Magnetic particle image scanner based on asymmetric core-filled electromagnetic actuator.

Monitoring the distribution of magnetic nanoparticles (MNPs) in the vascular system is an important task for the advancement of precision therapeutics and drug delivery. Despite active targeting using active motilities, it is required to visualize the position and concentration of carriers that reach the target, to promote the development of this technology. In this work, a feasibility study is presented on a tomographic scanner that allows monitoring of the injected carriers quantitatively in a relatively short interval. The device is based on a small-animal-scale asymmetric magnetic platform integrated with magnetic particle imaging technology. An optimized isotropic field-free region (FFR) generation method using a magnetic manipulation system (MMS) is derived and numerically investigated. The in-vitro and in-vivo tracking performances are demonstrated with a high position accuracy of approximately 1 mm. A newly proposed tracking method was developed, specialized in vascular system, with quick scanning time (about 1s). In this paper, the primary function of the proposed system is to track magnetic particles using a magnetic manipulation system. Through this, proposed method enables the conventional magnetic actuation systems to upgrade the functionalities of both manipulation and localization of magnetic objects.

Sonazoid-Conjugated Natural Killer Cells for Tumor Therapy and Real-Time Visualization by Ultrasound Imaging.

Various cell therapy strategies, including chimeric antigen receptor-expressing T or natural killer (NK) cells and cell-mediated drug delivery, have been developed for tumor eradication. However, the efficiency of these strategies against solid tumors remains unclear. We hypothesized that real-time control and visualization of therapeutic cells, such as NK cells, would improve their therapeutic efficacy against solid tumors. In this study, we engineered Sonazoid microbubble-conjugated NK (NK_Sona) cells and demonstrated that they were detectable by ultrasound imaging in real-time and maintained their functions. The Sonazoid microbubbles on the cell membrane did not affect the cytotoxicity and viability of the NK cells in vitro. Additionally, the NK_Sona cells could be visualized by ultrasound imaging and inhibited tumor growth in vivo. Taken together, our findings demonstrate the feasibility of this new approach in the use of therapeutic cells, such as NK cells, against solid tumors.

Guide-Wired Helical Microrobot for Percutaneous Revascularization in Chronic Total Occlusion in-Vivo Validation.

OBJECTIVE: For the revascularization in small vessels such as coronary arteries, we present a guide-wired helical microrobot mimicking the corkscrew motion for mechanical atherectomy that enables autonomous therapeutics and minimizing the radiation exposure to clinicians. METHODS: The microrobot is fabricated with a spherical joint and a guidewire. A previously developed external electromagnetic manipulation system capable of high power and frequency is incorporated and an autonomous guidance motion control including driving and steering is implemented in the prototype. We tested the validity of our approach in animal experiments under clinical settings. For the in vivo test, artificial thrombus was fabricated and placed in a small vessel and atherectomy procedures were conducted. RESULTS: The devised approach enables us to navigate the helical robot to the target area and successfully unclog the thrombosis in rat models in vivo. CONCLUSION: This technology overcomes several limitations associated with a small vessel environment and promises to advance medical microrobotics for real clinical applications while achieving intact operation and minimizing radiation exposures to clinicians. SIGNIFICANCE: Advanced microrobot based on multi-discipline technology could be validated in vivo for the first time and that may foster the microrobot application at clinical sites.

Multifunctional Nanorobot System for Active Therapeutic Delivery and Synergistic Chemo-photothermal Therapy.

Nanorobots are safe and exhibit powerful functionalities, including delivery, therapy, and diagnosis. Therefore, they are in high demand for the development of new cancer therapies. Although many studies have contributed to the progressive development of the nanorobot system for anticancer drug delivery, these systems still face some critical limitations, such as potentially toxic materials in the nanorobots, unreasonable sizes for passive targeting, and the lack of several essential functions of the nanorobot for anticancer drug delivery including sensing, active targeting, controlling drug release, and sufficient drug loading capacity. Here, we developed a multifunctional nanorobot system capable of precise magnetic control, sufficient drug loading for chemotherapy, light-triggered controlled drug release, light absorption for photothermal therapy, enhanced magnetic resonance imaging, and tumor sensing. The developed nanorobot system exhibits an in vitro synergetic antitumor effect of photothermal therapy and chemotherapy and outstanding tumor-targeting efficiency in both in vitro and in vivo environments. The results of this study encourage further explorations of an efficient active drug delivery system for cancer treatment and the development of nanorobot systems for other biomedical applications.

Fabrication and biological properties of calcium phosphate/chitosan composite coating on titanium in modified SBF.

