Untethered Microrobots for Active Drug Delivery: From Rational Design to Clinical Settings

Abstract

Recent advances of untethered microrobots, which navigate the complex regions in vivo for therapeutics, have presented promising multiple applications on future healthcare. Microrobots used for active drug delivery system (DDS) have been demonstrated for advanced targeting distribution, improved delivery efficiency, and reduced systemic side effects. In this review, the therapeutic benefits of active DDS are presented compared to the traditional passive DDS, which illustrate the historical reasons for choosing active DDS. An integrated 5D radar chart analysis model containing the core capabilities of the active DDS is innovatively proposed. It would be a practical tool for measurement and mapping of the field of active delivery, followed by the evolutions and bottlenecks of each technical module. The comprehensive consideration of microrobots before clinical application is also discussed from the aspects of robot ethics, dosage, quality control and stability control in actual production. Gastrointestinal and blood administration, as two major clinical scenes of drug delivery, are discussed in detail as examples of the potential bedside applications of active DDS. Finally, combined with the reported analysis model, the current status and future outlook from the translation prospect to the clinical scenes of microrobots are provided.

Nanorobots with Hybrid Biomembranes for Simultaneous Degradation of Toxic Microorganism

“…A twofold RBC-PL film coating would provide nanorobots with diverse set of operational molecules, allowing them to perform a wide range of biological activities. As a result, these bioinspired nanorobots were projected to capture and eliminate RBC-targeted PFTs as well as PL-bound microorganisms, which create those PFTs [7]. To put this notion to the proof, we will use a recently advanced cell membrane-coating method to produce a stable and acoustical gold nanowire-(AuNW-) based nanorobot that will be utilized as a demonstration of an energy robot having possible biomedical uses.…”

Puffball‐Inspired Microrobotic Systems with Robust Payload, Strong Protection, and Targeted Locomotion for On‐Demand Drug Delivery

“…In turn, this limited loading capacity restricts treatment efficacy despite improved targeting compared to passive DDSs. [22] Due to the insufficient internal volume for drug loading, surface coating [11a,20,23] or grafting [13,[18][19]24] is a popular alternative drug-loading strategy for microrobots. However, these approaches often exhibit poor drug protection as, during the transport process, the surfacebound drugs may interact with existing inhibitors or the complex fluid environment, resulting in premature in vivo inactivation.…”

Biohybrid Magnetic Microrobots for Tumor Assassination and Active Tissue Regeneration

“…Micro-/nanorobotics have attracted significant interest for diverse biomedical applications, such as active drug delivery, regenerative medicine, biosensing, precise surgery, and detoxification. − Various actuation strategies for controlling micro-/nanorobots were reported, including biological hybrid, − chemical propelling, − and external field (e.g., electric, magnetic, light, and ultrasonic field). − Among them, magnetically controlled actuation has been widely used for its programmability, wireless feature, and penetrating capacity. − Great progress has also been made on the design, fabrication, imaging, and biodegradability of the microrobots, trying to put forward the comprehensive application of microrobots to bedside. − To fabricate the desired microrobots with specific functions, diverse fabrication strategies, including chemical synthesis and physical micromachining, were developed. − For instance, emulsion templating and microfluidics methods have been utilized for the fabrication of medical microrobot. , In order to rationally design and produce microrobots with diverse morphologies at microscale, precision printing technologies like 3D laser lithography and two-photon printing, were developed, and thus microrobots with a variety of morphologies were reported and utilized in biomedical scenes. − However, these fabrication methods were limited by the cost-effectiveness, complexity, and scalability.…”