Immunotherapy, specifically immune checkpoint inhibitors, is revolutionizing cancer treatment, achieving durable control of previously incurable or advanced tumors. However, only a certain group of patients exhibit effective responses to immunotherapy. Anti-angiogenic therapy aims to block blood vessel growth in tumors by depriving them of essential nutrients and effectively impeding their growth. Emerging evidence shows that tumor vessels exhibit structural and functional abnormalities, resulting in an immunosuppressive microenvironment and poor response to immunotherapy. Both preclinical and clinical studies have used anti-angiogenic agents to enhance the effectiveness of immunotherapy against cancer. In this review, we concentrate on the synergistic effect of anti-angiogenic and immune therapies in cancer management, dissect the direct effects and underlying mechanisms of tumor vessels on recruiting and activating immune cells, and discuss the potential of anti-angiogenic agents to improve the effectiveness of immunotherapy. Lastly, we outline challenges and opportunities for the anti-angiogenic strategy to enhance immunotherapy. Considering the increasing approval of the combination of anti-angiogenic and immune therapies in treating cancers, this comprehensive review would be timely and important.
Programmable droplet microfluidics (PDM) refers to a microfluidic device that integrates the functionality of a series of droplets with distinct spatial locations in a designated temporal order. PDM streamlines the intricate workflow of complex bioassays by enabling programmable and macroscopic droplet displacements, in which the droplets serve as reservoirs for reagents, microvalves for liquid insulation, and in some cases micropumps for mass transportation. As these droplets are intangible structures, the need for expensive microfabrication procedures is eliminated. Furthermore, the parallelization of the droplet series provides flexibility in controlling the throughput of the microfluidic analysis system. This paper provides a comprehensive review of PDMs enabled by various microfluidic mechanisms, including magnetism actuation, relative liquid displacement, capillary suction and sequential microdisplacement. Additionally, important applications of PDM systems for nucleic acid detection, immunoassay, drug testing, and sample recovery are also introduced. In conclusion, PDM demonstrates its potential as a highly advantageous tool for executing intricate multistep bioassays on a microfluidic platform. These technologies have exhibited superiority over their traditional counterparts in terms of size reduction, automation, and low sample/reagent consumption.
Light therapy techniques, such as photobiomodulation therapy (PBMT), photodynamic therapy (PDT), and laser photoablation, have gained widespread attention and become indispensable physiotherapy methods in clinical practice. PBMT involves the application of low-level laser/LED to modulate the function of nerve cells, relieve neuroinflammation, promote neurogenesis and vascular growth. Recent studies have shown that PBMT holds promise as a complementary or alternative treatment of Alzheimer’s disease (AD), traumatic brain injury (TBI), major depressive disorder (MDD), etc. However, the therapeutic effect of PBMT is influenced by various factors, such as the patients’ condition, brain structure and function, illumination parameters, etc. Therefore, the optimized parameters, personalized therapeutic schedules, and precise evaluation of the therapeutic effect are crucial to the treatment success. In this review, we identified the recent experimental and clinical successes, existing obstacles, and future opportunities for PBMT in the treatment of the brain diseases. As a non-invasive, side-effect-free, and highly accessible technique, PBMT brings a glimmer of light for the treatment of neuropsychiatric disorders and the neuro-rejuvenation of human brains.
Chimeric antigen receptor (CAR) T cells are widely used to treat hematological tumors due to their powerful ability to target and kill cancer cells, of which accurate function evaluation at the single-cell level is crucial to ensuring the efficacy of diagnosis and treatment. Currently, a universal platform to evaluate the efficacy of immune single cells rapidly, efficiently, and systematically is urgently needed. Here, the cytotoxicity, proliferative potential, and persistence of TIM3/CD28-modified CD19 CAR-T cells are evaluated in comparison with ordinary CD19 CAR-T cells through high-performance and throughput graphene oxide quantum dot (GOQD)-based single-cell microfluidic chips. Overall secretory factor expression, immune-therapy effect of different effector-target ratios, spatial immune-therapy effects, and subgroup type profiling are demonstrated to explicit the immunotherapy effect of TIM3/CD28-modified CD19 CAR-T cells. TIM3/CD28-modified CD19 CAR-T cells show stronger anti-tumor ability and maintain excellent immunotherapy effects even at low effector-target ratios and remote distances. TIM3/CD28 also strengthens the local targeting ability of TIM3/CD28-modified CD19 CAR-T. Importantly, TIM3/CD28-modified CD19 CAR-T exhibits more distinct Th1/Th2 long-term persistent and potent killer subgroups, which is very helpful for personalized therapy. Overall, this study provides a valuable approach that can be widely implemented to analyze current CAR-T combinations and evaluate the function of innovative CAR treatments in the future.
Intelligent point-of-care testing (iPOCT) is a rapidly advancing technology that combines molecular detection and bio-sensing techniques to achieve instant and accurate analysis through advanced sensors and intelligent algorithms. Molecular detection technologies, such as nucleic acid isothermal amplification, biochip and microfluidics, enable rapid analysis of the chemical composition and concentration of samples, thereby determining their presence. Bio-sensing technology utilizes the recognition properties of biomolecules in conjunction with sensors to detect specific biomolecules or biological processes. iPOCT technology holds broad prospects for application in the field of healthcare and is expected to enhance detection sensitivity, accuracy, and intelligence through further development. In this review, we delineate the developmental journey of iPOCT, followed by a discussion on the principles of molecular detection and bio-sensing technology, as well as the design of iPOCT devices for health monitoring and disease diagnosis. Furthermore, we showcased illustrative examples of iPOCT applications in disease diagnosis, highlighting the integration of iPOCT technology with wearable devices and smartphones for attaining more precise and personalized diagnostic results.
