Collective transport and reconfigurable assembly of nematic colloids by light-driven cooperative molecular reorientations.

Nanomotors in nature have inspired scientists to design synthetic molecular motors to drive the motion of microscale objects by cooperative action. Light-driven molecular motors have been synthesized, but using their cooperative reorganization to control the collective transport of colloids and to realize the reconfiguration of colloidal assembly remains a challenge. In this work, topological vortices are imprinted in the monolayers of azobenzene molecules which further interface with nematic liquid crystals (LCs). The light-driven cooperative reorientations of the azobenzene molecules induce the collective motion of LC molecules and thus the spatiotemporal evolutions of the nematic disclination networks which are defined by the controlled patterns of vortices. Continuum simulations provide physical insight into the morphology change of the disclination networks. When microcolloids are dispersed in the LC medium, the colloidal assembly is not only transported and reconfigured by the collective change of the disclination lines but also controlled by the elastic energy landscape defined by the predesigned orientational patterns. The collective transport and reconfiguration of colloidal assemblies can also be programmed by manipulating the irradiated polarization. This work opens opportunities to design programmable colloidal machines and smart composite materials.

Light-Driven Biomimetic Nanomotors for Enhanced Photothermal Therapy.

Nanotechnology-based strategy has recently drawn extensive attention for the therapy of malignant tumors due to its distinct strengths in cancer diagnosis and treatment. However, the limited intratumoral permeability of nanoparticles is a major hurdle to achieving the desired effect of cancer treatment. Due to their superior cargo towing and reliable penetrating property, micro-/nanomotors (MNMs) are considered as one of the most potential candidates for the coming generation of drug delivery platforms. Here, near-infrared (NIR)-actuated biomimetic nanomotors (4T1-JPGSs-IND) are fabricated successfully and we demonstrate that 4T1-JPGSs-IND selectively accumulate in homologous tumor regions due to the effective homing ability. Upon laser irradiation, hyperthermia generated by 4T1-JPGSs-IND leads to self-thermophoretic motion and photothermal therapy (PTT) to ablate tumors with a deep depth, thereby improving the photothermal therapeutic effect for cancer management. The developed nanomotor system with multifunctionalities exhibits promising potential in biomedical applications to fight against various diseases.

Chemotactic Micro/Nanomotors for Biomedical Applications.

In nature, many organisms respond chemotactically to external chemical stimuli in order to extract nutrients or avoid danger. Inspired by this natural chemotaxis, micro/nanomotors with chemotactic properties have been developed and applied to study a variety of disease models. This chemotactic strategy has shown promising results and has attracted the attention of an increasing number of researchers. This paper mainly reviews the construction methods of different types of chemotactic micro/nanomotors, the mechanism of chemotaxis, and the potential applications in biomedicine. First, based on the classification of materials, the construction methods and therapeutic effects of chemotactic micro/nanomotors based on natural cells and synthetic materials in cellular and animal experiments will be elaborated in detail. Second, the mechanism of chemotaxis of micro/nanomotors is elaborated in detail: chemical reaction induced chemotaxis and physical process driven chemotaxis. In particular, the main differences and significant advantages between chemotactic micro/nanomotors and magnetic, electrical and optical micro/nanomotors are described. The applications of chemotactic micro/nanomotors in the biomedical fields in recent years are then summarized, focusing on the mechanism of action and therapeutic effects in cancer and cardiovascular disease. Finally, the authors are looking forward to the future development of chemotactic micro/nanomotors in the biomedical fields.

Mechanical Efficiency of Photochromic Nanomotors, From First Principles.

