Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment.

Cancer, as one of the leading causes of death worldwide, drives the advancement of cutting-edge technologies for cancer treatment. Transition-metal-based nanozymes emerge as promising therapeutic nanodrugs that provide a reference for cancer therapy. In this review, we present recent breakthrough nanozymes for cancer treatment. First, we comprehensively outline the preparation strategies involved in creating transition-metal-based nanozymes, including hydrothermal method, solvothermal method, chemical reduction method, biomimetic mineralization method, and sol-gel method. Subsequently, we elucidate the catalytic mechanisms (catalase (CAT)-like activities), peroxidase (POD)-like activities), oxidase (OXD)-like activities) and superoxide dismutase (SOD)-like activities) of transition-metal-based nanozymes along with their activity regulation strategies such as morphology control, size manipulation, modulation, composition adjustment and surface modification under environmental stimulation. Furthermore, we elaborate on the diverse applications of transition-metal-based nanozymes in anticancer therapies encompassing radiotherapy (RT), chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), immunotherapy, and synergistic therapy. Finally, the challenges faced by transition-metal-based nanozymes are discussed alongside future research directions. The purpose of this review is to offer scientific guidance that will enhance the clinical applications of nanozymes based on transition metals.

Engineering Nanoplatforms for Theranostics of Atherosclerotic Plaques.

Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post-interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal-to-noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis are comprehensively summarized. Additionally, several therapeutic strategies are proposed to enhance the efficacy of treating atherosclerotic plaques. Finally, existing challenges and promising prospects for accelerating clinical translation of nanoplatform-based molecular imaging and therapy for atherosclerotic plaques are discussed. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques.

Magneto-optical nanosystems for tumor multimodal imaging and therapy in-vivo.

Multimodal imaging, which combines the strengths of two or more imaging modalities to provide complementary anatomical and molecular information, has emerged as a robust technology for enhancing diagnostic sensitivity and accuracy, as well as improving treatment monitoring. Moreover, the application of multimodal imaging in guiding precision tumor treatment can prevent under- or over-treatment, thereby maximizing the benefits for tumor patients. In recent years, several intriguing magneto-optical nanosystems with both magnetic and optical properties have been developed, leading to significant breakthroughs in the field of multimodal imaging and image-guided tumor therapy. These advancements pave the way for precise tumor medicine. This review summarizes various types of magneto-optical nanosystems developed recently and describes their applications as probes for multimodal imaging and agents for image-guided therapeutic interventions. Finally, future research and development prospects of magneto-optical nanosystems are discussed along with an outlook on their further applications in the biomedical field.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

Activatable Probes for Ratiometric Imaging of Endogenous Biomarkers In Vivo.

Dynamic variations in the concentration and abnormal distribution of endogenous biomarkers are strongly associated with multiple physiological and pathological states. Therefore, it is crucial to design imaging systems capable of real-time detection of dynamic changes in biomarkers for the accurate diagnosis and effective treatment of diseases. Recently, ratiometric imaging has emerged as a widely used technique for sensing and imaging of biomarkers due to its advantage of circumventing the limitations inherent to conventional intensity-dependent signal readout methods while also providing built-in self-calibration for signal correction. Here, the recent progress of ratiometric probes and their applications in sensing and imaging of biomarkers are outlined. Ratiometric probes are classified according to their imaging mechanisms, and ratiometric photoacoustic imaging, ratiometric optical imaging including photoluminescence imaging and self-luminescence imaging, ratiometric magnetic resonance imaging, and dual-modal ratiometric imaging are discussed. The applications of ratiometric probes in the sensing and imaging of biomarkers such as pH, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), gas molecules, enzymes, metal ions, and hypoxia are discussed in detail. Additionally, this Review presents an overview of challenges faced in this field along with future research directions.

Nanomaterials for Disease Treatment by Modulating the Pyroptosis Pathway.

Pyroptosis differs significantly from apoptosis and cell necrosis as an alternative mode of programmed cell death. Its occurrence is mediated by the gasdermin protein, leading to characteristic outcomes including cell swelling, membrane perforation, and release of cell contents. Research underscores the role of pyroptosis in the etiology and progression of many diseases, making it a focus of research intervention as scientists explore ways to regulate pyroptosis pathways in disease management. Despite numerous reviews detailing the relationship between pyroptosis and disease mechanisms, few delve into recent advancements in nanomaterials as a mechanism for modulating the pyroptosis pathway to mitigate disease effects. Therefore, there is an urgent need to fill this gap and elucidate the path for the use of this promising technology in the field of disease treatment. This review article delves into recent developments in nanomaterials for disease management through pyroptosis modulation, details the mechanisms by which drugs interact with pyroptosis pathways, and highlights the promise that nanomaterial research holds in driving forward disease treatment.