Paper-based devices have attracted considerable attention in point-of-care testing (POCT) due to their simple operation and portability. The performance of paper-based POC assays is further enhanced by coupling with functional nucleic acids (FNAs), which are able to selectively recognize and bind to targets, amplify and transduce signals. Several high-performance paper-based POC assays have been developed, resulting from the different spatial structures of the paper-based device and detection strategies using different FNAs. In this review, we first introduce FNAs and paper-based devices, including their concepts, classifications and advances. The following section focuses on the application of these FNAs in POC assays using paperbased devices, taking into account their spatial one-, two- and three-dimensional structures. Finally, the challenges and perspectives of the application of FNAs in paper-based POCT are discussed.
Non-viral vector chimeric antigen receptor (CAR)-T cells have garnered increasing attention due to their ability to efficiently eradicate cancer cells while mitigating undesirable side effects. However, the current methods for engineering chimeric antigen receptor T (CAR-T) cells employ viral vectors that result in permanent CAR expression and potentially severe negative impacts. As a solution to these challenges, triggering transitory expression of CARs in T cells via messenger RNA (mRNA) has emerged as a promising strategy. Currently, electroporation is a common method used to introduce the mRNA encoding the CAR into the T cells. Moreover, there has been increasing attention on the exploration of innovative mRNA delivery systems, including lipid, polymer-based nanoparticle, exosomes and peptide transduction domains. Additionally, we also explored the functions of different types of mRNA in mRNA-based CAR-T cell therapy. The auxiliary mRNA, exemplified by systems such as megaTAL and nuclease transposon systems, demonstrates its capacity to extend CAR-T cell viability and survival. This perspective offers the current state of mRNA-based CAR-T cell therapy and provides valuable insights into future research avenues.
With the increasing prevalence of infectious diseases caused by drug-resistant bacteria, there is an urgent need to develop innovative therapies alternative to antibiotics. Among these alternatives, the aggregation-induced emission (AIE) photosensitizers (PSs) stand out with their integrated imaging and therapeutic functionalities, allowing for early monitoring and image-guided ablation of bacteria. AIE fluorescent probes with unique optical properties excel in selective bacterial imaging. Furthermore, AIE-enabled reactive oxygen species (ROS)-mediated antibacterial photodynamic therapy can operate on multiple targets to oxidize bacteria. Also, as they are able to specifically target bacteria, AIE PSs can ameliorate the limitations of the small-scale action of ROS. This review methodically discusses the different strategies that can be employed using AIE PSs for targeting bacteria, including sheltered bacteria. The challenges and future opportunities of using AIE PSs in this emerging field are also briefly discussed.
Over the two decades, RNA drugs have gradually made their way from bench to bed. Initially, RNA was not an ideal drug since RNA molecules degrade easily and have a relatively short half-life in the circulation system. Nevertheless, the chemical modification extended the half-life of RNA in recent years, which makes RNA drugs a new star in drug discovery industry. RNA molecules hold many properties that facilitate their application as therapeutic drugs. RNAs could fold to form complex conformations to bind to proteins, small molecules, or other nucleic acids, and some even form catalytic centers. Protein-encoding RNAs are the carriers of genetic information from DNA to ribosomes, and various types of non-coding RNAs cooperate in the transcription and translation of genetic information through various mechanisms. To date, three mainstream RNA therapies have drawn widespread attention: (1) messenger RNA that encodes therapeutic proteins or vaccine antigens; (2) small interfering RNA, microRNA (miRNA), antisense oligonucleotides that inhibit the activity of pathogenic RNAs; and (3) aptamers that regulate protein activity. Here, we summarized the current research and perspectives of RNA therapies, which may provide innovative highlights for cancer therapy.
Monitoring tumor biomarkers in a non-invasive manner for tumor diagnosis has attracted increasing attention. Liquid biopsy mainly includes three types of biomarkers: circulating tumor cells, extracellular vesicles, and circulating nucleic acids. These biomarkers released by tumor cells can travel to other parts of the circulation system. The analysis of circulating tumor markers in the circulation enables early tumor diagnosis, progression evolution, and treatment monitoring, which are important for individualized clinical decisions. In this study, we summarize different DNA nanotechnology strategies that can be used to capture, amplify, and measure circulating biomarkers and discuss the current challenges and outlook.
The field of DNA nanotechnology has evolved beyond the realm of controllable movements and randomly shaped nanostructures, now encompassing a diverse array of nanomachines, each with unique nanostructures and biofunctional attributes. These DNA nanostructures boast exceptional characteristics such as programmability, integrability, biocompatibility, and universality. Among this variety, DNA walking nanomachines have emerged as one of the most prominent nanomotors, distinguished by their ingenious design and comprehensive functionality. In recent times, these DNA walkers have witnessed remarkable advancements in areas ranging from nanostructural designs to biological applications, including the creation of sophisticated biosensors capable of efficiently detecting tumor-related biomarkers and bioactive substances. This review delves into the operational mechanisms of DNA walking nanomachines, which are driven by processes such as protease and DNAzyme action as well as strand displacement and photoactivated reactions. It further provides a comprehensive overview of DNA walking nanomachines with different dimensional (1D, 2D, and 3D) walking tracks. A subsequent section introduces the biosensing applications of DNA walking nanomachines including electrochemical, optical, and other biosensors. The review concludes with a forward-looking perspective on the novel advancements and challenges in developing DNA walking nanomachine-based biosensors.