Photochromic molecular motors hold promise for a multitude of potential applications in fields ranging from medicine to communications and structural repair. Yet, it is still a challenge to predict their mechanical efficiency. Here, azobenzene is explored as a representative light-driven nanomotor and estimate its quantum yield of photoisomerization and maximum mechanical efficiency. This is based on first-principles mapping of the 3D potential energy surfaces for the ground and excited states of the trans and cis configurations and identifying the minimum energy pathway for isomerization. A work cycle is devised and identifies force constant as the parameter that resembles temperature in the Carnot heat engine, but with very different efficiencies. The results show that the optomechanical efficiency of azobenzene at constant load is about 5% albeit under ideal conditions. To test the hypothesis, the study also explores the optomechanical efficiency of stilbene and 2-butene and shows that their efficiency does not exceed 5%.

Chemically Powered Nanomotors with Magnetically Responsive Function for Targeted Delivery of Exosomes.

Janus structure plays a crucial role in achieving chemically driven nanomotors with exceptional motion performance. However, Janus-structured chemically driven nanomotors with magnetic responsiveness are commonly fabricated by sputtering metal films. In the study, a self-assembly technique is employed to asymmetrically modify the surfaces of magnetic silica (SiO2@Fe3O4) nanoparticles with platinum nanoparticles, resulting in the formation of this kind nanomotors. Compared to platinum film, platinum nanoparticles exhibit a larger surface area and a higher catalytic activity. Hence, the nanomotors demonstrate improved diffusion capabilities at a significantly lower concentration (0.05%) of hydrogen peroxide (H2O2). Meanwhile, exosomes have gained attention as a potential tool for the efficient delivery of biological therapeutic drugs due to their biocompatibility. However, the clinical applications of exosomes are limited by their restricted tropism. The previously obtained nanomotors are utilized to deliver exosomes, greatly enhancing its targetability. The drug doxorubicin (DOX) is subsequently encapsulated within exosomes, acting as a representative drug model. Under the conditions of H2O2 concentration at the tumor site, the exosomes exhibited a significantly enhanced rate of entry into the breast cancer cells. The utilization of the nanomotors for exosomes presents a novel approach in the development of hybrid chemically and magnetically responsive nanomotors.

Buoyancy-Driven Micro/-Nanomotors: From Fundamentals to Applications.

The progression of self-powered micro/-nanomotors (MNMs) has rapidly evolved over the past few decades, showing applications in various fields such as nanotechnology, biomedical engineering, microfluidics, environmental science, and energy harvesting. Miniaturized MNMs transduce chemical/biochemical energies into mechanical motion for navigating through complex fluidic environments with directional control via external forces fields such as magnetic, photonic, and electric stimuli. Among various propulsion mechanisms, buoyancy-driven MNMs have received noteworthy recognition due to their simplicity, efficiency, and versatility. Buoyancy force-driven motors harness the principles of density variation-mediated force to overcome fluidic resistance to navigate through complex environments. Restricting the propulsion in one direction helps to control directional movement, making it more efficient in isotropic solutions. The changes in pH, ionic strength, chemical concentration, solute gradients, or the presence of specific molecules can influence the motion of buoyancy-driven MNMs as evidenced by earlier reports. This review aims to provide a fundamental and detailed analysis of the current state-of-the-art in buoyancy-driven MNMs, aiming to inspire further research and innovation in this promising field.

Swarms of Enzyme-Powered Nanomotors Enhance the Diffusion of Macromolecules in Viscous Media.

Over the past decades, the development of nanoparticles (NPs) to increase the efficiency of clinical treatments has been subject of intense research. Yet, most NPs have been reported to possess low efficacy as their actuation is hindered by biological barriers. For instance, synovial fluid (SF) present in the joints is mainly composed of hyaluronic acid (HA). These viscous media pose a challenge for many applications in nanomedicine, as passive NPs tend to become trapped in complex networks, which reduces their ability to reach the target location. This problem can be addressed by using active NPs (nanomotors, NMs) that are self-propelled by enzymatic reactions, although the development of enzyme-powered NMs, capable of navigating these viscous environments, remains a considerable challenge. Here, the synergistic effects of two NMs troops, namely hyaluronidase NMs (HyaNMs, Troop 1) and urease NMs (UrNMs, Troop 2) are demonstrated. Troop 1 interacts with the SF by reducing its viscosity, thus allowing Troop 2 to swim more easily through the SF. Through their collective motion, Troop 2 increases the diffusion of macromolecules. These results pave the way for more widespread use of enzyme-powered NMs, e.g., for treating joint injuries and improving therapeutic effectiveness compared with traditional methods.

