Towards multifunctional robotic pills.

Robotic pills leverage the advantages of oral pharmaceutical formulations-in particular, convenient encapsulation, high loading capacity, ease of manufacturing and high patient compliance-as well as the multifunctionality, increasing miniaturization and sophistication of microrobotic systems. In this Perspective, we provide an overview of major innovations in the development of robotic pills-specifically, oral pills embedded with robotic capabilities based on microneedles, microinjectors, microstirrers or microrockets-summarize current progress and applicational gaps of the technology, and discuss its prospects. We argue that the integration of multiple microrobotic functions within oral delivery systems alongside accurate control of the release characteristics of their payload provides a basis for realizing sophisticated multifunctional robotic pills that operate as closed-loop systems.

A Microstirring Oral Pill for Improving the Glucose-Lowering Effect of Metformin.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to persistent insulin resistance, resulting in elevated blood glucose levels. Metformin is the most prescribed oral drug for lowering high blood glucose levels in T2DM patients. However, it is poorly absorbed and has low bioavailability. Here, we introduce magnesium-based microstirrers to a metformin-containing pill matrix to enhance the glucose-lowering effect of metformin. The resulting microstirring pill possesses a built-in mixing capability by creating local fluid transport upon interacting with biological fluid to enable fast pill disintegration and drug release along with accelerated metformin delivery. In vivo glucose tolerance testing using a murine model demonstrates that the metformin microstirring pill significantly improves therapeutic efficacy, lowering blood glucose levels after a meal more rapidly compared to a regular metformin pill without active stirring. As a result, the microstirrers allow for dose sparing, providing effective therapeutic efficacy at a lower drug dosage than passive metformin pills. These encouraging results highlight the versatility of this simple yet elegant microstirring pill technology, which enhances drug absorption after gastrointestinal delivery to improve therapeutic efficacy.

Biomembrane-Functionalized Micromotors: Biocompatible Active Devices for Diverse Biomedical Applications.

There has been considerable interest in developing synthetic micromotors with biofunctional, versatile, and adaptive capabilities for biomedical applications. In this perspective, cell membrane-functionalized micromotors emerge as an attractive platform. This new class of micromotors demonstrates enhanced propulsion and compelling performance in complex biological environments, making them suitable for various in vivo applications, including drug delivery, detoxification, immune modulation, and phototherapy. This article reviews various proof-of-concept studies based on different micromotor designs and cell membrane coatings in these areas. The review focuses on the motor structure and performance relationship and highlights how cell membrane functionalization overcomes the obstacles faced by traditional synthetic micromotors while imparting them with unique capabilities. Overall, the cell membrane-functionalized micromotors are expected to advance micromotor research and facilitate its translation towards practical uses.

ACE2 Receptor-Modified Algae-Based Microrobot for Removal of SARS-CoV-2 in Wastewater.

The coronavirus SARS-CoV-2 can survive in wastewater for several days with a potential risk of waterborne human transmission, hence posing challenges in containing the virus and reducing its spread. Herein, we report on an active biohybrid microrobot system that offers highly efficient capture and removal of target virus from various aquatic media. The algae-based microrobot is fabricated by using click chemistry to functionalize microalgae with angiotensin-converting enzyme 2 (ACE2) receptor against the SARS-CoV-2 spike protein. The resulting ACE2-algae-robot displays fast (>100 µm/s) and long-lasting (>24 h) self-propulsion in diverse aquatic media including drinking water and river water, obviating the need for external fuels. Such movement of the ACE2-algae-robot offers effective "on-the-fly" removal of SARS-CoV-2 spike proteins and SARS-CoV-2 pseudovirus. Specifically, the active biohybrid microrobot results in 95% removal of viral spike protein and 89% removal of pseudovirus, significantly exceeding the control groups such as static ACE2-algae and bare algae. These results suggest considerable promise of biologically functionalized algae toward the removal of viruses and other environmental threats from wastewater.