Stimuli-Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy.

Radiotherapy (RT) has been a classical therapeutic method of cancer for several decades. It attracts tremendous attention for the precise and efficient treatment of local tumors with stimuli-responsive nanomaterials, which enhance RT. However, there are few systematic reviews summarizing the newly emerging stimuli-responsive mechanisms and strategies used for tumor radio-sensitization. Hence, this review provides a comprehensive overview of recently reported studies on stimuli-responsive nanomaterials for radio-sensitization. It includes four different approaches for sensitized RT, namely endogenous response, exogenous response, dual stimuli-response, and multi stimuli-response. Endogenous response involves various stimuli such as pH, hypoxia, GSH, and reactive oxygen species (ROS), and enzymes. On the other hand, exogenous response encompasses X-ray, light, and ultrasound. Dual stimuli-response combines pH/enzyme, pH/ultrasound, and ROS/light. Lastly, multi stimuli-response involves the combination of pH/ROS/GSH and X-ray/ROS/GSH. By elaborating on these responsive mechanisms and applying them to clinical RT diagnosis and treatment, these methods can enhance radiosensitive efficiency and minimize damage to surrounding normal tissues. Finally, this review discusses the additional challenges and perspectives related to stimuli-responsive nanomaterials for tumor radio-sensitization.

Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics.

Stimuli-responsive polymers can respond to internal stimuli, such as reactive oxygen species (ROS), glutathione (GSH), and pH, biological stimuli, such as enzymes, and external stimuli, such as lasers and ultrasound, etc., by changing their hydrophobicity/hydrophilicity, degradability, ionizability, etc., and thus have been widely used in biomedical applications. Due to the characteristics of the tumor microenvironment (TME), stimuli-responsive polymers that cater specifically to the TME have been extensively used to prepare smart nanovehicles for the targeted delivery of therapeutic and diagnostic agents to tumor tissues. Compared to conventional drug delivery nanosystems, TME-responsive nanosystems have many advantages, such as high sensitivity, broad applicability among different tumors, functional versatility, and improved biosafety. In recent years, a great deal of research has been devoted to engineering efficient stimuli-responsive polymeric nanosystems, and significant improvement has been made to both cancer diagnosis and therapy. In this review, we summarize some recent research advances involving the use of stimuli-responsive polymer nanocarriers in drug delivery, tumor imaging, therapy, and theranostics. Various chemical stimuli will be described in the context of stimuli-responsive nanosystems. Accordingly, the functional chemical groups responsible for the responsiveness and the strategies to incorporate these groups into the polymer will be discussed in detail. With the research on this topic expending at a fast pace, some innovative concepts, such as sequential and cascade drug release, NIR-II imaging, and multifunctional formulations, have emerged as popular strategies for enhanced performance, which will also be included here with up-to-date illustrations. We hope that this review will offer valuable insights for the selection and optimization of stimuli-responsive polymers to help accelerate their future applications in cancer diagnosis and treatment.

Self-Reporting Molecular Prodrug for In Situ Quantitative Sensing of Drug Release by Ratiometric Photoacoustic Imaging.

Understanding the pharmacokinetics of prodrugs in vivo necessitates quantitative, noninvasive, and real-time monitoring of drug release, despite its difficulty. Ratiometric photoacoustic (PA) imaging, a promising deep tissue imaging technology with a unique capacity for self-calibration, can aid in solving this problem. Here, for the first time, a methylamino-substituted Aza-BODIPY (BDP-N) and the chemotherapeutic drug camptothecin (CPT) are joined via a disulfide chain to produce the molecular theranostic prodrug (BSC) for real-time tumor mapping and quantitative visualization of intratumoral drug release using ratiometric PA imaging. Intact BSC has an extremely low toxicity, with a maximum absorption at ∼720 nm; however, endogenous glutathione (GSH), which is overexpressed in tumors, will cleave the disulfide bond and liberate CPT (with full toxicity) and BDP-N. This is accompanied by a significant redshift in absorption at ∼800 nm, resulting in the PA800/PA720 ratio. In vitro, a linear relationship is successfully established between PA800/PA720 values and CPT release rates, and subsequent experiments demonstrate that this relationship can also be applied to the quantitative detection of intratumoral CPT release in vivo. Notably, the novel ratiometric strategy eliminates nonresponsive interference and amplifies the multiples of the signal response to significantly improve the imaging contrast and detection precision. Therefore, this research offers a viable alternative for the design of molecular theranostic agents for the clinical diagnosis and treatment of tumors.

