Colorectal cancer remains a major therapeutic challenge due to the immunosuppressive tumor microenvironment and physical barriers that limit drug delivery. Here, we present near-infrared (NIR)-II laser-actuated biomimetic nanorobots (Au-mSiO2@MnCO@SM) designed to overcome these hurdles and potentiate radio-immunotherapy. These nanorobots combine a self-thermophoretic Janus core for active propulsion, a tumor-microenvironment-responsive carbon monoxide (CO) release module for glycolysis suppression and radiosensitization, and a Salmonella membrane coating for enhanced mucus penetration and tumor targeting. Upon reaching tumors, the platform disrupts mitochondrial metabolism, amplifies cytosolic dsDNA via radiation and CO therapy, and releases Mn2+ to synergistically activate the cGAS-STING pathway. This ignites a robust antitumor immune response, complemented by immunogenic cell death. Both in vitro and in vivo experiments demonstrate effective tumor targeting, deep penetration, and significant tumor growth suppression. This work provides a promising and potent strategy for advanced colorectal cancer treatment. Statement of Significance The forbidden biological barriers seriously restrict the delivery efficacy of nanomaterials for treating various major diseases. Herein, we propose orally administrated biomimetic nanorobots with prolonged intestinal retention, enhanced mucus barrier penetration, and tumor-targeting and accumulation characteristics to treat colorectal cancer. By leveraging nanorobot motility, Salmonella-inspired targeting, CO gas-enabled metabolic modulation, and Mn2+-driven cGAS-STING activation, such biomimetic nanorobots can provoke robust radio-immunological responses, which should open a new horizon in the design of nanorobots for radio-immunotherapy.

Radiotherapy is one of the most widely used cancer treatments, but its therapeutic efficacy is often limited by insufficient tumor killing and side effects on surrounding healthy tissues. Radiosensitizers can enhance the sensitivity of tumor cells to ionizing radiation. However, their limited selectivity and penetration into deep tumor tissues due to the complex tumor microenvironment (TME) in solid tumors remain a major obstacle. Nanomotors, which utilize TME conditions to convert chemical energy into mechanical motion, provide a potential solution for enhancing the selectivity and penetration of radiosensitizers into tumors. In this study, we developed cascade catalysis-driven CO@BMON-Au nanomotors, which integrate gold nanoparticles and CO donor within bowl-shaped mesoporous organosilica nanocapsules (BMON). These nanomotors mimic glucose oxidase activity, generating hydrogen peroxide (H2O2) in the presence of glucose and subsequently catalyzing the release of CO, which not only powers the nanomotors for deeper tumor penetration but also sensitizes radiotherapy by mediating mitochondrial and DNA damage via CO therapy. Both in vitro and in vivo experiments demonstrated that the CO gas-driven CO@BMON-Au nanomotors can significantly enhance tumor penetration and improve tumor radiosensitization, offering a promising approach to enhance radiotherapy efficacy.

