Cancer Cell Membrane Camouflaged Semi‐Yolk@Spiky‐Shell Nanomotor for Enhanced Cell Adhesion and Synergistic Therapy

Cell adhesion of nanosystems is significant for efficient cellular uptake and drug delivery in cancer therapy. Herein, a near‐infrared (NIR) light‐driven biomimetic nanomotor is reported to achieve the improved cell adhesion and cellular uptake for synergistic photothermal and chemotherapy of breast cancer. The nanomotor is composed of carbon@silica (C@SiO₂) with semi‐yolk@spiky‐shell structure, loaded with the anticancer drug doxorubicin (DOX) and camouflaged with MCF‐7 breast cancer cell membrane (i.e., mC@SiO₂@DOX). Such biomimetic mC@SiO₂@DOX nanomotors display efficient self‐thermophoretic propulsion due to a thermal gradient generated by asymmetrically spatial distribution. Moreover, the MCF‐7 cancer cell membrane coating can remarkably reduce the bioadhesion of nanomotors in biological medium and exhibit highly specific self‐recognition of the source cell line. The combination of effective propulsion and homologous targeting dramatically improves cell adhesion and the resultant cellular uptake efficiency in vitro from 26.2% to 67.5%. Therefore, the biomimetic mC@SiO₂@DOX displays excellent synergistic photothermal and chemotherapy with over 91% MCF‐7 cell growth inhibition rate. Such smart design of the fuel‐free, NIR light‐powered biomimetic nanomotor may pave the way for the application of self‐propelled nanomotors in biomedicine.     

Fuel‐Free Synthetic Micro‐/Nanomachines

Inspired by the swimming of natural microorganisms, synthetic micro‐/nanomachines, which convert energy into movement, are able to mimic the function of these amazing natural systems and help humanity by completing environmental and biological tasks. While offering autonomous propulsion, conventional micro‐/nanomachines usually rely on the decomposition of external chemical fuels (e.g., H₂O₂), which greatly hinders their applications in biologically relevant media. Recent developments have resulted in various micro‐/nanomotors that can be powered by biocompatible fuels. Fuel‐free synthetic micro‐/nanomotors, which can move without external chemical fuels, represent another attractive solution for practical applications owing to their biocompatibility and sustainability. Here, recent developments on fuel‐free micro‐/nanomotors (powered by various external stimuli such as light, magnetic, electric, or ultrasonic fields) are summarized, ranging from fabrication to propulsion mechanisms. The applications of these fuel‐free micro‐/nanomotors are also discussed, including nanopatterning, targeted drug/gene delivery, cell manipulation, and precision nanosurgery. With continuous innovation, future autonomous, intelligent and multifunctional fuel‐free micro‐/nanomachines are expected to have a profound impact upon diverse biomedical applications, providing unlimited opportunities beyond one's imagination.     

Self‐Propelled Micro/Nanomotors for On‐Demand Biomedical Cargo Transportation

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on‐demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self‐propelled MNMs for on‐demand biomedical cargo transportation, including their self‐propulsion mechanisms, guidance strategies, as well as proof‐of‐concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.     

Smartdust 3D‐Printed Graphene‐Based Al/Ga Robots for Photocatalytic Degradation of Explosives

Milli/micro/nanorobots are considered smart devices able to convert energy taken from different sources into mechanical movement and accomplish the appointed tasks. Future advances and realization of these tiny devices are mostly limited by the narrow window of material choices, the fuel requirement, multistep surface functionalization, rational structural design, and propulsion ability in complex environments. All these aspects call for intensive improvements that may speed up the real application of such miniaturized robots. 3D‐printed graphene‐based smartdust robots provided with a magnetic response and filled with aluminum/gallium molten alloy (Al/Ga) for autonomous motion are presented. These robots can swim by reacting with the surrounding environment without adding any fuel. Because their outer surface is coated with a hydrogel/photocatalyst (chitosan/carbon nitride, C₃N₄) layer, these robots are used for the photocatalytic degradation of the picric acid as an explosive model molecule under visible light. The results show a fast and efficient degradation of picric acid that is attributed to a synergistic effect between the adsorption capability of the chitosan and the photocatalytic activity of C₃N₄ particles. This work provides added insight into the large‐scale fabrication, easy functionalization, and propulsion of tiny robots for environmental applications.     

