Manipulating the Crosstalk between Cancer and Immunosuppressive Cells with Phototherapeutic Gold-Nanohut for Reprogramming Tumor Microenvironment.

Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.

A Human-Scale Clinically Ready Electromagnetic Navigation System for Magnetically Responsive Biomaterials and Medical Devices.

Magnetic navigation systems are used to precisely manipulate magnetically responsive materials enabling the realization of new minimally invasive procedures using magnetic medical devices. Their widespread applicability has been constrained by high infrastructure demands and costs. The study reports on a portable electromagnetic navigation system, the Navion, which is capable of generating a large magnetic field over a large workspace. The system is easy to install in hospital operating rooms and transportable through health care facilities, aiding in the widespread adoption of magnetically responsive medical devices. First, the design and implementation approach for the system are introduced and its performance is characterized. Next, in vitro navigation of different microrobot structures is demonstrated using magnetic field gradients and rotating magnetic fields. Spherical permanent magnets, electroplated cylindrical microrobots, microparticle swarms, and magnetic composite bacteria-inspired helical structures are investigated. The navigation of magnetic catheters is also demonstrated in two challenging endovascular tasks: 1) an angiography procedure and 2) deep navigation within the circle of Willis. Catheter navigation is demonstrated in a porcine model in vivo to perform an angiography under magnetic guidance.

Case Report: Remote magnetic navigation and accessory pathways ablation in a single ventricle young adult with complex corrective surgeries.

Supraventricular arrhythmias have become an increasingly significant contributor to the risk of mortality and morbidity in adults with complex congenital heart disease (CHD), especially in light of recent advances in palliative corrective surgeries. Because of their unique characteristics, they demand specific treatment approaches. While pharmaco-logical interventions are an option, they have limited effectiveness and may lead to side effects. Although performing radiofrequency ablation (RFA) can be exceptionally challenging in patients with complex CHD, due to particular vascular access and also modified anatomy, it has paved the way to enhance comprehension of the underlying mechanisms of supraventricular arrhythmias. This, in turn, enables the provision of improved therapies and, ultimately, an enhancement in the quality of life and symptom management for these patients. The purpose of this case report is to highlight the benefits of utilizing advanced technologies such as three-dimensional electro-anatomical mapping systems, remote magnetic navigation, and highly flexible mapping and ablation catheters during RFA in a young adult with complex congenital heart disease. Although he lacked venous connections to the right atrium (RA) due to multiple corrective surgeries we, remarkably, were capable to advance a decapolar deflectable diagnostic catheter inside the Fontan tunnel and from there to record and stimulate the RA. Successful ablation of two accessory pathways was achieved with no arrhythmia recurrence during follow-up.

Autonomous Magnetic Navigation in Endoscopic Image Mosaics.

Endoscopes navigate within the human body to observe anatomical structures with minimal invasiveness. A major shortcoming of their use is their narrow field-of-view during navigation in large, hollow anatomical regions. Mosaics of endoscopic images can provide surgeons with a map of the tool's environment. This would facilitate procedures, improve their efficiency, and potentially generate better patient outcomes. The emergence of magnetically steered endoscopes opens the way to safer procedures and creates an opportunity to provide robotic assistance both in the generation of the mosaic map and in navigation within this map. This paper proposes methods to autonomously navigate magnetic endoscopes to 1) generate endoscopic image mosaics and 2) use these mosaics as user interfaces to navigate throughout the explored area. These are the first strategies, which allow autonomous magnetic navigation in large, hollow organs during minimally invasive surgeries. The feasibility of these methods is demonstrated experimentally both in vitro and ex vivo in the context of the treatment of twin-to-twin transfusion syndrome. This minimally invasive procedure is performed in utero and necessitates coagulating shared vessels of twin fetuses on the placenta. A mosaic of the vasculature in combination with autonomous navigation has the potential to significantly facilitate this challenging surgery.

Tetherless and Batteryless Soft Navigators and Grippers.