Radiation-induced injury is a key factor in determining the prognosis of patients undergoing radiotherapy,highlighting the significant clinical importance of developing drugs for radiation prevention and treatment.Especially in oncology,radiation-induced injury remains a pivotal determinant of therapeutic outcomes,because of its direct correlation with normal tissue damage during radiotherapy.Efforts to mitigate or treat such injury are thus paramount in enhancing the overall safety and efficacy of cancer treatment.Novel nanomedicines with prolonged systemic circulation,versatile drug-loading capacities,enhanced tissue retention,and stimuli responsiveness exhibit unique advantages in the treatment and prevention of radiation-induced diseases,as they can be designed based on the specific microenvironment of radiation-damaged tissues,which offers innovative solutions to address the limitations of conventional radioprotectors such as short half-life,poor tissue targeting,and systemic side effects.This review thus aims to provide an overview of recent advance in the design and application of nanomaterials for radiation prevention and treatment.Generally,ionizing radiation damages cells either by inducing DNA double-strand breaks or through the generation of reactive oxygen species(ROS).The resulting oxidative stress would disrupt the structural integrity of cell membranes,proteins,and nucleic acids,leading to apoptosis,chronic inflammation,and systemic effects across multiple systems,including hematopoietic system,gastrointestinal tract,skin,lungs,brain,and heart.Radiation protection strategies focus on scavenging ROS,stimulating cellular repair and regeneration,inducing tissue hypoxia,and inhibiting apoptotic pathways.Recent advances in nanomedicine have introduced novel approaches for targeted and efficient radiation protection and treatment.For radiation-induced hematopoietic injury,nanoparticles can been designed to promote red and white blood cell regeneration while reducing oxidative stress.To address radiation-induced gastrointestinal injuries,nanomaterials enable localized antioxidant delivery and extended intestinal retention,effectively relieving radiation enteritis by scavenging ROS and modulating gut microbiota.For radiation-induced skin injuries,self-assembling peptide hydrogels that mimic the extracellular matrix can serve as effective scaffolds for wound healing.These hydrogels exhibit excellent antioxidant properties,stimulating angiogenesis,and accelerating the recovery of radiation dermatitis.In cases of radiation-induced brain damage,nanoparticles were designed to cross the blood-brain barrier to rescue neuronal damage and protect cognitive function.This review provides an in-depth insight into the mechanisms underlying radiation-induced injuries and highlights how nanomaterial were construtced according to the specific injury.Therefore,nanotechnology endowers durgs with transformative potential for preventing and treating radiation-induced injuries.Despite significant progress in nanomedicine,there are still challenges in long-term biocompatibility,precise targeting of damaged tissues,and scalable manufacturing.In addition,an in-depth understanding of the interactions between nanomaterials and biological systems remains to be covered.Future efforts should focus on optimizing design strategies,enhancing clinical translatability,and ensuring long-term safety,ultimately improving patient outcomes.Besides,expanding research into other radiation-induced diseases,such as radiation-induced ophthalmic disorders and hepatic injuries,may diversify therapeutic options.

Living materials, which include various types of cells, organelles, and biological components from animals, plants, and microorganisms, have become central to recent investigations in micro and nanorobotics. Living material-derived intelligent micro/nanorobots (LMNRs) are self-propelled devices that combine living materials with synthetic materials. By harnessing energy from external physical fields or biological sources, LMNRs can move autonomously and perform various biomedical functions, such as drug delivery, crossing biological barriers, medical imaging, and disease treatment. This review, from a biomimetic strategy perspective, summarized the latest advances in the design and biomedical applications of LMNRs. It provided a comprehensive overview of the living materials used to construct LMNRs, including mammalian cells, plants, and microorganisms while highlighting their biological properties and functions. Lastly, the review discussed the major challenges in this field and offered suggestions for future research that may help facilitate the clinical application of LMNRs in the near future.

Active delivery of therapeutic gases for disease intervention is an appealing but challenging task that requires breakthroughs in nanomaterial-based delivery systems. Micro-/nanomotors (MNMs) capable of efficiently converting diverse forms of energy into mechanical motion have inspired innovations in the gas delivery and therapy domains, offering an alternative possibility to address the challenges of targeted delivery and controlled gas release during therapy. This review thus comprehensively summarizes recent advances in employing MNMs as mobile platforms for precise gas delivery and therapy. The review begins with an introduction of the physiological functions of diverse therapeutic gases, including NO, H2S, CO, O2, and H2. Then various proof-of-concept designs of artificial MNMs that can efficient propulsion in complex biological environments and intelligently release these gases in response to intrinsic or extrinsic stimuli are discussed. Particular emphasis has been placed on their potential in microenvironment modulation for disease treatment, aiming to demonstrate the distinct superiority of MNMs in this area. In addition, the key challenges and limitations of current MNMs utilized for gas therapy are addressed. It is believed that in the near future, MNMs will become sophisticated delivery platforms for facilitating gas therapy.

The application of micro-nano materials in drug delivery has attracted increasing attention. As a photosynthetic group with excellent biocompatibility, microalgae have inherent advantages in this field. These organisms usually show easy-to-process biomass skeletons and remarkable photosynthetic activity, and some species have autonomous mobility. The engineered microalgal system optimizes drug delivery through programmable modifications and achieves auxiliary therapeutic effects through in-situ oxygen generation. This review summarizes the research progress in the use of engineered microalgae for drug delivery, discusses the technical challenges associated with their clinical translation, and provides insights for the design and biomedical application of microalgae-based platforms.