Enzymatic Nanomotors Surviving Harsh Conditions Enabled by Metal Organic Frameworks Encapsulation.

Enzyme-driven micro/nanomotors (MNMs) have demonstrated potentials in the biomedical field because of their excellent biocompatibility, versatility, and fuel bioavailability. However, the fragility of enzymes limits their practical application, because of their susceptibility to denaturation and degradation in realistic scenarios. Herein, a simple yet versatile and effective approach is reported to preserve the enzymatic activity and propulsion capability of enzymatic MNMs under various harsh conditions using metal organic frameworks (MOFs) as a protective shell. Urease can be encapsulated within the exoskeleton of zeolitic imidazolate framework-8 (ZIF-8) via biomimetic mineralization to form ZIF-8@urease (ZU-I) nanomotors that exhibit self-propulsion in the presence of urea. When exposed to harsh conditions, including high temperature, presence of proteases, and organic solvents, the ZU-I nanomotors still maintained their activity and mobility, whereas ZIF-8 with externally modified urease (ZU-O) nanomotors with externally modified urease as a control rapidly lost their motion capabilities owing to the inactivation of urease. Furthermore, ZU-I nanomotors exhibit effectively enhanced diffusion within the small intestine fluid, achieving a fourfold higher mucus penetration than the ZU-O nanomotors. The results highlight the effectiveness of using MOFs as protective shells for enzyme nano-engines, which can greatly advance the practical applications of enzymatic MNMs under realistic conditions, especially for biomedical purpose.

Light-driven rGO/Cu2 + 1O tubular nanomotor with active targeted drug delivery for combination treatment of cancer cells.

The unprecedented navigation ability in micro/nanoscale and tailored functionality tunes micro/nanomotors as new target drug delivery systems, open up new horizons for biomedical applications. Herein, we designed a light-driven rGO/Cu2 + 1O tubular nanomotor for active targeting of cancer cells as a drug delivery system. The propulsion performance is greatly enhanced in real cell media (5% glucose cells isotonic solution), attributing to the introduction of oxygen vacancy and reduced graphene oxide (rGO) layer for separating photo-induced electron-hole pairs. The motion speed and direction can be readily modulated. Meanwhile, doxorubicin (DOX) can be loaded quickly on the rGO layer because of π-π bonding effect. The Cu2 + 1O matrix in the tiny robots not only serves as a photocatalyst to generate a chemical concentration gradient as the driving force but also acts as a nanomedicine to kill cancer cells as well. The strong propulsion of light-driven rGO/Cu2 + 1O nanomotors coupled with tiny size endow them with active transmembrane transport, assisting DOX and Cu2 + 1O breaking through the barrier of the cell membrane. Compared with non-powered nanocarrier and free DOX, light-propelled rGO/Cu2 + 1O nanomotors exhibit greater transmembrane transport efficiency and significant therapeutic efficacy. This proof-of-concept nanomotor design presents an innovative approach against tumor, enlarging the list of biomedical applications of light-driven micro/nanomotors to the superficial tissue treatment.

Light-Switchable Biocatalytic Covalent-Organic Framework Nanomotors for Aqueous Contaminants Removal.

Self-propelled nanomotors represent a promising class of adaptable and versatile technologies with broad applications in the realms of biomedicine and environmental remediation. Herein, we report a biocatalytic nanomotor based on a covalent-organic framework (COF) that demonstrates intelligent and switchable motion triggered by a blue-to-red light switch. Consequently, when exposed to blue light, the nanomotor significantly enhances the removal of contaminants in aqueous solutions due to its elevated mobility. Conversely, it effectively deactivates its motion and contaminant removal upon exposure to red light. This study explores the heterogeneous assembly strategy of the COF-based nanomotor and its light-controlled propulsion performance and provides a novel strategy for the regulation of movement, offering valuable insights for the design and practical applications of nanomotors.

