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.

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.

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.

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.

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.

An Activatable Hybrid Organic-Inorganic Nanocomposite as Early Evaluation System of Therapy Effect.

Delays in evaluating cancer response to radiotherapy (RT) usually reduce therapy effect or miss the right time for treatment optimization. Hence, exploring timely and accurate methods enabling one to gain insights of RT response are highly desirable. In this study, we have developed an apoptosis enzyme (caspase-3) activated nanoprobe for early evaluation of RT efficacy. The nanoprobe bridged the nanogapped gold nanoparticles (AuNNPs) and the second near-infrared window (NIR-II) fluorescent (FL) molecules (IR-1048) through a caspase-3 specific peptide sequence (DEVD) (AuNNP@DEVD-IR1048). After X-ray irradiation, caspase-3 was activated to cut DEVD, turning on both NIR-II FL and PA imaging signals. The increased NIR-II FL/PA signals exhibited a positive correlation with the content of caspase-3. Moreover, the amount of the activated caspase-3 was negatively correlated with the tumor size. The results underscore the role of the caspase-3 activated by X-ray irradiation in bridging the imaging signals variation and tumor inhibition rate. Overall, activatable NIR-II FL/PA imaging was successfully used to timely predict and evaluate the RT efficacy. The evaluation system based on biomarker-triggered living imaging has the capacity to guide treatment decisions for numerous cancer types.

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.

NIR-II Fluorescent Biodegradable Nanoprobes for Precise Acute Kidney/Liver Injury Imaging and Therapy.

NIR-II fluorescent nanoprobes based on inorganic materials, including rare-earth-doped nanoparticles, single-walled carbon nanotubes, CdS quantum dots (QDs), gold nanoclusters, etc., have gained growing interest in bioimaging applications. However, these nanoprobes are usually not biodegradable and lack therapeutic functions. Herein, we developed novel NIR-II fluorescence (FL) imaging and therapeutic nanoprobes based on black phosphorus QDs (BPQDs), which exhibited excellent biodegradability and high tunability of size-dependent optical properties. By adjusting the size of nanoparticles, BPQDs can specifically accumulate in the kidney or liver. Importantly, a low dosage of BPQDs can effectively protect tissues from reactive oxygen species (ROS)-mediated damage in acute kidney and liver injury, which was real-time monitored by responsive NIR-II fluorescence imaging. Overall, we developed novel NIR-II emitting and therapeutic BPQDs with excellent biodegradability vivo, providing a promising candidate for NIR-II FL imaging and ROS scavenging.

NIR-II Photoacoustic Reporter for Biopsy-Free and Real-Time Assessment of Wilson's Disease.

Wilson's disease (WD) is a rare inherited disorder of copper metabolism with pathological copper hyperaccumulation in some vital organs. However, the clinical diagnosis technique of WD is complicated, aggressive, and time-consuming. In this work, a novel ratiometric photoacoustic (PA) imaging nanoprobe in the NIR-II window is developed to achieve noninvasive, rapid, and accurate Cu2+ quantitative detection in vitro and in vivo. The nanoprobe consists of Cu2+ -responsive IR970 dye and a nonresponsive palladium-coated gold nanorod (AuNR-Pd), achieving a concentration-dependent ratiometric PA970 /PA1260 signal change. The urinary Cu2+ content is detectable within minutes down to a detection limit of 76 × 10-9 m. This report acquisition time is several orders of magnitude shorter than those of existing detection approaches requiring complex procedure. Moreover, utilizing the ratiometric PA nanoprobe, PA imaging enables biopsy-free measurement of the liver Cu2+ content and visualization of the liver Cu2+ biodistribution of WD patient, which avoid the body injury during the clinical Cu2+ test using liver biopsy method. The NIR-II ratiometric PA detection method is simple and noninvasive with super precision, celerity, and simplification, which holds great promise as an alternative to liver biopsy for clinical diagnosis of WD.

Asymmetric Core-Shell Gold Nanoparticles and Controllable Assemblies for SERS Ratiometric Detection of MicroRNA.