Strain engineering plays an important role in tuning electronic structure and improving catalytic capability of biocatalyst, but it is still challenging to modify the atomic-scale strain for specific enzyme-like reactions. Here, we systematically design Pt single atom (Pt1), several Pt atoms (Ptn) and atomically-resolved Pt clusters (Ptc) on PdAu biocatalysts to investigate the correlation between atomic strain and enzyme-like catalytic activity by experimental technology and in-depth Density Functional Theory calculations. It is found that Ptc on PdAu (Ptc-PA) with reasonable atomic strain upshifts the d-band center and exposes high potential surface, indicating the sufficient active sites to achieve superior biocatalytic performances. Besides, the Pd shell and Au core serve as storage layers providing abundant energetic charge carriers. The Ptc-PA exhibits a prominent peroxidase (POD)-like activity with the catalytic efficiency (Kcat/Km) of 1.50 × 109 mM-1 min-1, about four orders of magnitude higher than natural horseradish peroxidase (HRP), while catalase (CAT)-like and superoxide dismutase (SOD)-like activities of Ptc-PA are also comparable to those of natural enzymes. Biological experiments demonstrate that the detection limit of the Ptc-PA-based catalytic detection system exceeds that of visual inspection by 132-fold in clinical cancer diagnosis. Besides, Ptc-PA can reduce multi-organ acute inflammatory damage and mitigate oxidative stress disorder.

Fluorescence imaging (FLI), a non-invasive, real-time, and highly sensitive imaging modality, allows for investigating the molecular/cellular level activities to understand physiological functions and diseases. The emergence of the second near-infrared window (NIR-II, 1000-1700 nm) has endowed fluorescence imaging with deeper tissue penetration and unprecedented clarity. Among the various NIR-II imaging fluorophores, the organic fluorescent probes have occupied a pivotal position in bioimaging due to their higher biocompatibility, safety, and potential for clinical applications compared with those of the inorganic probes. To obtain high-quality organic dyes, diverse strategies have been taken. In this review, different strategies for optimizing NIR-II organic fluorophores are summarized, including traditional chemical modifications, and emerging bioengineering operations, which have not previously been elaborated on and summarized. Moreover, the bioengineering strategies are highlighted using endogenous serum proteins and even exogenous gene-editing proteins, which would provide fresh insights to design good-performance dyes and help develop NIR-II probes with clinical translation potential in the future. A critical perspective on the direction of the design strategies of NIR-II dyes for disease imaging is also proposed.

Design of engineered cells to target and deliver nanodrugs to the hard-to-reach regions has become an exciting research area. However, the limited penetration and retention of cell-based carriers in tumor tissue restricted their therapeutic efficiency. Inspired by the enhanced delivery behavior of mobile micro/nanomotors, herein, urease-powered platelet cell motors (PLT@Au@Urease) capable of active locomotion, tumor targeting, and radiosensitizers delivery were designed for boosting radiosensitization. The engineered platelet cell motors were constructed by in situ synthesis and loading of radiosensitizers gold nanoparticles in platelets, and then conjugation with urease as the engine. Under physiological concentration of urea, thrust around PLT@Au@Urease motors can be generated via the biocatalytic reactions of urease, leading to rapid tumor cell targeting and enhanced cellular uptake of radiosensitizers. Encouragingly, in comparison with engineered PLT without propulsion capability (PLT@Au), the self-propelled PLT@Au@Urease motors could significantly increase intracellular ROS level and exacerbate nuclear DNA damage induced by gamma-radiation, resulting in a remarkably high sensitization enhancement rate (1.89) than that of PLT@Au (1.08). In vivo experiments with 4 T1-bearing mice demonstrated that PLT@Au@Urease in combination with radiation therapy possessed good antitumor performance. Such an intelligent cell motor would provide a promising approach to enhance radiosensitization and broaden the applications of cell motor-based delivery systems.