Visualizing Facets Asymmetry Induced Directional Movement of Cadmium Chloride Nanomotor.

Nanomotors in solution have many potential applications. However, it has been a significant challenge to realize the directional motion of nanomotors. Here, we report cadmium chloride tetrahydrate (CdCl2·4H2O) nanomotors with remarkable directional movement under electron beam irradiation. Using in situ liquid phase transmission electron microscopy, we show that the CdCl2·4H2O nanoparticle with asymmetric surface facets moves through the liquid with the flat end in the direction of motion. As the nanomotor morphology changes, the speed of movement also changes. Finite element simulation of the electric field and fluid velocity distribution around the nanomotor assists the understanding of ionic self-diffusiophoresis as a driving force for the nanomotor movement; the nanomotor generates its own local ion concentration gradient due to different chemical reactivities on different facets.

Polyoxometalate-Nanozyme-Integrated Nanomotors (POMotors) for Self-Propulsion-Promoted Synergistic Photothermal-Catalytic Tumor Therapy.

Enzyme-powered nanomotors have demonstrated promising potential in biomedical applications, especially for catalytic tumor therapy, owing to their ability of self-propulsion and bio-catalysis. However, the fragility of natural enzymes limits their environmental adaptability and also therapeutic efficacy in catalysis-enabled tumor therapy. Herein, polyoxometalate-nanozyme-based light-driven nanomotors were designed and synthesized for targeted synergistic photothermal-catalytic tumor therapy. In this construct, the peroxidase-like activity of the P2 W18 Fe4 polyoxometalates-based nanomotors can provide self-propulsion and facilitate their production of reactive oxygen species thus killing tumor cells, even in the weakly acidic tumor microenvironment. Conjugated polydopamine endows the nanomotors with the capability of light-driven self-propulsion behavior. After 10 min of NIR (808 nm) irradiation, along with the help of epidermal growth factor receptor antibody, the targeted accumulation and penetration of nanomotors in the tumor enabled highly efficient synergistic photothermal-catalytic therapy. This approach overcomes the disadvantages of the intrinsically fragile nature of enzyme-powered nanomotors in physiological environments and, more importantly, provides a motility-behavior promoted synergistic anti-tumor strategy.

Supramolecular Modular Assembly of Imaging-Trackable Enzymatic Nanomotors.

Self-propelled micro/nanomotors (MNMs) have shown great application potential in biomedicine, sensing, environmental remediation, etc. In the past decade, various strategies or technologies have been used to prepare and functionalize MNMs. However, the current preparation strategies of the MNMs were mainly following the pre-designed methods based on specific tasks to introduce expected functional parts on the various micro/nanocarriers, which lacks a universal platform and common features, making it difficult to apply to different application scenarios. Here, we have developed a modular assembly strategy based on host-guest chemistry, which enables the on-demand construction of imaging-trackable nanomotors mounted with suitable driving and imaging modules using a universal assembly platform, according to different application scenarios. These assembled nanomotors exhibited enhanced diffusion behavior driven by enzymatic reactions. The loaded imaging functions were used to dynamically trace the swarm motion behavior of assembled nanomotors with corresponding fuel conditions both in vitro and in vivo. The modular assembly strategy endowed with host-guest interaction provides a universal approach to producing multifunctional MNMs in a facile and controllable manner, which paves the way for the future development of MNMs systems with programmable functions.

Lipophilic NO-Driven Nanomotors as Drug Balloon Coating for the Treatment of Atherosclerosis.