Janus nanogap gold nanoparticles (JAuNNPs) with varying proportions of Au shell coverage of (ca. 100/75/50/25 %) are presented. The internal nanogap between the partial Au shell and core caused asymmetric optical behavior; tunability depends on the degree of Au shell coverage and structural asymmetry. The shell-to-shell or core-to-core JAuNNDs(50 %) were self-assembled from amphiphilic JAuNNPs(50 %) by tuning the hydrophilic and hydrophobic polymer brushes on the Au core or shell. The positions of electromagnetic field enhancement of JAuNNDs varied with geometrical configurations because of hybridized plasmonic coupling effects. Furthermore, DNA linkers were utilized to form JAuNND12 (50 %). By combining with Raman molecules, ratiometric SERS signals could be generated, enabling JAuNND12 (50 %) to image the distribution of miR-21 in living cells and tumors. Asymmetric JAuNNPs allowed facile conjugation of various linkage molecules to fabricate dimeric nanostructures.

Ag+ -Coupled Black Phosphorus Vesicles with Emerging NIR-II Photoacoustic Imaging Performance for Cancer Immune-Dynamic Therapy and Fast Wound Healing.

A silver-ion-coupled black phosphorus (BP) vesicle (BP Ve-Ag+ ) with a second near infrared (NIR-II) window photoacoustic (PA) imaging capability was firstly constructed to maximize the potential of BP quantum dot (QD) in deeper bioimaging and diversified therapy. The embedded Ag+ could improve the relatively large band gap of BP QD via intense charge coupling based on theoretical simulation results, subsequently leading to the enhanced optical absorption capability, accompanied with the occurrence of the strong NIR-II PA signal. Guiding by NIR-II PA bioimaging, the hidden Ag+ could be precisely released with the disassembly of Ve during photodynamic therapy process and captured by macrophages located in lesion region for arousing synergistic cancer photodynamic/Ag+ immunotherapy. BP Ve-Ag+ can contrapuntally kill pathogenic bacteria and accelerate wound healing monitored by NIR-II PA imaging.

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.

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.

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.

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.

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.

Stimuli-responsive polymer-based nanosystems for cardiovascular disease theranostics.

Stimulus-responsive polymers have found widespread use in biomedicine due to their ability to alter their own structure in response to various stimuli, including internal factors such as pH, reactive oxygen species (ROS), and enzymes, as well as external factors like light. In the context of atherosclerotic cardiovascular diseases (CVDs), stimulus-response polymers have been extensively employed for the preparation of smart nanocarriers that can deliver therapeutic and diagnostic drugs specifically to inflammatory lesions. Compared with traditional drug delivery systems, stimulus-responsive nanosystems offer higher sensitivity, greater versatility, wider applicability, and enhanced biosafety. Recent research has made significant contributions towards designing stimulus-responsive polymer nanosystems for CVDs diagnosis and treatment. This review summarizes recent advances in this field by classifying stimulus-responsive polymer nanocarriers according to different responsiveness types and describing numerous stimuli relevant to these materials. Additionally, we discuss various applications of stimulus-responsive polymer nanomaterials in CVDs theranostics. We hope that this review will provide valuable insights into optimizing the design of stimulus-response polymers for accelerating their clinical application in diagnosing and treating CVDs.

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.

Enhanced diabetic wound healing with injectable hydrogel containing self-assembling nanozymes.

To build a smart system in response to the variable microenvironment in infected diabetic wounds, a multifunctional wound dressing was constructed by co-incorporating glucose oxidase (GOx) and a pH-responsive self-assembly Cu2-xSe-BSA nanozyme into a dual-dynamic bond cross-linked hydrogel (OBG). This composite hydrogel (OBG@CG) can adhere to the wound site and respond to the acidic inflammatory environment, initiating the GOx-catalyzed generation of H2O2 and the self-assembly activated peroxidase-like property of Cu2-xSe-BSA nanozymes, resulting in significant hydroxyl radical production to attack the biofilm during the acute infection period and alleviate the high-glucose microenvironment for better wound healing. During the wound recovery phase, Cu2-xSe-BSA aggregates disassembled owing to the elevated pH, terminating catalytic reactive oxygen species generation. Simultaneously, Cu2+ released from the Cu2-xSe-BSA not only promotes the production of mature collagen but also enhances the migration and proliferation of endothelial cells. RNA-seq analysis demonstrated that OBG@CG exerted its antibacterial property by damaging the integrity of the biofilm by inducing radicals and interfering with the energy supply, along with destroying the defense system by disturbing thiol metabolism and reducing transporter activities. This work proposes an innovative glucose consumption strategy for infected diabetic wound management, which may inspire new ideas in the exploration of smart wound dressing.

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.