Dopamine is the most abundant catecholamine neurotransmitter in the brain and has extensive applications in biomedicine and materials science. Here, novel metal-free fluorescent organic particles (FOPs) with excellent biocompatibility and high photostability, namely DA-PEG-PEI, were successfully synthesized through combination of ring-opening reaction and crosslinking reaction between polyethyleneimine (PEI) and dopamine-containing copolymers (DA-PEGDGE). Because of the crosslink-enhanced emission (CEE) effect of PEI and a quantity of functional groups such as catechol and amines on the surface of the particles, DA-PEG-PEI FOPs possessed high water dispersibility and superior optical properties, making them highly potential for biological imaging applications. Moreover, owing to the existence of functional components/groups, such as amines, catechol groups, the resultant DA-PEG-PEI FOPs can be potentially applied for loading or carrying different bioactive molecules, such as anticancer agent bortezomib, siRNA and CPG oligodeoxynucleotide through formation of dynamic bonds or electrostatic interaction. Furthermore, this reaction can occur under ambient environment, room temperature, in the present of oxygen and without catalysts. Therefore, we believe that this work could not only provide a simple and elegant route for preparation of FOPs, but also have great potential for construction of multifunctional theranostic platforms.

The rapid advances in technology and medicine have greatly facilitated the application of ionizing radiation.Clinically, radiotherapy is one of the major treatments for malignant tumors. However, besides killing tumor cells, ionizing radiation inevitably leads to radiation damage and even death of normal cells. How ionizing radiation causes cell death and the forms of cell death have always been important research topics in this field. Recently, several forms of cell death induced by irradiation have been discovered. Apart from apoptosis, pyroptosis, necroptosis, ferroptosis, autophagic cell death, and methuosis have gradually become research hotspots, and provide new targets for the development of radioprotective drugs and radiosensitizers. In this review, we summarize various forms of ionizing radiation-induced cell death and related molecular mechanisms. We also introduce the latest progress in radiation protection and radiosensitization based on these cell death mechanisms. This review will provide a reference for the research and development of radioprotective drugs and radiosensitizers in the future.

Untethered mobile micro-/nanomotors (MNMs), as newly-emerging attractive and versatile nanotechnologies, are expected to be the next-generation disease treatment tools, for breaking through the limitations of conventional passive drug delivery manner. However, the advances in these fascinating platforms have been hampered by the complexity of the biological environment and the particularity of disease microenvironment. Consequently, specific design strategies and clinical imaging techniques are essential to ensure the high-efficiency of biomedical MNMs on actuation, targeting, localization, and therapy when performing assigned in vivo tasks. This review thus comprehensively addresses three aspects of biomedical MNMs, including design, imaging, and disease treatment, highlighting the intelligent MNMs with biomimetic functionality and chemotactic capability, emphasizing the applicability of different imaging techniques, and focusing on various proof-of-concept studies based on physiological characteristics for the treatment of major diseases. In addition, the key challenges and limitations of current biomedical MNMs are addressed, which may inspire future research and facilitate translation toward clinical treatment.

Selenium (Se) and tellurium (Te) nanomaterials with novel chain-like structures have attracted widespread interest owing to their intriguing properties. Unfortunately, the still-unclear catalytic mechanisms have severely limited the development of biocatalytic performance. In this work, we developed chitosan-coated Se nanozymes with a 23-fold higher antioxidative activity than Trolox and bovine serum albumin coated Te nanozymes with stronger prooxidative biocatalytic effects. Based on density functional theory calculations, we first propose that the Se nanozyme with Se/Se2- active centers favored reactive oxygen species (ROS) clearance via a LUMO-mediated mechanism, while the Te nanozyme with Te/Te4+ active centers promoted ROS production through a HOMO-mediated mechanism. Furthermore, biological experiments confirmed that the survival rate of γ-irritated mice treated with the Se nanozyme was maintained at 100% for 30 days by inhibiting oxidation. However, the Te nanozyme had the opposite biological effect via promoting radiation oxidation. The present work provides a new strategy for improving the catalytic activities of Se and Te nanozymes.