Magnesium‐Based Micromotors: Water‐Powered Propulsion,Multifunctionality, and Biomedical and Environmental Applications

The new capabilities and functionalities of synthetic micro/nanomotors open up considerable opportunities for diverse environmental and biomedical applications. Water‐powered micromachines are particularly attractive for realizing many of these applications. Magnesium‐based motors directly use water as fuel to generate hydrogen bubbles for their propulsion, eliminating the requirement of common toxic fuels. This Review highlights the development of new Mg‐based micromotors and discusses the chemistry that makes it extremely attractive for micromotor applications. Understanding these Mg properties and its transient nature is essential for controlling the propulsion efficiency, lifetime, and overall performance. The unique and attractive behavior of Mg offers significant advantages, including efficient water‐powered movement, remarkable biocompatibility, controlled degradation, convenient functionalization, and built‐in acid neutralization ability, and has paved the way for multifunctional micromachines for diverse real‐life applications, including operation in living animals. A wide range of such Mg motor‐based applications, including the detection and destruction of environmental threats, effective in‐vivo cargo delivery, and autonomous release, have been demonstrated. In conclusion, the current challenges, future opportunities, and performance improvements of the Mg‐based micromotors are discussed. With continuous innovation and attention to key challenges, it is expected that Mg‐based motors will have a profound impact on diverse biomedical and environmental applications.     

Recent Progress on Bioinspired Self‐Propelled Micro/Nanomotors via Controlled Molecular Self‐Assembly

The combination of bottom‐up controllable self‐assembly technique with bioinspired design has opened new horizons in the development of self‐propelled synthetic micro/nanomotors. Over the past five years, a significant advances toward the construction of bioinspired self‐propelled micro/nanomotors has been witnessed based on the controlled self‐assembly technique. Such a strategy permits the realization of autonomously synthetic motors with engineering features, such as sizes, shapes, composition, propulsion mechanism, and function. The construction, propulsion mechanism, and movement control of synthetic micro/nanomotors in connection with controlled self‐assembly in recent research activities are summarized. These assembled nanomotors are expected to have a tremendous impact on current artificial nanomachines in future and hold potential promise for biomedical applications including drug targeted delivery, photothermal cancer therapy, biodetoxification, treatment of atherosclerosis, artificial insemination, crushing kidney stones, cleaning wounds, and removing blood clots and parasites.     

Erythrocyte–Platelet Hybrid Membrane Coating for Enhanced Nanoparticle Functionalization

Cell‐membrane‐coated nanoparticles have recently been studied extensively for their biological compatibility, retention of cellular properties, and adaptability to a variety of therapeutic and imaging applications. This class of nanoparticles, which has been fabricated with a variety of cell membrane coatings, including those derived from red blood cells (RBCs), platelets, white blood cells, cancer cells, and bacteria, exhibit properties that are characteristic of the source cell. In this study, a new type of biological coating is created by fusing membrane material from two different cells, providing a facile method for further enhancing nanoparticle functionality. As a proof of concept, the development of dual‐membrane‐coated nanoparticles from the fused RBC membrane and platelet membrane is demonstrated. The resulting particles, termed RBC–platelet hybrid membrane‐coated nanoparticles ([RBC‐P]NPs), are thoroughly characterized, and it is shown that they carry properties of both source cells. Further, the [RBC‐P]NP platform exhibits long circulation and suitability for further in vivo exploration. The reported strategy opens the door for the creation of biocompatible, custom‐tailored biomimetic nanoparticles with varying hybrid functionalities, which may be used to overcome the limitations of current nanoparticle‐based therapeutic and imaging platforms.     

