm were successfully prepared. The in vitro and in vivo ultrasound imaging results showed that all of the LBs had excellent echogenicity. The nanosized LBs revealed elongated imaging duration time and greater microvascular details for the liver tissue. Avoiding the organic solvent and complicated multiple preparation process, this method has great potential in construction of various multifunctional micro/nanobubbles with size control for theranostic applications.

With superior biocompatibility and unique magnetic properties, iron-based nanoparticles (IBNP) are commonly encapsulated in cells and extracellular vesicles (EV) to allow for magnetic force controlled drug delivery and non-invasive tracking. Based on their natural source and similar morphology, we classify both cells and EVs as being natural lipid encapsulations (NLEs), distinguishing them from synthetic liposomes. Both their imaging contrast and drug effects are dominated by the amount of iron encapsulated in each NLE, demonstrating the importance of magnetic labeling efficiency. It is known that the membranes function as barriers to ensure that substances pass in and out in an orderly manner. The most important issue in increasing the cellular uptake of IBNPs is the interaction between the NLE membrane and IBNPs, which has been found to be affected by properties of the IBNPs as well as NLE heterogeneity. Two aspects are important for effective magnetic labelling: First, how to effectively drive membrane wrapping of the nanoparticles into the NLEs, and second, how to balance biosafety and nanoparticle uptake. In this review, we will provide a systematic overview of the magnetic labeling of NLEs with IBNPs. This article provides a summary of the applications of magnetically labeled NLEs and the labeling methods used for IBNPs. The review also analyzes the role of IBNPs physicochemical properties, especially their magnetic properties, and the heterogeneity of NLEs in the internalization pathway. At the same time, the future development of magnetically labeled NLEs is also discussed.

Nanomaterials are increasingly used for biomedical applications; thus, it is important to understand their biological effects. Previous studies suggested that magnetic iron oxide nanoparticles (IONPs) have tissue-repairing effects. In the present study, we explored cellular effects of IONPs in mesenchymal stem cells (MSCs) and identified the underlying molecular mechanisms. The results showed that our as-prepared IONPs were structurally stable in MSCs and promoted osteogenic differentiation of MSCs as whole particles. Moreover, at the molecular level, we compared the gene expression of MSCs with or without IONP exposure and showed that IONPs upregulated long noncoding RNA INZEB2, which is indispensable for maintaining osteogenesis by MSCs. Furthermore, overexpression of INZEB2 downregulated ZEB2, a factor necessary to repress BMP/Smad- dependent osteogenic transcription. We also demonstrated that the essential role of INZEB2 in osteogenic differentiation was ZEB2-dependent. In summary, we elucidated the molecular basis of IONPs' effects on MSCs; these findings may serve as a meaningful theoretical foundation for applications of stem cells to regenerative medicine.

The conversion of electromagnetic energy into heat by nanomagnets has the potential to be a powerful, non-invasive technique for cancer therapy by hyperthermia and hyperthermia-based drug release, while temperature controllability and targeted heating are challenges to developing applications of such magnetic inductive hyperthermia. This study was designed to control the hyperthermia position and area using a combination of alternating current (AC) and a static magnetic field. MnZn ferrite (MZF) nanoparticles which exhibited excellent hyperthermia properties were first prepared and characterized as an inductive heating mediator. We built model static magnetic fields simply using a pair of permanent magnets and studied the static magnetic field distributions by measurements and numerical simulations. The influence of the transverse static magnetic fields on hyperthermia properties was then investigated on MZF magnetic fluid, gel phantoms and SMMC-7721 cells in vitro. The results showed a static magnetic field can inhibit the temperature rise of MZF nanoparticles in an AC magnetic field. But in the uneven static magnetic field formed by a magnet pair with repelling poles face-to-face, the heating area can be restricted in a central low static field; meanwhile the side effects of hyperthermia can be reduced by a surrounding high static field. As a result we can position the hyperthermia area, protect the non-therapeutic area, and reduce the side effects just by using a well-designed combination of AC and static field.

The main phase transition temperature of a lipid membrane, which is vital for its biomedical applications such as controllable drug release, can be regulated by encapsulating hydrophobic nanoparticles into the membrane. However, the exact relationship between surface properties of the encapsulating nanoparticles and the main phase transition temperature of a lipid membrane is far from clear. In the present work, we performed coarse-grained molecular dynamics simulations to meet this end. The results show the surface roughness of nanoparticles and the density of surface-modifying molecules on the nanoparticles are responsible for the regulation. Increasing the surface roughness of the nanoparticles increases the main phase transition temperature of the lipid membrane, whereas it can be decreased in a nonlinear way via increasing the density of surface-modifying molecules on the nanoparticles. The results may provide insights for understanding recent experimental studies and promote the applications of nanoparticles in controllable drug release by regulating the main phase transition temperature of lipid vesicles.