微纳米马达是能将环境中的化学反应或外场(光、声、磁场、电场等)提供的能量转化为推进力,从而产生自主运动的微纳米级人造机器.由于具有集群效应、比表面积大、运动可控等多种特征,微纳米马达在环境修复、药物递送、微纳手术、抗感染、重金属清除等诸多领域受到关注.在一定条件下,微纳米马达能主动运动并聚集到病灶,将治疗或诊断药物递送到靶部位,有望在人体复杂环境中进行精细化的工作.因此,微纳米马达在疾病预防、诊断、治疗以及预后中具有巨大的发展空间.在此,本文首先简要介绍微纳米马达的结构设计、驱动方式;其次,详细介绍微纳米马达在不同类型的疾病中的研究进展;最后,提出目前该技术面临的挑战与未来发展方向.

As a member of nano-carbon compound, nanodiamonds (ND) with diverse structure, small size and relative low toxicity has been extensively explored for different applications especially as delivery vehicles for drugs. However, surface functionalization of ND with polymers is still required to overcome their poor water dispersibility and improve drug delivery performance. In this work, we reported a simple photocatalytic atom transfer radical polymerization (ATRP) method for surface functionalization of ND by using FeBr3 as the photoredox catalyst. Owing to the introduction of water dispersible 2-methacryloyloxyethyl phosphorylcholine (MPC), resultant NDs-MPC displayed improved water dispersibility and low toxicity. The anticancer agent DOX could be loaded on NDs-MPC efficiently and controlled release from ND-P-DOX complexes. The cell viability and cell imaging results demonstrated that DOX can be transported into cells and maintained its corresponding therapeutic effect. More importantly, as compared with traditional ATRP, photocatalytic ATRP could not only operate under rather mild conditions but also could avoid utilization of expensive and toxic agents. Considered the advantages of photocatalytic ATRP and ND, the method developed in this work could be a promising strategy for fabrication of multifunctional ND-based composites for different applications.

Chitosan is an abundant natural polysaccharide that contains a lot of amino and hydroxyl groups. It possesses great potential for biomedical applications owing to its low toxicity, biodegradability and low cost. Herein, a novel chitosan-based fluorescent copolymer (WS-CS-TPA) was designed and synthesized via nucleophilic substitution of hexachlorocyclotriphosphazene (HCCP), water-soluble chitosan (WS-CS) and an aggregation-induced emission (AIE) fluorogen (AIEgen) triphenylamine derivative (TPA-NH2). Under ultrasonic treatment, 1.16 g TPA-NH2 and 1.1 g WS-CS can be conjugated by 0.7 g HCCP at room temperature. The obtained copolymer shows amphiphilic property and could assemble into nanoparticles with size about 100 nm. After self-assembly, TPANH2 was aggregated in the core, thus exhibiting superb AIE feature with intense green fluorescence emission in aqueous media. On the other hand, hydrophilic WS-CS was coated on the surface of nanoparticles and endowed their high water dispersibility. Results from preliminary biological assays suggested that WS-CS-TPA can be internalized by cells and exhibits low cytotoxicity, suggesting their great potential for biological imaging and intracellular drug delivery.

In this paper, a simple method that relied on direct chain transfer free radical polymerization was reported to synthesize MSNs based polymeric composites (named as MCM-41-SH-poly (PEGMA-co-VPA)) using poly (ethylene glycol) monomethyl ether (PEGMA) and 4-vinyl phenylboric acid (VPA) as monomers. The utilization of MCM-41-SH-poly (PEGMA-co-VPA) to load and delivery curcumin (CUR) was also evaluated in detail. The structure, properties, drug loading and release behaviors were evidenced by various characterization techniques. The results from biological studies have shown that CUR can be effectively loaded on MCM-41-SH-poly (PEGMA-co-VPA) with high drug loading rate through formation of borate bond between CUR and VPA. More importantly, resultant drug-loading complexes displayed excellent water dispersibility and CUR could be released from complexes with pH responsiveness. Taken together, we have developed a simple method for surface modification MCM-41 and resultant composites could display improved properties for intracellular controlled drug delivery applications. (C) 2021 Elsevier B.V. All rights reserved.

