Introduction: Recent advancements in micro/nanorobots for biomedical applications have gained significant momentum due to their potential to revolutionize targeted therapies. These cell-sized machines offer unmatched precision, enabling them to navigate through hard-to-reach biological environments. Over the past decade, there have been considerable advancements in the development of functional and biocompatible micro/nanorobots. Innovations have enhanced navigation control, cue responsiveness, and drug payload efficiency. However, challenges remain, particularly regarding minimizing toxicity and optimizing movement through complex environments.
Methods: This review focuses on preclinical studies conducted using animal models to assess the real-world applications of micro/nanorobots. We performed a comprehensive literature search using the PubMed database, focusing on original research articles published between 2014 and 2024. Keywords such as “microrobots,” “nanorobots,” “targeted therapy,” and “in-vivo” were employed to identify relevant studies.
Results: Significant advancements have been made in the design, administration, actuation, and monitoring of micro/nanorobots across various organs and diseases, particularly in cancer models. These devices have evolved to perform increasingly complex tasks beyond drug delivery. Efforts to utilize biocompatible materials in micro/nanorobots, in compliance with ISO10993-1 standards, aim to develop large-scale fabrication techniques. Notable studies demonstrated successful in-vivo applications of micro/nanorobots, including targeted drug delivery of cisplatin for colorectal cancer, minimally invasive intraocular surgery and safe extraction of nanorobots, tissue sample collection of bile duct, Mesenchymal stem cell delivery to liver cancer tumor site and ROS scavenging in rheumatoid arthritis among others. Furthermore, modern imaging approaches were proposed to monitor these devices in real-time, including the use of chemical contrast agents (barium- and iodine-based), photoacoustic imaging (PAI), photoacoustic computed tomography (PACT), and ultrasound, among others.
Conclusion: Advancements in micro/nanorobots can be classified into three main areas: actuation methods, design & fabrication, and imaging modalities. Together, these advancements form novel platforms that are transforming not only drug delivery but also non-invasive microsurgeries and sample collection techniques. Unlike conventional targeted drug delivery, micro/nanorobots can be programmed to be autonomous (chemical and biohybrid actuation methods) or semi-autonomous (acoustic, magnetic, and light-based actuation). These propulsion methods enable deep tissue penetration, previously inaccessible. Among these, magnetic micro/nanorobots are currently the most prevalent due to their ease of navigation and imaging, alongside the absence of toxic byproducts from chemical methods.
Despite their advantages, each actuation method presents unique pros and cons depending on the specific disease and organ targeted. Regardless of the approach, the use of non-toxic and biocompatible materials is essential, as clinical trials are on the horizon. In addition to precise targeting through receptor-ligand interactions, nanorobots benefit from features such as special coatings and integrated sensors. The integration of drug delivery, imaging, and biosensing capabilities further enhances their functionality. Combined imaging approaches, such as PAI with high-frequency ultrasound or positron emission tomography (PET) with computed tomography (CT), were shown to improve tracking and monitoring, distinguishing between endogenous signals from motile microrobots. Despite the substantial progress, many challenges remain, such as optimizing biocompatibility, navigation in complex biological environments, and scalability for clinical applications. Addressing these hurdles is critical for translating micro/nanorobots from preclinical success to widespread medical use, potentially redefining the future of minimally invasive therapies and precision medicine.