The integration of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhanced anticancer effects. Herein, we report biodegradable cancer cell membrane-coated mesoporous copper/manganese silicate nanospheres (mCMSNs) with homotypic targeting ability to the cancer cell lines and enhanced ROS generation through singlet oxygen ( 1 O 2 ) production and glutathione (GSH)-activated Fenton reaction, showing excellent CDT/PDT synergistic therapeutic effects. We demonstrate that mCMSNs are able to relieve the tumor hypoxia microenvironment by catalytic decomposition of endogenous H 2 O 2 to O 2 and further react with O 2 to produce toxic 1 O 2 with a 635 nm laser irradiation. GSH-triggered mCMSNs biodegradation can simultaneously generate Fenton-like Cu + and Mn 2+ ions and deplete GSH for efficient hydroxyl radical (•OH) production. The specific recognition and homotypic targeting ability to the cancer cells were also revealed. Notably, relieving hypoxia and GSH depletion disrupts the tumor microenvironment (TME) and cellular antioxidant defense system, achieving exceptional cancertargeting therapeutic effects in vitro and in vivo. The cancer cells growth was significantly inhibited. Moreover, the released Mn 2+ can also act as an advanced contrast agent for cancer magnetic resonance imaging (MRI). Thus, together with photosensitizers, Fenton agent provider and MRI contrast effects along with the modulating of the TME allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy. It provides a paradigm to rationally design TMEresponsive and ROS-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effects.

Supporting Videos SI

The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT). Here, we report a H 2 O 2 /O 2 self-supplying nanoagent, (MSNs@CaO 2 -ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO 2 ) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO 2 reacts with water to produce O 2 and H 2 O 2 for hypoxia-relieved ICG-mediated PDT and H 2 O 2 -supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.

Attempts to apply artificial nano/micromotors for diverse biomedical applications have inspired a variety of strategies for designing new motors with unique propulsion mechanisms and functions. However, existing artificial motors are made exclusively of synthetic materials, which are subject to serious immune attack and clearance upon entering the bloodstream. Herein we report an elegant approach that turns natural red blood cells (RBCs) into functional micromotors with the aid of ultrasound propulsion and magnetic guidance. Iron oxide nanoparticles are loaded into the RBCs, where their asymmetric distribution within the cells results in a net magnetization, thus enabling magnetic alignment and guidance under acoustic propulsion. The RBC motors display efficient guided and prolonged propulsion in various biological fluids, including undiluted whole blood. The stability and functionality of the RBC motors, as well as the tolerability of regular RBCs to the ultrasound operation, are carefully examined. Since the RBC motors preserve the biological and structural features of regular RBCs, these motors possess a wide range of antigenic, transport, and mechanical properties that common synthetic motors cannot achieve and thus hold considerable promise for a number of practical biomedical uses.

The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to particular location via dissolution of their enteric coating to activate their propulsion at the target site towards localized tissue penetration and retention.

Efficient and controlled nanoscale propulsion in harsh environments requires careful design and manufacturing of nanomachines, which can harvest and translate the propelling forces with high spatial and time resolution. Here we report a new class of artificial nanomachine, named magneto-acoustic hybrid nanomotor, which displays efficient propulsion in the presence of either magnetic or acoustic fields without adding any chemical fuel. These fuel-free hybrid nanomotors, which comprise a magnetic helical structure and a concave nanorod end, are synthesized using a template-assisted electrochemical deposition process followed by segment-selective chemical etching. Dynamic switching of the propulsion mode with reversal of the movement direction and digital speed regulation are demonstrated on a single nanovehicle. These hybrid nanomotors exhibit a diverse biomimetic collective behavior, including stable aggregation, swarm motion, and swarm vortex, triggered in response to different field inputs. Such adaptive hybrid operation and controlled collective behavior hold considerable promise for designing smart nanovehicles that autonomously reconfigure their operation mode according to their mission or in response to changes in their surrounding environment or in their own performance, thus holding considerable promise for diverse practical biomedical applications of fuel-free 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., H O ), 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.

A red blood cell membrane‐camouflaged nanowire that can serve as new generation of biomimetic motor sponge is described. The biomimetic motor sponge is constructed by the fusion of biocompatible gold nanowire motors and RBC nanovesicles. The motor sponge possesses a high coverage of RBC vesicles, which remain totally functional due to its exclusively oriented extracellular functional portion on the surfaces of motor sponge. These biomimetic motors display efficient acoustical propulsion, including controlled movement in undiluted whole blood. The RBC vesicles on the motor sponge remain highly stable during the propulsion process, conferring thus the ability to absorb membrane‐damaging toxins and allowing the motor sponge to be used as efficient toxin decoys. The efficient propulsion of the motor sponges under an ultrasound field results in accelerated neutralization of the membrane‐damaging toxins. Such motor sponges connect artificial nano­motors with biological entities and hold great promise for treating a variety of injuries and diseases caused by membrane‐damaging toxins.