Modulation of radiation biological process at atomic and molecular level is closely related to biocatalytic process, redox biology and multisystem inflammation. Thus, it is necessary to clarify the exact relationship between the biocatalytic process and radiation biology, and further establish the corresponding intrinsic mechanism. In this work, we employed a serial of single atom substitutional gold clusters, which show different biocatalytic activity and selectivity for radiation induced redox modulation. The single atomic Er-substituted Au clusters show the highest antioxidant activity, and clearance rate to reactive oxygen and nitrogen species (RONS), such as peroxynitrite (ONOO-), nitric oxide ((NO)-N-center dot) and hydroxyl radicals ((OH)-O-center dot). Meanwhile, single atomic Cu- or Pt-substituted Au clusters exhibit excellent catalase-like (CAT-like) activity. Moreover, the single atomic Pt-substituted Au clusters also show the best ability to oxidate H2O molecules to OH-. Biological experiments show that Er-substituted Au clusters have good radioreduction ability, which can increase the survival rate of irradiated mice from 40% to 90%. On the contrary, Au clusters substituted by Cu or Pt have the effect of promoting radioxidation, reducing the survival rate of mice to 30% and 0%. These results suggest that antioxidant capacity, RONS scavenging ability and reducibility are closely related to radioreduction, while CAT-like activity and oxidativeness promote radioxidation.

Superoxide dismutase (SOD) is one of the major antioxidants in vivo and is expected to play critical roles on the defense against reactive oxygen species (ROS)-mediated damages, such as ionizing radiation damages. Herein, inspired by the function and structure of natural SODs and cerium oxide nanozymes, two monovalent cerium-based metal organic frameworks (Ce-MOFs), CeIIIBTC and CeIVBTC, were designed for superoxide radical (O2•-) elimination and ionizing radiation protection. These two Ce-MOFs selectively scavenge O2•- and are excellent SOD mimics. Like natural SODs and cerium oxide nanozymes, the SOD-like catalytic mechanism of Ce-MOFs involves a cycle between Ce(IV) and Ce(III). Furthermore, by constructing monovalent Ce-MOFs, we found that high-valent CeIVBTC are more effective SOD-like nanozymes compared to CeIIIBTC. With smaller size, better monodispersity, and more effective SOD-like activity, CeIVBTC nanozymes were further applied for ionizing radiation protection. Both in vitro and in vivo results demonstrated that CeIVBTC nanozymes could efficiently scavenge ROS, prevent cells from γ-ray radiation-induced cell viability decrease and DNA damages, and improve the survival rate of irradiated mice by recovering the bone marrow DNA damage and alleviating oxidative stress of tissues. The protective effect and good biocompatibility of CeIVBTC nanozymes will enable the development of Ce-MOFs-based radioprotectants and facilitate treatment of other ROS-related diseases.

In recent 20 years, the functional materials with aggregation-induced emission (ALE) feature have shown huge superiority and great potential in biomedicine field and numerous strategies have been developed to fabricate these ALE-active functional materials. Though delightful developments, facile synthesis of inorganic-organic hybrid fluorescent nanoparticles with AIE feature has seldom reported thus far. In this work, we reported for the first time that novel cross-linked inorganic-organic hybrid polyphosphazene nanospheres with AIE feature could be simply synthesized via conjugation ALE-active fluorophore tetraphenylethylene derivative (TPE-NH 2 ) with hydrophilic polyethylene glycol (PEG-NH2) using hexachlorocyclotriphosphazene (HCCP) as the bridge. This strategy is simple and high-efficient with some advantages (e.g., the reaction can occur under room temperature, the reaction time is short, no surfactant is required and no air-protection is needed). The structure, morphology and spectroscopic properties of TPE-HCCP-PEG nanoparticles (NPs) were characterized by various apparatus. To further evaluate their potential applications in biomedical fields, biocompatibility and cell uptake behavior of TPE-HCCP-PEG composites have been examined. Results demonstrated that TPE-HCCP-PEG NPs possessed intensive fluorescence and high water dispersibility and were of low cytotoxicity. These features endow TPE-HCCP-PEG NPs huge potential in fluorescence imaging. Also, the strategy can be extended for the construction of many other inorganic-organic hybrid polymers taken advantage of their unique features and convenient synthetic method. We expect that this work will open a new avenue for the synthesis of inorganic heterocycles centered ALE-active materials with extensive application prospects. (C) 2021 Elsevier B.V. All rights reserved.