Micro/nanomotors, as a breakthrough in the field of nanotechnology, have attracted attention for their unique autonomous motion characteristics and wide range of applications. Nanoscale micro-machines, ranging from tens of nanometers to tens of micrometers in size, can convert chemical energy from the environment or other forms of energy — such as light, sound, electricity, and magnetism — into mechanical energy for autonomous movement [[1], [2], [3]]. As research on micro/nanomotors deepens, they are becoming increasingly diverse. They are generally categorized based on their driving mechanisms: chemical-propelled MNMs [[4], [5], [6]], magnetic-propelled MNMs [7,8], light-propelled MNMs [[9], [10], [11], [12]], acoustic-propelled MNMs [[13], [14], [15]], and electric-propelled MNMs [16,17]. Compared with traditional technologies, the core advantages of micro/nanomotors lie in their small size, autonomous propulsive motion capability, targeted action site and functional diversity, which make them more flexible and maneuverable. In recent years, micro/nanomotors have shown great potential for application in biomedical [[18], [19], [20], [21]], agricultural production [22,23], environmental monitoring [[24], [25], [26], [27]] and other fields. For example, micro/nanomotors can actively traverse biological barriers in vivo to accomplish tasks [28], such as medicine delivery [29,30], gene editing [31], and cell therapy [32], it can also detect heavy metals and drug residues in the environment for overdose [[33], [34], [35], [36]].
Due to micro/nanomotors’ rapid movement ability, they are used in a wide range of biomedical applications, including medicine delivery [[37], [38], [39], [40]], bio-imaging [[41], [42], [43], [44]], disease diagnosis [[45], [46], [47], [48]] and microsurgery [[49], [50], [51], [52]], but they also have some limitations in practical applications. Currently, micro/nanomotors are easily recognized as foreign objects in the body, and the immune system will treat them as targets for removal, which leads to low biocompatibility and weak targeting, ultimately limit the efficacy of drugs [[53], [54], [55]]. Hence, the exploration of new drug delivery systems emerges as a crucial endeavor. Researchers have proposed new strategies to combine nanomotors with cells or cell extracts to improve the biocompatibility of the motors as well as barrier penetration [56]. Cell and cellular component based micro/nanomotors are specialized types of micro/nanomotors prepared by combining microorganisms, intact cells or specific extracts of cells with nanomaterials [57]. These motors not only have the ability to convert chemical energy from the surrounding environment, as well as other forms of energy such as light, sound, electricity, and magnetism, into energy to drive their own motion, but also have the advantage of being able to achieve more precise and efficient biomedical applications by virtue of their unique structure and performance, which opens up new paths in the development of the biomedical field.
Such motors, due to the combination of biological extracts, are usually well biocompatible and biodegradable, can reduce the body’s immune response, stabilize and function in the body, and effectively improve the safety and effectiveness of treatment [19,58]. There are various classifications of cell and cellular component based micro/nanomotors. According to the classification of cell types, cell micro/nanomotors mainly include four types: fungi [59], microalgae, bacteria [60], and mammalian cell types [[61], [62], [63]]. Fungal nanomotors usually utilize fungal cells or their extracts as carriers, which have good biocompatibility and low toxicity and are suitable for drug delivery. Bacterial nanomotors, on the other hand, take advantage of the natural chemotaxis and motility of bacteria, and are capable of actively targeting diseased sites, such as tumor tissues. Mammalian cell-based nanomotors, on the other hand, utilize the natural functions of mammalian cells (e.g., neutrophils, macrophages, etc.) to be able to cross biological barriers and deliver drugs precisely. Bionic motors, on the other hand, are made by modifying micro/nanomotors with components isolated from cells (e.g., cell membranes, mitochondria, etc.) [[64], [65], [66], [67]]. The advantage of cellular component-based motors is that they are relatively simple to prepare and do not require intact cells, thus offering broader prospects for clinical translation [[64], [65], [66], [67]].
Compared with traditional micro/nanomotors, the advantages of cell and cellular component based micro/nanomotors are mainly in the aspects of biocompatibility, functional diversity and environmental adaptability [68]. Due to the combination of the advantages of biomolecules and nanotechnology, they are usually well biocompatible, which means that they are less likely to trigger an immune response or rejection when entering an organism. This makes cell and cellular component based micro/nanomotors safer and more reliable for biomedical applications [69,70]. In addition, cell and cellular component based micro/nanomotors are more versatile. They can be loaded with drugs, cells, or other bioactive molecules and deliver them to the target location through autonomous motion, enabling precision medicine and targeted therapy [71]. At the same time, they can also sense the environmental changes of the lesions in the organism, such as pH, temperature, and adjust their own movement and the rate of drug release according to these changes [72]. Cell and cellular component based micro/nanomotors are also more adaptable to the environment, and they can work stably in complex biological environments and are less susceptible to external interferences, which makes bio-hybridized micro/nanomotors exhibit extensive potential applications within the realm of biosensing, disease diagnosis and therapy. These motors can mimic the cellular motions in nature or in the human body, and there are two kinds of motion mechanisms, one directly utilizes the motility of microorganisms or cells themselves to drive the motors, for example, the flagellum drive of bacteria and mammalian spermatozoa [73,74], the other is to generate propulsion through the motors by triggering a chemical reaction inside the organism or to drive the motors under the action of a physical field [75,76].
The practical applications of cell and cellular component based micro/nanomotors are mainly focused on the biomedical field, especially in active targeted drug delivery showing great potential. They are capable of overcoming various biological barriers in the body, such as immune clearance, blood barrier, blood-brain barrier, etc. In addition, micro/nanomotors have shown unique advantages in vivo imaging, enabling cross-scale in vivo imaging by fluorescence microscopy, MRI, and other techniques. For example, Li et al. investigated a multifunctional spiral microalgae that deposits bio-gold nanoparticles intracellularly and assembles magnetite nanoparticles on its surface in an ordered manner [77]. This biological hybridization microalgae can be used for gold-enhanced digital subtraction angiography imaging for real-time tracking of deep anatomical regions, while its photothermal effect shows potential for anticancer and antimicrobial therapies as well as optically controlled degradation.
This article briefly introduces the classification of micro/nanomotors, and also details the applications of different types of cell micro/nanomotors (e.g., fungi, bacteria, mammalian cells) and cellular component based micro/nanomotors (e.g., cell membranes, organelles, and enzymes) in the last three years in the areas of drug delivery, immunotherapy, gene editing, and tissue repair. Finally, the article summarizes the challenges of current research and future directions, emphasizing the need to improve the stability of micro/nanomotors, extend their circulation time in vivo, and precisely control their motions. In the future, research on micro/nanomotors will continue to address the challenges of prolonging the residence time of nanomotors in vivo, improving their stability and large-scale preparation to further promote their applications in biomedical fields.
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