Drug-coated balloons (DCB) intervention is an important approach for the treatment of atherosclerosis (AS). However, this therapeutic approach has the drawbacks of poor drug retention and penetration at the lesion site. Here, a lipophilic drug-loaded nanomotor as a modified balloon coating for the treatment of AS is reported. First, a lipophilic nanomotor PMA-TPP/PTX loaded with drug PTX and lipophilic triphenylphosphine (TPP) compounds is synthesized. The PMA-TPP/PTX nanomotors use nitric oxide (NO) as the driving force, which is produced from the reaction between arginine on the motor substrate and excess reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in the AS microenvironment. The final in vitro and in vivo experimental results confirm that the introduction of the lipophilic drug-loaded nanomotor technology can greatly enhance the drug retention and permeability in atherosclerotic lesions. In particular, NO can also play an anti-AS role in improving endothelial cell function and reducing oxidative stress. The chemotherapeutic drug PTX loaded onto the nanomotors can inhibit cell division and proliferation, thereby exerting the effect of inhibiting vascular intimal hyperplasia, which is helpful for the multiple therapies of AS. Using nanomotor technology to solve cardiovascular diseases may be a promising research direction.

Engineered Organic Nanorockets with Light-Driven Ultrafast Transportability for Antitumor Therapy.

Nanomedicines confront various complicated physiological barriers limiting the accumulation and deep penetration in the tumor microenvironment, which seriously restricts the efficacy of antitumor therapy. Self-propelled nanocarriers assembled with kinetic engines can translate external energy into orientated motion for tumor penetration. However, achieving a stable ultrafast permeability at the tumor site remains challenging. Here, sub-200 nm photoactivated completely organic nanorockets (NRs), with asymmetric geometry conveniently assembled from photothermal semiconducting polymer payload and thermo-driven macromolecular propulsion through a straightforward nanoprecipitation process, are presented. The artificial NRs can be remotely manipulated by 808 nm near-infrared light to trigger the photothermal conversion and Curtius rearrangement reaction within the particles for robustly pushing nitrogen out into the solution. Such a two-stage light-to-heat-to-chemical energy transition effectively powers the NRs for an ultrafast (≈300 µm s-1 ) and chemical medium-independent self-propulsion in the liquid media. That endows the NRs with high permeability against physiological barriers in the tumor microenvironment to directionally deliver therapeutic agents to target lesions for elevating tumor accumulation, deep penetration, and cellular uptake, resulting in a significant enhancement of antitumor efficacy. This work will inspire the design of advanced kinetic systems for powering intelligent nanomachines in biomedical applications.

Pressure-Gradient Counterwork of Dual-Fuel Driven Nanocarriers in Abnormal Interstitial Fluids for Enhancing Drug Delivery Efficiency.

The abnormal pressure in tumor tissue is a significant limitation on the drug delivery efficiency of tumor therapy. This work reports a gradient-driven nanomotor as drug nanocarrier with the pressure-counterworking function. The dual-fuel nanomotors are formed by co-electrospinning of the photosensitive polymers with calcium peroxide (CaO2 ) and catalase (CAT), followed by ultraviolet (UV) irradiation and bovine serum albumin (BSA) incubation. The UV-responsive cleavage nanomotors can effectively release O2 molecules at the fractures as a driving force to increase the delivery speed and escape the phagocytosis of macrophage system in normal tissues. Furthermore, CAT catalyzes H2 O2 produced by CaO2 and the tumor interstitial fluids to provide stronger power for the nanomotors. Additionally, according to the analysis of directional motions of the nanomotors, the functional relationship between the rotational diffusion coefficient (DR ) and the physiological viscosity is constructed. The dual-fuel nanocarriers enable up to 13.25% of the injected dose (ID)/per gram tissue and significantly improve the penetration in deep tumor. It is of vital importance to design and obtain the adaptive pressure-gradient counterworking nanomotors, which can effectively improve the drug delivery efficiency in vitro and in vivo.

Periodic Mesoporous Organosilica Nanomaterials with Unconventional Structures and Properties.

