Biorobotic Drug Delivery for Biomedical Applications

Abstract

Despite extensive efforts, current drug-delivery systems face biological barriers and difficulties in bench-to-clinical use. Biomedical robotic systems have emerged as a new strategy for drug delivery because of their innovative diminutive engines. These motors enable the biorobots to move independently rather than relying on body fluids. The main components of biorobots are engines controlled by external stimuli, chemical reactions, and biological responses. Many biorobot designs are inspired by blood cells or microorganisms that possess innate swimming abilities and can incorporate living materials into their structures. This review explores the mechanisms of biorobot locomotion, achievements in robotic drug delivery, obstacles, and the perspectives of translational research.

Keywords: biological engine; biorobot; drug-delivery systems; locomotion.

Figure 1

Drug-delivery systems based on biorobots. (A) Biorobots are designed with various shapes and engines (Red: biorobot; blue: illustrative motion path of biorobot). (B) Diversity of biorobots operating within various physiological environments: vitreous matrix, tumor tisssue, cartilage tissue, blood-brain barrier, gastric lumen, and intestinal lumen (Red circle: biorobot; green-glared red circle: biororobot for in vivo imaging).

Figure 2

Examples of cargo drugs used in robotic delivery systems. Various payload types, including small molecules (A), siRNAs (B), and proteins (C) are loaded in biorobotic platforms to enhance delivery efficacy. Reprinted with permission from [30,34,39], respectively.

Figure 3

Design of biorobotic platforms for protein and cell delivery. (A). An oral vaccine based on an autonomous microrobot for delivery of Staphylococcal α-toxin antigen [40]. (B) Construction of a microrobot using chitosan-PLGA scaffold for delivery of mesenchymal stem cells into damaged cartilage with assistance of an electromagnetic articulography system (EMA). PLGA-based microrobot was prepared by absorption of feromoxytol-chitosan microcluters (i) following the loading of mesenchymal stem cells (ii). (iii)The microrobot was injected into the knee joint, and its movement was controlled by an EMA system [46]. Reprinted with permission from [40,46].

Figure 4

Representative robotic devices allowing active delivery of therapeutic drugs or cells to the targeted sites in various disease treatments. (A) NO generation by L-arginine in the tumor microenvironment propels the nanoparticles and induces anticancer effects. Reprinted with permission from [70]. (B) Navigation of micro-propeller by photoacoustic computed tomography for targeted delivery in gastrointestinal diseases (a). A set up of photo ascoutic computed tomography for gastric intestinal imaging (b). Micro-propeller is protected in gastric environment by enteric coating (c) and activated in intestine lumen by NIR irradiation (d). Exposure of Mg layer induced gas generation driving biorobot’s motion (e). Reprinted with permission from [71]. (C) The helical nanopropeller is able to penetrate the high-viscosity matrix, which is crucial for drug delivery in vitreous environment. (a) Illustrative motion of helical propeller and (b) helical shape was imaged by transmission electron microscopy. Reprinted with permission from [72].