Remotely controllable soft actuators have promising potential applications in many fields including soft robotics, exploration, and invasion medical treatment. Shape memory polymers could store and release energy, resulting in shape deformation, and have been regarded as promising candidates to fabricate untethered soft robots. Herein, an untethered and battery-free soft navigator and gripper based on a shape memory hydrogel is presented. The shape memory hydrogel is obtained through hydrogen bonding between gelatin and tannic acid, and the hydrogel displays excellent shape memory properties on the basis of hydrogen bonding and the coil-triple helix transition of gelatin. Moreover, Fe3O4 nanoparticles are introduced to endow the hydrogel magnetic responsiveness and photothermal conversion capacity. Finally, the shape memory hydrogel in a stretched state is assembled with an inert hydrogel to achieve a bilayer hydrogel actuator, which could produce complex shape transformation due to the shape recovery of the shape memory layer induced by heat or light. Taking advantage of the magnetically control and light-responsive shape deformation, remotely controllable soft grippers that could navigate through tortuous paths and grasp objects from a hard-to-reach place have been accomplished. This approach will inspire the design and fabrication of novel shape memory hydrogels as remotely controllable soft robots.

Fast-Response Variable-Stiffness Magnetic Catheters for Minimally Invasive Surgery.

In minimally invasive surgery, such as cardiac ablation, magnetically steered catheters made of variable-stiffness materials can enable higher dexterity and higher force application to human tissue. However, the long transition time between soft and rigid states leads to a significant increase in procedure duration. Here, a fast-response, multisegmented catheter is described for minimally invasive surgery made of variable-stiffness thread (FRVST) that encapsulates a helical cooling channel. The rapid stiffness change in the FRVST, composed of a nontoxic shape memory polymer, is achieved by an active cooling system that pumps water through the helical channel. The FRVST displays a 66 times stiffness change and a 26 times transition enhancement compare with the noncooled version. The catheter allows for selective bending of each segment up to 127° in air and up to 76° in water under an 80 mT external magnetic field. The inner working channel can be used for cooling an ablation tip during a procedure and for information exchange via the deployment of wires or surgical tools.

Magnetically navigated microbubbles coated with albumin/polyarginine and superparamagnetic iron oxide nanoparticles.

While microbubbles (MB) are routinely used for ultrasound (US) imaging, magnetic MB are increasingly explored as they can be guided to specific sites of interest by applied magnetic field gradient. This requires the MB shell composition tuning to prolong MB stability and provide functionalization capabilities with magnetic nanoparticles. Hence, we developed air-filled MB stabilized by a protein-polymer complex of bovine serum albumin (BSA) and poly-L-arginine (pArg) of different molecular weights, showing that pArg of moderate molecular weight distribution (15-70 kDa) enabled MB with greater stability and acoustic response while preserving MB narrow diameters and the relative viability of THP-1 cells after 48 h of incubation. After MB functionalization with superparamagnetic iron oxide nanoparticles (SPION), magnetic moment values provided by single MB confirmed the sufficient SPION deposition onto BSA + pArg MB shells. During MB magnetic navigation in a blood vessel mimicking phantom with magnetic tweezers and in a Petri dish with adherent mouse renal carcinoma cell line, we demonstrated the effectiveness of magnetic MB localization in the desired area by magnetic field gradient. Magnetic MB co-localization with cells was further exploited for effective doxorubicin delivery with drug-loaded MB. Taken together, these findings open new avenues in control over albumin MB properties and magnetic navigation of SPION-loaded MB, which can envisage their applications in diagnostic and therapeutic needs.

Contact force sensing manual catheter versus remote magnetic navigation ablation of atrial fibrillation: a single-center comparison.

BACKGROUND: Data comparing remote magnetic catheter navigation (RMN) with manual catheter navigation in combination with contact force sensing (MCN-CF) ablation of atrial fibrillation (AF) is lacking. The primary aim of the present retrospective comparative study was to compare the outcome of RMN versus (vs.) MCN-CF ablation of AF with regards to AF recurrence. Secondary aim was to analyze periprocedural risk, ablation characteristics and repeat procedures. METHODS: We retrospectively analyzed 452 patients undergoing a total of 605 ablations of AF: 180 patients were ablated using RMN, 272 using MCN-CF. RESULTS: Except body mass index there was no significant difference between groups at baseline. After a mean 1.6 ± 1.6 years of follow-up and 1.3 ± 0.4 procedures, 81% of the patients in the MCN-CF group remained free of AF recurrence compared to 53% in the RMN group (P < 0.001). After analysis of 153 repeat ablations (83 MCN-RF vs. 70 RMN; P = 0.18), there was a significantly higher reconnection rate of pulmonary veins after RMN ablation (P < 0.001). In multivariable Cox-regression analysis, RMN ablation (P < 0.001) and left atrial diameter (P = 0.013) was an independent risk factor for AF recurrence. Procedure time, radiofrequency application time and total fluoroscopy time and fluoroscopy dose were higher in the RMN group without difference in total number of ablation points. Complication rates did not differ significantly between groups (P = 0.722). CONCLUSIONS: In our retrospective comparative study, the AF recurrence rate and pulmonary vein reconnection rate is significantly lower with more favorable procedural characteristics and similar complication rate utilizing MCN-CF compared to RMN.

Magnetoactive Millirobots with Ternary Phase Transition.

Magnetoactive soft millirobots have made significant advances in programmable deformation, multimodal locomotion, and untethered manipulation in unreachable regions. However, the inherent limitations are manifested in the solid-phase millirobot as limited deformability and in the liquid-phase millirobot as low stiffness. Herein, we propose a ternary-state magnetoactive millirobot based on a phase transitional polymer embedded with magnetic nanoparticles. The millirobot can reversibly transit among the liquid, solid, and viscous-fluid phases through heating and cooling. The liquid-phase millirobot has elastic deformation and mobility for unimpeded navigation in a constrained space. The viscous-fluid phase millirobot shows irreversible deformation and large ductility. The solid-phase millirobot shows good shape stability and controllable locomotion. Moreover, the ternary-state magnetoactive millirobot can achieve prominent capabilities including stiffness change and shape reconfiguration through phase transition. The millirobot can perform potential functions of navigation in complex terrain, three-dimensional circuit connection, and simulated treatment in a stomach model. This magnetoactive millirobot may find new applications in flexible electronics and biomedicine.

On-Command Disassembly of Microrobotic Superstructures for Transport and Delivery of Magnetic Micromachines.

Magnetic microrobots have been developed for navigating microscale environments by means of remote magnetic fields. However, limited propulsion speeds at small scales remain an issue in the maneuverability of these devices as magnetic force and torque are proportional to their magnetic volume. Here, a microrobotic superstructure is proposed, which, as analogous to a supramolecular system, consists of two or more microrobotic units that are interconnected and organized through a physical (transient) component (a polymeric frame or a thread). The superstructures consist of microfabricated magnetic helical micromachines interlocked by a magnetic gelatin nanocomposite containing iron oxide nanoparticles (IONPs). While the microhelices enable the motion of the superstructure, the IONPs serve as heating transducers for dissolving the gelatin chassis via magnetic hyperthermia. In a practical demonstration, the superstructure's motion with a gradient magnetic field in a large channel, the disassembly of the superstructure and release of the helical micromachines by a high-frequency alternating magnetic field, and the corkscrew locomotion of the released helices through a small channel via a rotating magnetic field, is showcased. This adaptable microrobotic superstructure reacts to different magnetic inputs, which can be used to perform complex delivery procedures within intricate regions of the human body.

Robotic magnetic navigation-guided catheter ablation establishes highly effective pulmonary vein isolation in patients with paroxysmal atrial fibrillation when compared to conventional ablation techniques.

INTRODUCTION: Pulmonary vein isolation (PVI) is a pivotal part of ablative therapy for atrial fibrillation (AF). Currently, there are multiple techniques available to realize PVI, including: manual-guided cryoballoon (MAN-CB), manual-guided radiofrequency (MAN-RF), and robotic magnetic navigation-guided radiofrequency ablation (RMN-RF). There is a lack of large prospective trials comparing contemporary RMN-RF with the more conventional ablation techniques. This study prospectively compared three catheter ablation techniques as treatment of paroxysmal AF. METHODS: This multicenter, prospective study included patients with paroxysmal AF who underwent their first ablation procedure. Procedural parameters (including procedural efficiency), complication rates, and freedom of AF during 12-month follow-up, were compared between three study groups which were defined by the utilized ablation technique. RESULTS: A total of 221 patients were included in this study. Total procedure time was significantly shorter in MAN-CB (78 ± 21 min) compared to MAN-RF (115 ± 41 min; p < .001) and compared to RMN-RF (129 ± 32 min; p < .001), whereas it was comparable between the two radiofrequency (RF) groups (p = .062). A 3% complication rate was observed, which was comparable between all groups. At 12-month follow-up, AF recurrence was observed in 40 patients (19%) and was significantly lower in the robotic group (MAN-CB 19 [24%], MAN-RF 16 [23%], RMN-RF 5 [8%] AF recurrences, p = .045) (multivariate hazard ratio of RMN-RF on AF recurrence 0.32, 95% confidence interval: 0.12-0.87, p = .026). CONCLUSION: RMN-guided PVI results in high freedom of AF in patients with paroxysmal AF, when compared to cryoablation and manual RF ablation. Cryoablation remains the most time-efficient ablation technique, whereas RMN nowadays has comparable efficiency with manual RF ablation.

Different electrophysiological characteristics of cavo-tricuspid isthmus dependent atrial flutter guided by robotic magnetic navigation in patients with and without prior cardiac surgery.

BACKGROUD: Cavo- tricuspid isthmus dependent atrial flutter (CTI- AFL) is a common atrial arrhythmia in patients with prior cardiac surgery (postsurgical AFL) and without prior cardiac surgery (nonsurgical AFL). However, there is only limited data regarding the eletrophysiological differences between the CTI- AFL in the postsurgical patients and the nonsurgical patients. HYPOTHESIS: We aimed to investigate the differences in clinical and electrophysiological characteristics between the postsurgical group and nonsurgical group and to evaluate the acute and long-term outcomes after ablation guided by robotic magnetic navigation (RMN) in both the groups. Methods Fourty-two consecutive patients with nonsurgical AFL and 21 with postsurgical AFL were retrospectively analyzed in our center. Electrocardiographic (ECG) analysis and three-dimensional electrophysiological study were performed in all the patients. RESULTS: The results revealed that only 55.6% of postsurgical patients with proven counterclockwise (CCW) AFL presented with a typical ECG suggesting this mechanism. In contrast, 86.1% of nonsurgical patients demonstrated a typical ECG pattern for CCW AFL. In addition, we employed a reverse "U-curve" to facilitate radiofrequency delivery when ablating near the inferior vena cava ostium in the present study. Compared with the nonsurgical group, electroanatomical mapping showed the mean AFL cycle length was significantly longer (253.3 ± 40.4 vs. 234.1 ± 24.2 ms, p = 0.03) and the right atrium volume was larger (114.8 ± 26.0 vs. 97.5 ± 19.1 mL, p = 0.004) in the postsurgical group. Additionally, the procedural time (75.9 ± 21.3 vs. 61.6 ± 26.6 minutes, p = 0.03) and ablation time (53.0 ± 21.4 vs. 36.7 ± 25.6 minutes, p = 0.02) are much longer in the postsurgical group. However, the navigation index in the postsurgical group was significantly smaller (0.35 ± 0.08 vs. 0.43 ± 0.13, p = 0.01). Moreover, the acute and long-term success rates were comparable between the two groups. CONCLUSIONS: Catheter ablation of CTI-AFL with and without prior cardiac surgery guided by RMN are associated with high acute and long-term success rates, despite the procedural and ablation times are much longer in the postsurgical patients. However, ECG characteristics of the tachycardia may be misleading as they are more often atypical in patients after cardiac surgery.

Analysis of influence of surgical instruments on accuracy of magnetic navigation system for craniofacial surgery robots.

IntroductionIn craniofacial surgery, magnetic navigation systems can effectively extend the doctor's limited visual range, improve their surgical precision, shorten the operation time, and reduce the incidence of surgical complications. Owing to the ease of magnetic navigation, the accuracy of the magnetic navigation system is affected by various equipment in the operating room. Therefore, its large-scale application is lacking because the navigation accuracy requirement can be extremely high during craniofacial surgery. Therefore, the accuracy of magnetic navigation systems is crucial. Various surgical instruments have been evaluated to effectively reduce the interference of magnetic navigation systems with surgical instruments. In craniofacial surgery, magnetic navigation systems can effectively extend the doctor's limited visual range, improve their surgical precision, shorten the operation time, and reduce the incidence of surgical complications. Owing to the ease of magnetic navigation, the accuracy of the magnetic navigation system is affected by various equipment in the operating room. Therefore, its large-scale application is lacking because the navigation accuracy requirement can be extremely high during craniofacial surgery. Therefore, the accuracy of magnetic navigation systems is crucial. Various surgical instruments have been evaluated to effectively reduce the interference of magnetic navigation systems with surgical instruments. In the surgical environment, the use of surgical instruments during mandibular surgery was simulated by selecting several conventional surgical instruments to record errors in the magnetic navigation system. The fluctuation values of the magnetic navigation errors were subsequently estimated and changes in its accuracy measured. MATLAB was used to calculate and analyze the fluctuations of the magnetic navigation errors. As results, the high-frequency electrosurgical system caused the greatest interference with the magnetic navigation system during surgery while powered on, with a maximum fluctuation error value of 1.8120 mm, and the maximum fluctuation error values of the stitch scissors, teeth forceps, and a needle holder were 1.3662, 1.3781, and 0.3912 mm, respectively. The closer the instrument is to the magnetic field generator or navigation target, the greater its impact. In conclusion, stitch scissors, teeth forceps, a needle holder, and the high-frequency electrosurgical system all affect magnetic navigation system accuracy. Therefore, it is necessary to avoid magnetic navigation system use and surgical instrument disturbances during surgery or select surgical instruments that do not interfere with the system. Surgical instruments must be evaluated for electromagnetic interference before they can be used in surgery with a magnetic navigation system.

Robotic magnetic navigation-guided pulmonary vein isolation in an atrial fibrillation patient with dextrocardia situs inversus: techniques and potential advantages.

BACKGROUND: Dextrocardia with situs inversus (DSI) is a very rare congenital anomaly. Catheter manipulation and ablation of atrial fibrillation (AF) in patients with this anatomical variant is challenging for the operators. This case report presents a safe and effective AF ablation guided by the robotic magnetic navigation (RMN) system in combination with intracardiac echocardiograhy (ICE) in a patient with DSI. CASE PRESENTATION: A 64-year-old male with DSI was referred for catheter ablation of symptomatic, drug-refractory paroxysmal AF. One transseptal access was achieved via the left femoral vein under the guidance of ICE. The three-dimensional reconstruction of the left atrium and the pulmonary veins (PVs) were performed by the magnetic catheter using the CARTO and the RMN system. Then, the electroanatomic map and pre-acquired CT images were merged. Finally, bilateral circumferential ablation lines were delivered around the ipsilateral PV ostia to achieve complete PV isolation (PVI). CONCLUSIONS: This case demonstrates that AF catheter ablation under the guidance of the RMN system using ICE is feasible and safe in a patient with DSI. Moreover, the combination of these technologies broadly facilitates treatment of patients with complex anatomy, while reducing the risk of complications.

The performance of dipole charge density mapping integrated with robotic magnetic navigation in the treatment of atrial tachycardias.

BACKGROUND: Catheter ablation (CA) has become a well-established first-line therapy for a broad spectrum of arrhythmias, including atrial tachycardias (ATs). In this study we aimed to assess the performance of the integrated novel high-resolution new generation noncontact mapping system (AcQMap) with robotic magnetic navigation (RMN) system in CA procedures for patients with ATs including comparing patient subgroups based on the utilized mapping modality, arrhythmia mechanism, localization and type of procedure. METHODS: All patients undergoing CA for AT using the AcQMap-RMN system were included. Procedural safety and efficacy were characterized by intra- and post-procedural complications. Acute procedural success and the long-term outcome were assessed in the overall group and in the subgroups. RESULTS: A total number of 70 patients were referred for CA with atrial arrhythmias including 67 AT/AFL (mean age 57.1 ± 14.4 years), and 3 additional patients with inappropriate sinus tachycardia. Thirty-eight patients had de novo AT, 24 had post-PVI AT including 2 patients with perinodal AT, and 5 had post-MAZE AT. Two patients (2.9%) suffered post-procedural complications including 1 patient with groin hematoma and 1 patient with a transient ischemic attack. Acute success was achieved in 63/67 (94.0%) procedures. Thirteen patients (19.4%) had documented recurrence at the end of the 12-months follow-up period. The performance of AcQMap was equally good in focal vs. reentry mechanisms (p = 0.61, acute success), in the left and right atrium (p = 0.21). CONCLUSIONS: AcQMap-RMN integration might improve success rates in CA of ATs with low number of complications.

Actuation technologies for magnetically guided catheters.

Due to their wide range of clinical application possibilities, magnetic actuation technologies have grabbed the attention of researchers worldwide. The design, execution, and analysis of magnetic catheter systems have advanced significantly during the last decade. The review focuses on magnetic actuation for catheter steering and control of the device, which will be explored in detail in the following sections. There is a discussion of future work and the challenges of the review systems, and the conclusions are finally addressed.

Radiofrequency ablation of premature ventricular contractions guided by robotic magnetic navigation combined with pattern matching filter.

BACKGROUND: This study's intent is to evaluate the usefulness of pattern matching filter (PMF) function combined with robotic magnetic navigation (RMN) in guiding the ablation of premature ventricular contractions (PVCs). HYPOTHESIS: Assume that PMF can improve the outcomes of PVCs ablation using RMN. METHODS: A retrospective analysis was completed consisting of 118 consecutive patients with PVCs who underwent radiofrequency ablation guided by RMN. According to the application of PMF, patients were divided into two groups: 20 patients underwent ablation without PMF (group A), and another 98 patients received ablation incorporating PMF (group B). RESULTS: Compared with group A, the procedure time (135.0 ± 28.3 min vs. 106.3 ± 37.9 min, p = 0.02) in group B was significantly decreased, while the X-ray exposure time (6.0 ± 2.6 min vs. 6.5 ± 3.6 min, p = 0.705) and dose (3.2 ± 2.4 gycm2 vs. 3.9 ± 2.7 gycm2 ，p = 0.208) had no significant difference. Group B had a more than twofold number of points acquired (66.9 ± 23.0 vs. 143.9 ± 68.3, p < 0.001) and required a shorter radiofrequency ablation time (13.2 ± 3.5 min vs. 8.1 ± 2.9 min, p < 0.001). There were no serious complications in either group. The acute success rate was similar [90.0% (18/20) vs. 87.8% (86/98), p = 1.000] in two groups, and the success rate was also similar in the long-term follow-up [83.3% (15/18) vs. 87.2% (75/86), p = 0.776]. CONCLUSIONS: The ablation of PVCs guided by RMN is safe and effective. Combined with the functional capability of PMF, both procedure time and radiofrequency ablation time were significantly decreased.