The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus ...on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely “1 + 1 > 2”) effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furthermore, the featured applications of multimodal synergistic therapy in overcoming tumor multidrug resistance, hypoxia, and metastasis will also be discussed in detail, which may provide new ways for the efficient regression and even elimination of drug resistant, hypoxic solid, or distant metastatic tumors. Finally, some design tips for multifunctional nanomaterials and an outlook on the future development of multimodal synergistic therapy will be provided, highlighting key scientific issues and technical challenges and requiring remediation to accelerate clinical translation.
Quantum cryptography founded on the laws of physics could revolutionize the way in which communication information is protected. Significant progresses in long-distance quantum key distribution based ...on discrete variables have led to the secure quantum communication in real-world conditions being available. However, the alternative approach implemented with continuous variables has not yet reached the secure distance beyond 100 km. Here, we overcome the previous range limitation by controlling system excess noise and report such a long distance continuous-variable quantum key distribution experiment. Our result paves the road to the large-scale secure quantum communication with continuous variables and serves as a stepping stone in the quest for quantum network.
Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue ...accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re‐activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization.
Hierarchical targeting, which combines the advantages of both enhanced tumor‐tissue accumulation/retention and enhanced cellular internalization, is a promising strategy to improve the tumor‐targeting efficiency of nanoparticles. The different strategies are summarized, including the exploitation of changeable particle sizes, switchable surface charges, and activatable surface ligands to develop hierarchical targeting nanoplatforms.
•We use the AHP-PSR model to evaluate the ecological vulnerability of Weifang City. This method uses the pressure-state-response (PSR) model to select socioeconomic and natural indicators, and uses ...the analytic hierarchy process (AHP) to determine the weights of these indicators.•The spatial autocorrelation and single parameter sensitivity of ecological vulnerability in the study area were analyzed.•This study provides reasonable advice for the ecological development of the study area.
With the continuous development of society, the contradiction between human and nature becomes increasingly prominent, and ecological vulnerability assessment is an effective tool to alleviate the contradiction. In this study, AHP-PSR (Analytic Hierarchy Process - Press-State-Response) model was used to assess the ecological vulnerability of Weifang City. PSR model was used to select parameters, AHP was used to determine the weights of parameters, and GIS was used to assess ecological vulnerability. Based on the results of ecological vulnerability assessment, the inherent ecological vulnerability assessment, single parameter sensitivity analysis and spatial autocorrelation analysis were carried out in order to provide specific suggestions for ecological development and protection in this area and provide new ideas for ecological vulnerability research. The results showed that the ecological vulnerability is from low to high, with an area of 44.1%, 44.3%, 9.7%, 0.8% and 1.1% respectively. The areas of inherent ecological vulnerability ranged from low to high are 27.2%, 38.2%, 18.0%, 6.8% and 9.8% respectively. The difference between the assessment results of ecological vulnerability and that of intrinsic ecological vulnerability, indicates the role of human society in changing the inherent natural ecological vulnerability. Human beings can improve the original highly vulnerable ecological environment through their positive activities. The single parameter sensitivity analysis supports this view. Higher and high ecological vulnerability areas should prohibit all acts that damage the ecological environment and improve the vulnerable ecological environment through positive human activities. The areas with high spatial autocorrelation mainly include the north and southeast of Shouguang County, the northeast and south of Anqiu County, Fangzi District, Hanting District, Weicheng District, Kuiwen District, Linqu County, Qingzhou County, Zhucheng County, and Gaomi County. In the case of ecological governance, priority can be given to these areas. This study can provide scientific basis for ecological construction and protection of Weifang City. Single parameter sensitivity analysis and spatial autocorrelation analysis can guide the management of ecological vulnerable areas.
Glucose oxidase (GOx) is an endogenous oxido-reductase that is widely distributed in living organisms. Over recent years, GOx has attracted increasing interest in the biomedical field due to its ...inherent biocompatibility, non-toxicity, and unique catalysis against β-d-glucose. GOx efficiently catalyzes the oxidization of glucose into gluconic acid and hydrogen peroxide (H2O2), which can be employed by various biosensors for the detection of cancer biomarkers. Various cancer therapeutic strategies have also been developed based on the catalytic chemistry of GOx: (1) the consumption of glucose provides an alternative strategy for cancer-starvation therapy; (2) the consumption of oxygen increases tumor hypoxia, which can be harnessed for hypoxia-activated therapy; (3) the generation of gluconic acid enhances the acidity of the tumor microenvironment, which can trigger pH-responsive drug release; (4) the generation of H2O2 increases the levels of tumor oxidative stress, and the H2O2 can be converted into toxic hydroxyl radicals that can kill cancer cells upon exposure to light irradiation or via the Fenton reaction. More importantly, GOx can be combined with other enzymes, hypoxia-activated prodrugs, photosensitizers or Fenton's reagents, to generate multi-modal synergistic cancer therapies based on cancer starvation therapy, hypoxia-activated therapy, oxidation therapy, photodynamic therapy, and/or photothermal therapy. Such multi-modal approaches are anticipated to exert a stronger therapeutic effect than one therapeutic mode alone. Thus, maximizing the potential of GOx in a biomedical context will offer novel clinical solutions to diagnose and treat cancer. In this tutorial review, we introduce the recent advances of GOx in cancer diagnosis and treatment. We then emphasize the design principles and biomedical applications of GOx-based biosensors and cancer therapeutic approaches. Finally, we discuss the challenges and future prospects of GOx-based catalytic systems in biomedicine.
Early diagnosis and metastasis monitoring for pancreatic cancer are extremely difficult due to a lack of sensitive liquid biopsy methods and reliable biomarkers. Herein, we developed easy-to-prepare ...and effective polydopamine-modified immunocapture substrates and an ultrathin polydopamine-encapsulated antibody-reporter-Ag(shell)-Au(core) multilayer (PEARL) Surface-Enhanced Raman Scattering (SERS) nano-tag with a quantitative signal of the Raman reporter at 1072 cm
, which achieved ultrasensitive and specific detection of pancreatic cancer-derived exosomes with a detection limit of only one exosome in 2 μL of sample solution (approximately 9 × 10
mol L
). Furthermore, by analyzing a 2 μL clinical serum sample, the migration inhibitory factor (MIF) antibody-based SERS immunoassay could not only discriminate pancreatic cancer patients (
= 71) from healthy individuals (
= 32), but also distinguish metastasized tumors from metastasis-free tumors, and Tumor Node Metastasis (TNM) P1-2 stages from the P3 stage (the discriminatory sensitivity was 95.7%). Thus, this novel immunoassay provides a powerful tool for the early diagnosis, classification and metastasis monitoring of pancreatic cancer patients.
The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, ...we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure.
Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells ...can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.
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The design and construction of polymers with diverse architectures play an important role in the field of polymer science and offers new opportunities for the development of novel ...multifunctional materials. Cyclodextrins (CDs) are attractive amphiphilic macromolecules that possess hydrophobic cavities and hydrophilic surface. The unique structures of CDs enable the design and synthesis of CD-based polymers with desired structures and functions. In this review, we systematically discuss recent advances on the design, synthesis and characterization of CD-based polymers, such as CD-cored star polymers, CD-threaded polymers and CD-capped polymers, as well as the emerging applications of CD-based polymer materials in such as self-assembled nanostructures, inorganic synthesis, intelligent hydrogels, and cancer imaging, diagnosis and therapy. The review is concluded with an overview of current challenges and perspectives.
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