Magnetically Powered Annelid‐Worm‐Like Microswimmers

A bioinspired magnetically powered microswimmer is designed and experimentally demonstrated by mimicking the morphology of annelid worms. The structural parameters of the microswimmer, such as the surface wrinkling, can be controlled by applying prestrain on substrate for the precise fabrication and consistent performance of the microswimmers. The resulting annelid‐worm‐like microswimmers display efficient propulsion under an oscillating magnetic field, reaching a peak speed of ≈100 µm s^?1. The speed and directionality of the microswimmer can be readily controlled by changing the parameters of the field inputs. Additionally, it is demonstrated that the microswimmers are able to transport microparticles toward a predefined destination, although the translation velocity is inevitably reduced due to the additional hydrodynamic resistance of the microparticles. These annelid‐worm‐like microswimmers have excellent mobility, good maneuverability, and strong transport capacity, and they hold considerable promise for diverse biomedical, chemical sensing, and environmental applications.     

Micro‐/Nanomotors toward Biomedical Applications: The Recent Progress in Biocompatibility

Inspired by the highly versatile natural motors, artificial micro‐/nanomotors that can convert surrounding energies into mechanical motion and accomplish multiple tasks are devised. In the past few years, micro‐/nanomotors have demonstrated significant potential in biomedicine. However, the practical biomedical applications of these small‐scale devices are still at an infant stage. For successful bench‐to‐bed translation, biocompatibility of micro‐/nanomotor systems is the central issue to be considered. Herein, the recent progress in micro‐/nanomotors in biocompatibility is reviewed, with a special focus on their biomedical applications. Through close collaboration between researches in the nanoengineering, material chemistry, and biomedical fields, it is expected that a promising real‐world application platform based on micro‐/nanomotors will emerge in the near future.     

Magnetically Powered Immunogenic Macrophage Microrobots for Targeted Multimodal Cancer Therapy (Small 42/2023)

Motile microrobots open a new realm for disease treatment. However, the concerns of possible immune elimination, targeted capability and limited therapeutic avenue of microrobots constrain its practical biomedical applications. Herein, a biogenic macrophage-based microrobot loaded with magnetic nanoparticles and bioengineered bacterial outer membrane vesicles (OMVs), capable of magnetic propulsion, tumor targeting, and multimodal cancer therapy is reported. Such cell robots preserve intrinsic properties of macrophages for tumor suppression and targeting, and bioengineered OMVs for antitumor immune regulation and fused anticancer peptides. Cell robots display efficient magnetic propulsion and directional migration in the confined space. In vivo tests show that cell robots can accumulate at the tumor site upon magnetic manipulation, coupling with tumor tropism of macrophages to greatly improve the efficacy of its multimodal therapy, including tumor inhibition of macrophages, immune stimulation, and antitumor peptides of OMVs. This technology offers an attractive avenue to design intelligent medical microrobots with remote manipulation and multifunctional therapy capabilities for practical precision treatment.     

Small‐Scale Machines Driven by External Power Sources

Micro‐ and nanorobots have shown great potential for applications in various fields, including minimally invasive surgery, targeted therapy, cell manipulation, environmental monitoring, and water remediation. Recent progress in the design, fabrication, and operation of these miniaturized devices has greatly enhanced their versatility. In this report, the most recent progress on the manipulation of small‐scale robots based on power sources, such as magnetic fields, light, acoustic waves, electric fields, thermal energy, or combinations of these, is surveyed. The design and propulsion mechanism of micro‐ and nanorobots are the focus of this article. Their fabrication and applications are also briefly discussed.     

A Biomimetic Nanogenerator of Reactive Nitrogen Species Based on Battlefield Transfer Strategy for Enhanced Immunotherapy

Currently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy‐hemoglobin (Hb) dependent drug (RRx‐001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC‐biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx‐001 in hypoxic RBC. Herein, RRx‐001 and Hb are introduced into RBC membrane camouflaged TiO₂ nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx‐001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.     

Recent Progress on Man‐Made Inorganic Nanomachines

The successful development of nanoscale machinery, which can operate with high controllability, high precision, long lifetimes, and tunable driving powers, is pivotal for the realization of future intelligent nanorobots, nanofactories, and advanced biomedical devices. However, the development of nanomachines remains one of the most difficult research areas, largely due to the grand challenges in fabrication of devices with complex components and actuation with desired efficiency, precision, lifetime, and/or environmental friendliness. In this work, the cutting‐edge efforts toward fabricating and actuating various types of nanomachines and their applications are reviewed, with a special focus on nanomotors made from inorganic nanoscale building blocks, which are introduced according to the employed actuation mechanism. The unique characteristics and obstacles for each type of nanomachine are discussed, and perspectives and challenges of this exciting field are presented.     

Light‐Triggered Biomimetic Nanoerythrocyte for Tumor‐Targeted Lung Metastatic Combination Therapy of Malignant Melanoma

Red blood cell (RBC) membrane‐cloaked nanoparticles, reserving the intact cell membrane structure and membrane protein, can gain excellent cell‐specific functions such as long blood circulation and immune escape, providing a promising therapy nanoplatform for drug delivery. Herein, a novel RBC membrane biomimetic combination therapeutic system with tumor targeting ability is constructed by embedding bovine serum albumin (BSA) encapsulated with 1,2‐diaminocyclohexane‐platinum (II) (DACHPt) and indocyanine green (ICG) in the targeting peptide‐modified erythrocyte membrane (R‐RBC@BPtI) for enhancing tumor internalization and synergetic chemophototherapy. R‐RBC@BPtI displays excellent stability and high encapsulation efficiency with multiple cores enveloped in the membrane. Benefited from the stealth functionality and targeting modification of erythrocyte membranes, R‐RBC@BPtI can significantly promote tumor targeting and cellular uptake. Under the near‐infrared laser stimuli, R‐RBC@BPtI presents remarkable instability by singlet oxygen and heat‐mediated cleavage so as to trigger effective drug release, thereby achieving deep penetration and accumulation of DACHPt and ROS in the tumor site. Consequently, R‐RBC@BPtI with tumor‐specific targeting ability accomplishes remarkable ablation of tumors and suppressed lung metastasis in vivo by photothermal and chemotherapy combined ablation under phototriggering. This research provides a novel strategy of targeted biomimetic nanoplatforms for combined cancer chemotherapy–phototherapy.     

Catalytic nanomotors: fabrication,mechanism, and applications

Catalytic nanomotors are nano-to-micrometer-sized actuators that carry an on-board catalyst and convert local chemical fuel in solution into mechanical work. The location of this catalyst as well as the geometry of the structure dictate the swimming behaviors exhibited. The nanomotors can occur naturally in organic molecules, combine natural and artificial parts to form hybrid nanomotors or be purely artificial. Fabrication techniques consist of template directed electroplating, lithography, physical vapor deposition, and other advanced growth methods. Various physical and chemical propulsion mechanisms have been proposed to explain the motion behaviors including diffusiophoresis, bubble propulsion, interfacial tension gradients, and self-electropho-resis. The control and manipulation based upon external fields, catalytic alloys, and motion control through thermal modulation are discussed as well. Catalytic nanomotors represent an exciting technological challenge with the end goal being practical functional nanomachines that can perform a variety of tasks at the nanoscale.     

Motion Control at the Nanoscale

Synthetic nanoscale motors represent a major step in the development of practical nanomachines. This Review summarizes recent progress towards controlling the movement of fuel‐driven nanomotors and discusses the challenges and opportunities associated with the achievement of such nanoscale motion control. Regulating the movement of artificial nanomotors often follows nature's elegant and remarkable approach for motion control. Such on‐demand control of the movement of artificial nanomotors is essential for performing various tasks and diverse applications. These applications require precise control of the nanomotor direction as well as temporal and spatial regulation of the motor speed. Different approaches for controlling the motion of catalytic nanomotors have been developed recently, including magnetic guidance, thermally driven acceleration, an electrochemical switch, and chemical stimuli (including control of the fuel concentration). Such ability to control the directionality of artificial nanomotors and to regulate their speed offers considerable promise for designing powerful nanomachines capable of operating independently and meeting a wide variety of future technological needs.     

Biomimetic and Bioinspired Synthesis of Nanomaterials/Nanostructures

In recent years, due to its unparalleled advantages, the biomimetic and bioinspired synthesis of nanomaterials/nanostructures has drawn increasing interest and attention. Generally, biomimetic synthesis can be conducted either by mimicking the functions of natural materials/structures or by mimicking the biological processes that organisms employ to produce substances or materials. Biomimetic synthesis is therefore divided here into “functional biomimetic synthesis” and “process biomimetic synthesis”. Process biomimetic synthesis is the focus of this review. First, the above two terms are defined and their relationship is discussed. Next different levels of biological processes that can be used for process biomimetic synthesis are compiled. Then the current progress of process biomimetic synthesis is systematically summarized and reviewed from the following five perspectives: i) elementary biomimetic system via biomass templates, ii) high‐level biomimetic system via soft/hard‐combined films, iii) intelligent biomimetic systems via liquid membranes, iv) living‐organism biomimetic systems, and v) macromolecular bioinspired systems. Moreover, for these five biomimetic systems, the synthesis procedures, basic principles, and relationships are discussed, and the challenges that are encountered and directions for further development are considered.     

通用高分子材料的化学和生物改性及其血液相容性研究

功能化与高性能化的通用高分子材料在医用耗材及器械领域有着广泛的应用。作为重要的医用材料之一,血液相容性是首先需要解决的关键科学问题。通用高分子的血液相容性可通过化学和生物修饰来实现。采用的方法大体分为本体改性和表面改性。本体改性主要通过反应接枝和反应共混实现;而表面改性则主要通过在材料表面制备亲水性聚合物刷或亲水层、固定生物活性分子和形成生物仿生膜3种方法来实现。目前,生物材料的血液相容性研究主要集中在血浆蛋白吸附、血小板粘附和红细胞溶血3个方面。结合本课题组近期在生物医用材料领域的研究成果,简要介绍了国内外近年来通用高分子材料的化学和生物改性及其血液相容性研究进展。     

A Review on Artificial Micro/Nanomotors for Cancer-Targeted Delivery,Diagnosis, and Therapy

Micro/nanomotors have been extensively explored for efficient cancer diagnosis and therapy,as evidenced by significant breakthroughs in the design of micro/nanomotors-based intelligent and comprehensive biomedical platforms.Here,we demonstrate the recent advances of micro/nanomotors in the field of cancer-targeted delivery,diagnosis,and imaging-guided therapy,as well as the challenges and problems faced by micro/nanomotors in clinical applications.The outlook for the future development of micro/nanomotors toward clinical applications is also discussed.We hope to highlight these new advances in micro/nanomotors in the field of cancer diagnosis and therapy,with the ultimate goal of stimulating the successful exploration of intelligent micro/nanomotors for future clinical applications.     

Nano‐Gold as Artificial Enzymes: Hidden Talents

Creating artificial enzymes that mimic the complexity and function of natural systems has been a great challenge for the past two decades. In this Progress Report, the focus is on recently discovered “hidden talents” of gold nanomaterials in artificial enzymes, including mimicking of nuclease, esterase, silicatein, glucose oxidase, peroxidase, catalase, and superoxide dismutase. These unexpected enzyme‐like activities can be ascribed to nano‐gold itself or the functional groups present on surrounding monolayer. Along with introducing the mechanisms of the various enzyme‐like activities, the design and development of gold‐based biomimetic catalysts, the search for efficient modulators, and their potential applications in bionics, biosensing, and biomedical sciences are highlighted. Eventually, it is expected that the rapidly growing interest in gold‐based nanozymes will certainly fuel the excitement and stimulate research in this highly active field.