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.

Anatase TiO2-x and zwitterionic porphyrin polymer-based nanocomposite for enhanced cancer photodynamic therapy.

Photodynamic therapy has been used as a treatment option for cancer; however, the existing TiO2 photosensitizer does not have the ability to specifically target cancer cells. This lack of selectivity reduces its effectiveness in overcoming cancer resistance. To improve photodynamic therapy outcomes, an innovative solution is proposed. In this study, we report on the compounding of a zwitterionic covalent organic polymer (COP) with a TiO2 photosensitizer for the first time. The aim is to overcome cancer cellular resistance. A one-pot synthetic strategy, which includes the construction of a porphyrin-based COP has been employed. This strategy has also been applied to the rapid preparation of anatase defective TiO2 (TiO2-x). To improve the hydrophilic and antifouling properties of the polymer, zwitterion L-cysteine has been conjugated with a porphyrin-based COP using a thiol-ene "click chemistry" reaction. The novel zwitterionic porphyrin-based COP has the ability to trigger biodegradation under the acid microenvironment due to the presence of acid-sensitive ß-thioether esters. When combined with TiO2-x, the resultant nanocomposite produces an enhanced photodynamic therapy effect for drug-resistant cancer cells under NIR laser irradiation. This is due to the strong mutual sensitization of zwitterionic porphyrin-based COP and TiO2-x. Importantly, the nanocomposite delivery system exhibits excellent cytocompatibility in the dark and has the potential to improve the accuracy of cancer diagnosis through fluorescence imaging. The results of this study demonstrate the potential application of this alternative nanocomposite delivery system for remote-controllable photodynamic therapy of tumors.

Stimuli responsive nanosonosensitizers for sonodynamic therapy.

Sonodynamic therapy (SDT) has gained significant attention in the treatment of deep tumors and multidrug-resistant (MDR) bacterial infections due to its high tissue penetration depth, high spatiotemporal selectivity, and noninvasive therapeutic method. SDT combines low-intensity ultrasound (US) and sonosensitizers to produce lethal reactive oxygen species (ROS) and external damage, which is the main mechanism behind this therapy. However, traditional organic small-molecule sonosensitizers display poor water solubility, strong phototoxicity, and insufficient targeting ability. Inorganic sonosensitizers, on the other hand, have low ROS yield and poor biocompatibility. These drawbacks have hindered SDT's clinical transformation and application. Hence, designing stimuli-responsive nano-sonosensitizers that make use of the lesion's local microenvironment characteristics and US stimulation is an excellent alternative for achieving efficient, specific, and safe treatment. In this review, we provide a comprehensive overview of the currently accepted mechanisms in SDT and discuss the application of responsive nano-sonosensitizers in the treatment of tumor and bacterial infections. Additionally, we emphasize the significance of the principle and process of response, based on the classification of response patterns. Finally, this review emphasizes the potential limitations and future perspectives of SDT that need to be addressed to promote its clinical transformation.

Ratiometric optical probes for biosensing.

Biosensing by optical probes is bringing about a revolution in our understanding of physiological and pathological states. Conventional optical probes for biosensing are prone to inaccurate detection results due to various analyte-independent factors that can lead to fluctuations in the absolute signal intensity. Ratiometric optical probes provide built-in self-calibration signal correction for more sensitive and reliable detection. Probes specifically developed for ratiometric optical detection have been shown to significantly improve the sensitivity and accuracy of biosensing. In this review, we focus on the advancements and sensing mechanism of ratiometric optical probes including photoacoustic (PA) probes, fluorescence (FL) probes, bioluminescence (BL) probes, chemiluminescence (CL) probes and afterglow probes. The versatile design strategies of these ratiometric optical probes are discussed along with a broad range of applications for biosensing such as sensing of pH, enzymes, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), metal ions, gas molecules and hypoxia factors, as well as the fluorescence resonance energy transfer (FRET)-based ratiometric probes for immunoassay biosensing. Finally, challenges and perspectives are discussed.