Periodic mesoporous organosilicas (PMOs) are high surface area organic-inorganic hybrid nanomaterials that have found broad applications in various fields of research such as in (bio)chemistry or material science. By choosing suitable organic groups in the framework of these materials, their surface properties such as polarity, optical/electrical characteristics and adsorption capacity can be tuned. This critical review provides an overview of the current state of the art in the developments and applications of some PMO nanomaterials in diverse fields of research. This is placed in the context of four leading areas of PMO nanomaterials, including chiral PMOs, plugged PMO nanomaterials, Janus PMOs and PMO-based nanomotors. The review briefly discusses the recent and key findings on these PMO nanomaterials as well as their potential applications for future developments.

Polymeric Bowl-Shaped Nanoparticles: Hollow Structures with a Large Opening on the Surface.

Polymeric bowl-shaped nanoparticles (BNPs) are anisotropic hollow structures with large openings on the surface, which have shown advantages such as high specific area and efficient encapsulation, delivery and release of large-sized cargoes on demand compared to solid nanoparticles or closed hollow structures. Several strategies have been developed to prepare BNPs based on either template or template-free methods. For instance, despite the widely used self-assembly strategy, alternative methods including emulsion polymerization, swelling and freeze-drying of polymeric spheres, and template-assisted approaches have also been developed. It is attractive but still challenging to fabricate BNPs due to their unique structural features. However, there is still no comprehensive summary of BNPs up to now, which significantly hinders the further development of this field. In this review, the recent progress of BNPs will be highlighted from the perspectives of design strategies, preparation methods, formation mechanisms, and emerging applications. Moreover, the future perspectives of BNPs will also be proposed.

Antibacterial micro/nanomotors: advancing biofilm research to support medical applications.

Multi-drug resistant (MDR) bacterial infections are gradually increasing in the global scope, causing a serious burden to patients and society. The formation of bacterial biofilms, which is one of the key reasons for antibiotic resistance, blocks antibiotic penetration by forming a physical barrier. Nano/micro motors (MNMs) are micro-/nanoscale devices capable of performing complex tasks in the bacterial microenvironment by transforming various energy sources (including chemical fuels or external physical fields) into mechanical motion or actuation. This autonomous movement provides significant advantages in breaking through biological barriers and accelerating drug diffusion. In recent years, MNMs with high penetrating power have been used as carriers of antibiotics to overcome bacterial biofilms, enabling efficient drug delivery and improving the therapeutic effectiveness of MDR bacterial infections. Additionally, non-antibiotic antibacterial strategies based on nanomaterials, such as photothermal therapy and photodynamic therapy, are continuously being developed due to their non-invasive nature, high effectiveness, and non-induction of resistance. Therefore, multifunctional MNMs have broad prospects in the treatment of MDR bacterial infections. This review discusses the performance of MNMs in the breakthrough and elimination of bacterial biofilms, as well as their application in the field of anti-infection. Finally, the challenges and future development directions of antibacterial MNMs are introduced.

NIR-II Light Powered Asymmetric Hydrogel Nanomotors for Enhanced Immunochemotherapy.

Nanomotors are appealing drug carriers, and the strength of the propelling force is important for their motion capability. Though high motion efficiency has been achieved with 808 nm light driven Janus-structured noble metal nanomotors, the NIR-I light penetration depth and material biocompatibility limit their broad application. Herein, we develop a 1064 nm NIR-II light driven asymmetric hydrogel nanomotor (AHNM) with high motion capability and load it with doxorubicin for enhanced immunochemotherapy. Magnetic field assisted photopolymerization generates an asymmetric distribution of Fe3 O4 @Cu9 S8 nanoparticles in the AHNM, producing self-thermophoresis as driving force under NIR-II irradiation. The AHNM is also functionalized with dopamine for the capture and retention of tumor-associated antigens to boost immune activation. The as-obtained NIR-II light driven AHNM has a high tumor tissue penetration capability and enhances immunochemotherapy, providing a promising strategy for cancer therapy.