In order to increase the biocompatibility and bioactivity of chitosan, hydroxyapatite was in situ combined into the spin-coated chitosan layer on the titanium substrate by incubating in modified simulated body fluid (m-SBF). The calcium phosphate/chitosan (CaP/CS) composite prepared in m-SBF showed a homogeneous distribution of spherical nano-clusters. The hydrophilicity of the coatings was increased by performing NaOH post-treatment of CaP/CS composites, which also affected apatite formation. Biocompatibility of the coatings was assessed by investigating the cellular response of human osteoblast-like MG-63 cells with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell adhesion and osteogenic properties of the mesoporous CaP/CS composite were evaluated by SEM and ALPase assay, respectively. This in vitro study showed improved cell adhesion and differentiation on nanostructured CaP/CS composites. These results indicate that this CaP/CS composite could be a promising candidate for bone tissue engineering.

Cardiovascular and arousal responses to single-lumen endotracheal and double-lumen endobronchial intubation in the normotensive and hypertensive elderly.

BACKGROUND: Endotracheal intubation usually causes transient hypertension and tachycardia. The cardiovascular and arousal responses to endotracheal and endobronchial intubation were determined during rapid-sequence induction of anesthesia in normotensive and hypertensive elderly patients. METHODS: Patients requiring endotracheal intubation with (HT, n = 30) or without hypertension (NT, n = 30) and those requiring endobronchial intubation with (HB, n = 30) or without hypertension (NB, n = 30) were included in the study. Anesthesia was induced with intravenous thiopental 5 mg/kg followed by succinylcholine 1.5 mg/kg. After intubation, all subjects received 2% sevoflurane in 50% nitrous oxide and oxygen. Mean arterial pressure (MAP), heart rate (HR), plasma catecholamine concentration, and Bispectral Index (BIS) values, were measured before and after intubation. RESULTS: The intubation significantly increased MAP, HR, BIS values and plasma catecholamine concentrations in all groups, the peak value of increases was comparable between endotracheal and endobronchial intubation. However, pressor response persisted longer in the HB group than in the HT group (5.1 ± 1.6 vs. 3.2 ± 0.9 min, P < 0.05). The magnitude of increases in MAP and norepinephrine from pre-intubation values was greater in the hypertensive than in the normotensive group (P < 0.05), while there were no differences in those of HR and BIS between the hypertensive and normotensive groups. CONCLUSIONS: Cardiovascular response and arousal response, as measured by BIS, were similar in endobronchial and endotracheal intubation groups regardless of the presence or absence of hypertension except for prolonged pressor response in the HB group. However, the hypertensive patients showed enhanced cardiovascular responses than the normotensive patients.

Evaluation of interaction between intrathecal adenosine and MK801 or NBQX in a rat formalin pain model.

Adenosine and excitatory amino acids have been known to be involved in modulating nociceptive transmission at the spinal level. The authors assessed the characteristics of the interaction of the adenosine-excitatory amino acid antagonist combinations in the spinal cord of rats on the formalin-induced nociception. Intrathecal NMDA antagonist ((5R, 10S)-(+)-5-methyl-10,11-dihydro-(5)H-dibenzo[a[,]d]cyclohepten-5,10-imine hydrogen maleate, MK801, 30 microg) and AMPA antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[F]quinoxaline-7-sulfonamide, NBQX, 3 microg) decreased the total number of flinches during both phases in the formalin test. Intrathecal adenosine (300 microg) had little effect on the phase 1 flinching response, but decreased the phase 2 response. The fixed dose analysis and the isobolographic analysis revealed that adenosine interacts additively with MK801 and NBQX in the spinal cord.

Lack of the nitric oxide-cyclic GMP-potassium channel pathway for the antinociceptive effect of intrathecal zaprinast in a rat formalin test.

Zaprinast is a phosphodiesterase inhibitor that is active in various models of pain when administered locally. In addition, the antinociception of zaprinast is involved in the nitric oxide (NO)-cGMP pathway. However, the effect of zaprinast administered spinally has not been examined. Therefore, this study examined the effect of zaprinast on the formalin-induced nociception at the spinal level. Next, the role of the NO-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Catheters were inserted into the intrathecal space of male Sprague-Dawley (SD) rats. Pain was induced by applying 50 microl of a 5% formalin solution to the hindpaw. The change in the zaprinast-induced effect was examined after an intrathecal pretreatment with a NO synthase inhibitor (l-NMMA), a guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide). Zaprinast produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Intrathecal l-NMMA, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase of the formalin test. These results suggest that zaprinast is effective against both acute pain and the facilitated pain state at the spinal level. However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord.