Acoustically Driven Cell-Based Microrobots for Targeted Tumor Therapy

Abstract

Targeted drug delivery using microrobots manipulated by an external actuator has significant potential to be a practical approach for wireless delivery of therapeutic agents to the targeted tumor. This work aimed to develop a novel acoustic manipulation system and macrophage-based microrobots (Macbots) for a study in targeted tumor therapy. The Macbots containing superparamagnetic iron oxide nanoparticles (SPIONs) can serve as drug carriers. Under an acoustic field, a microrobot cluster of the Macbots is manipulated by following a predefined trajectory and can reach the target with a different contact angle. As a fundamental validation, we investigated an in vitro experiment for targeted tumor therapy. The microrobot cluster could be manipulated to any point in the 4 × 4 × 4 mm region of interest with a position error of less than 300 μm. Furthermore, the microrobot could rotate in the O-XY plane with an angle step of 45 degrees without limitation of total angle. Finally, we verified that the Macbots could penetrate a 3D tumor spheroid that mimics an in vivo solid tumor. The outcome of this study suggests that the Macbots manipulated by acoustic actuators have potential applications for targeted tumor therapy.

Ultrasonic Manipulation of Hydrodynamically Driven Microparticles in Vessel Bifurcation: Simulation, Optimization, Experimental Validation, and Potential for Targeted Drug Delivery

“…For the investigation, we employed COMSOL Multiphysics ® software (version 5.4, COMSOL Inc., Burlington, MA, USA) to simulate and analyze the following relevant acoustic phenomena: acoustic fields, acoustic radiation force, and interactions between particles and a fluid medium within a vessel bifurcation channel. Initially, a computational simulation was conducted to model an array of 30 ultrasonic transducers (UTs) operating at a resonance frequency of 1 MHz, along with a 3D manipulation control technique [ 46 ]. Subsequently, the resultant acoustic fields were integrated into our vessel’s geometric configuration using the particle tracing for fluid flow (fpt) module within the COMSOL software.…”

Cell‐Based Micro/Nano‐Robots for Biomedical Applications: A Review

“…[ 59 ] The propulsion mechanisms of micro/nano‐robots include self‐ and external field‐propelled types according to the energy source. The self‐propelled type generally refers to chemical actuation, [ 60 ] whereas the external field‐propelled type includes magnetic, [ 61 ] acoustic, [ 62 ] and optoelectronic actuation. [ 63,64 ] Herein, we introduce the principles, applications, and comparisons of these actuation types ( Table 1 ).…”

Applications and Future Prospects of Micro/Nanorobots Utilizing Diverse Biological Carriers

“…Various in vitro experiments demonstrated the effectiveness of this approach. Cao et al [ 35 ] considered the limitations of conventional manipulation modes and chose an acoustic manipulation system for macrophage-based MNRs containing magnetic nanoparticles. These motors can be pinpointed and rotated with high accuracy in a three-dimensional space.…”

“…Biohybrid micro-nano robots (BMNRs) combine artificial materials and biological entities, offering functions and advantages that only man-made motors lack [ 26 ]. Scientists have used bacteria [ 5 , 27 , 28 , 29 , 30 , 31 ], immune cells [ 32 , 33 , 34 , 35 , 36 ], and sperm [ 37 , 38 , 39 , 40 , 41 ] as common biological carriers, each having a certain degree of voluntary movement. Compared to previous physical models, most biohybrid MNRs integrate phagocytic ability and cell-specific characteristics, enhancing drug net charge and therapeutic effects.…”