Construction of rolling circle amplification products-based pure nucleic acid nanostructures for biomedical applications.

Nucleic acid nanomaterials with good biocompatibility, biodegradability, and programmability have important applications in biomedical field. Nucleic acid nanomaterials are usually combined with some inorganic nanomaterials to improve their biological stability. However, undefined toxic side effects of composite nanocarriers hamper their application in vivo. As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. RCA products with different functional parts can be customized by changing the sequence of the circular template, thereby generating complex multifunctional DNA nanostructures, such as DNA nanowire, nanoflower, origami, nanotube, nanoribbon, etc. More importantly, RCA products as nonnicked building blocks can enhance the biostability of DNA nanostructures, especially in vivo. These RCA products-based nucleic acid nanostructures can be used as scaffolds or nanocarriers to interact or load with metal nanoparticles, proteins, lipids, cationic polymers, therapeutic nucleic acids or drugs, etc. This paper reviews the assembly strategies of RCA based DNA nanostructures with different shape and their applications in biosensing, bioimaging and biomedicine. Finally, the development prospects of the nucleic acid nanomaterials in clinical diagnosis and treatment of diseases are described. STATEMENT OF SIGNIFICANCE: As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. This paper reviews the construction of various shapes of pure nucleic acid nanomaterials based on RCA products and their applications in biosensing, bioimaging and biomedicine. This will promote the development of biocompatible DNA nanovehicles and their further application in living systems, including bioimaging, molecular detection, disease diagnosis and drug delivery, finally producing a significant impact in the field of nanotechnology and nanomedicine.

Nanomaterial-based CT contrast agents and their applications in image-guided therapy.

Computed tomography (CT), a diagnostic tool with clinical application, comprehensive coverage, and low cost, is used in hospitals worldwide. However, CT imaging fails to distinguish soft tissues from normal organs and tumors because their mass attenuation coefficients are similar. Various CT contrast agents have been developed in recent years to improve the sensitivity and contrast of imaging. Here, we review the progress of nanomaterial-based CT contrast agents and their applications in image-guided therapy. The CT contrast agents are classified according to their components; gold (Au)-based, bismuth (Bi)-based, lanthanide (Ln)-based, and transition metal (TM)-based nanomaterials are discussed. CT image-guided therapy of diseases, including photothermal therapy (PPT), photodynamic therapy (PDT), chemotherapy, radiotherapy (RT), gas therapy, sonodynamic therapy (SDT), immunotherapy, starvation therapy, gene therapy (GT), and microwave thermal therapy (MWTT), are reviewed. Finally, the perspectives on the CT contrast agents and their biomedical applications are discussed.

Plasmon enhanced catalysis-driven nanomotors with autonomous navigation for deep cancer imaging and enhanced radiotherapy.

Radiosensitizers potentiate the radiotherapy effect while effectively reducing the damage to healthy tissues. However, limited sample accumulation efficiency and low radiation energy deposition in the tumor significantly reduce the therapeutic effect. Herein, we developed multifunctional photocatalysis-powered dandelion-like nanomotors composed of amorphous TiO2 components and Au nanorods (∼93 nm in length and ∼16 nm in outer diameter) by a ligand-mediated interface regulation strategy for NIR-II photoacoustic imaging-guided synergistically enhanced cancer radiotherapy. The non-centrosymmetric nanostructure generates stronger local plasmonic near-fields close to the Au-TiO2 interface. Moreover, the Au-TiO2 Schottky heterojunction greatly facilitates the separation of photogenerated electron-hole pairs, enabling hot electron injection, finally leading to highly efficient plasmon-enhanced photocatalytic activity. The nanomotors exhibit superior motility both in vitro and in vivo, propelled by H2 generated via NIR-catalysis on one side of the Au nanorod, which prevents them from returning to circulation and effectively improves the sample accumulation in the tumor. Additionally, a high radiation dose deposition in the form of more hydroxyl radical generation and glutathione depletion is authenticated. Thus, synergistically enhanced radiotherapeutic efficacy is achieved in both a subcutaneous tumor model and an orthotopic model.

Spatiotemporally Controlled Formation and Rotation of Magnetic Nanochains In Vivo for Precise Mechanotherapy of Tumors.

Systemic cancer therapy is always accompanied with toxicity to normal tissue, which has prompted concerted efforts to develop precise treatment strategies. Herein, we firstly develop an approach that enables spatiotemporally controlled formation and rotation of magnetic nanochains in vivo, allowing for precise mechanotherapy of tumor. The nanochain comprised nanocomposites of pheophorbide-A (PP) modified iron oxide nanoparticle (IONP) and lanthanide-doped down-conversion NP (DCNP). In a permanent magnetic field, the nanocomposites would be aligned to form nanochain. Next, MnO2 NPs were subsequently administered to accumulate in tumor as suppliers of Mn2+ , which coordinates with PP to immobilize the nanochain. In a rotating magnetic field, the nanochain would rapidly rotate, leading to apoptosis/necrosis of tumor cell. The nanochain showed high T2 -MR and NIR-II fluorescence imaging signals, which facilitated guided therapy. The strategy has great potential in practical applications.

Activatable Nanoprobe with Aggregation-Induced Dual Fluorescence and Photoacoustic Signal Enhancement for Tumor Precision Imaging and Radiotherapy.

Owing to the high sensitivity and high spatial resolution, fluorescence (FL) imaging has been widely applied for visualizing biological processes. To gain insight into molecular events on deeper tissues, photoacoustic (PA) imaging with better deep-tissue imaging capability can be incorporated to provide complementary visualization and quantitative information on the pathological status. However, the development of activatable imaging probes to achieve both FL and PA signal amplification remains challenging because the enhancement of light absorption in PA imaging often caused the quenching of FL signal. Herein, we first developed a caspase-3 enzyme activatable nanoprobe of a nanogapped gold nanoparticle coated with AIE molecule INT20 and DEVD peptides (AuNNP@DEVD-INT20) for tumor FL and PA imaging and subsequent imaging-guided radiotherapy. The nanoprobe could interact with GSH and caspase-3 enzyme to liberate INT20 molecules, leading to AIE. Simultaneously, the in situ self-assembly of AuNPs was achieved through the cross-linking reaction between the sulfhydryl and the maleimide, resulting in ratiometric PA imaging in tumor. Remarkably, the nanoprobe can generate richful ROS for cancer radiotherapy under X-ray irradiation. The platform not only achieves the aggregation-induced FL and PA signal enhancement but also provides a general strategy for imaging of various biomarkers, eventually benefiting precise cancer therapy.

NIR-II Functional Materials for Photoacoustic Theranostics.

Photoacoustic imaging (PAI) has attracted great attention in the diagnosis and treatment of diseases due to its noninvasive properties. Especially in the second near-infrared (NIR-II) window, PAI can effectively avoid the interference of tissue spontaneous fluorescence and light scattering, and obtain high resolution images with deeper penetration depth. Because of its ideal spectral absorption and high conversion efficiency, NIR-II PA contrast agents overcome the absorption or emission of NIR-II light by endogenous biomolecules. In recent years, a series of NIR-II PA contrast agents have been developed to improve the performance of PAI in disease diagnosis and treatment. In this paper, the research progress of NIR-II PA contrast agents and their applications in biomedicine are reviewed. PA contrast agents are classified according to their composition, including inorganic contrast agents, organic contrast agents, and hybrid organic-inorganic contrast agents. The applications of NIR-II PA contrast agents in medical imaging are described, such as cancer imaging, inflammation detection, brain disease imaging, blood related disease imaging, and other biomedical application. Finally, the research prospects and breakthrough of NIR-II PA contrast agents are discussed.

Neodymium (3+)-Coordinated Black Phosphorus Quantum Dots with Retrievable NIR/X-Ray Optoelectronic Switching Effect for Anti-Glioblastoma.

Heteroatom interaction of atomically thin nanomaterials enables the improvement of electronic transfer, band structure, and optical properties. Black phosphorus quantum dots (BP QDs) are considered to be candidate diagnostic and/or therapeutic agents due to their innate biocompatibility and exceptional photochemical effects. However, BP QDs are not competitive regarding second near-infrared (NIR-II) window medical diagnosis and X-ray induced phototherapy. Here, an Nd3+ ion coordinated BP QD (BPNd) is synthesized with the aim to sufficiently improve its performances in NIR-II fluorescence imaging and X-ray induced photodynamic therapy, benefitting from the retrievable NIR/X-ray optoelectronic switching effects between BP QD and Nd3+ ion. Given its ultrasmall size and efficient cargo loading capacity, BPNd can easily cross the blood-brain barrier to precisely monitor the growth of glioblastoma through intracranial NIR-II fluorescence imaging and impede its progression by specific X-ray induced, synergistic photodynamic chemotherapy.