The facultative intracellular bacterium Listeria monocytogenes (Lmo) has great potential for development as a cancer vaccine platform given its properties. However, the clinical application of Lmo has been severely restricted due to its rapid clearance, compromised immune response in tumors, and inevitable side effects such as severe systemic inflammation after intravenous administration. Herein, an immunotherapy system was developed on the basis of natural red blood cell (RBC) membranes encapsulated Lmo with selective deletion of virulence factors (Lmo@RBC). The biomimetic Lmo@RBC not only generated a low systemic inflammatory response but also enhanced the accumulation in tumors due to the long blood circulation and tumor hypoxic microenvironment favoring anaerobic Lmo colonization. After genome screening of tumors treated with intravenous PBS, Lmo, or Lmo@RBC, it was first found that Lmo@RBC induced extensive pore-forming protein gasdermin C (GSDMC)-dependent pyroptosis, which reversed immunosuppressive tumor microenvironment and promoted a systemic strong and durable anti-tumor immune response, resulting in an excellent therapeutic effect on solid tumors and tumor metastasis. Overall, Lmo@RBC, as an intravenous living bacterial therapy for the selective initiation of tumor pyrolysis, provided a proof-of-concept of live bacteria vaccine potentiating tumor immune therapy.
The development of stimuli-responsively degradable porous carriers for both controlled drug release and high biosafety is vitally important to their clinical translation, but still challenging at present. A new type of porphyrin-iron metal organic framework (Fe-MOF) nanocrystals is engineered here as acid-degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero-valence Fe atom. Fe-MOF nanocrystals exhibit excellent acid-responsive degradation for H 2 generation and simultaneous release of the loaded drug for combined hydrogen-chemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the off-target induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H 2 assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1-phenotype macrophages and consequently downregulating the expression of metastasis-related matrix metalloproteinase-2 (MMP-2) and can also downregulate the expressions of both P-glycoprotein (P-gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA. High anti-MDR/antimetastasis efficacies and high biocompatibility endow Fe-MOF nanocrystals and the Fe-MOF-based nanomedicine with high potential for clinical translation.
Gas therapy, an emerging cancer treatment method of inflammation‐related diseases, has recently received substantial attention. The rapid advances in nanomedicine and nanotechnology have made gas precision treatment possible through tumor targeted delivery and controlled release of therapeutic agents. Single therapeutic is often inevitably accompanied with limited therapy efficacy. Gas therapy combined with other treatment methods can sensitize different therapy modes to augment cancer therapy. Understanding the mechanism through which gas enhances other therapeutic modalities will enable the design of reasonable strategies for clinical cancer therapy. In this review, we summarize novel gas‐based nanomedicines, focusing on gas‐based nanomedicine carriers, along with the release of gas molecules and the mechanisms of gas enhanced therapy. We describe the design of novel gas‐releasing nanoplatforms and the underlying synergistic mechanisms against cancer. Moreover, we describe the current challenges and outlook for future prospects in novel gas‐based nanomedicines for gas therapy in cancer.
Water inrush is one of the most important risk factors in tunnel construction because of its abruptness and timeliness. Various geophysical data used in actual construction contain useful information related to groundwater development. However, the existing approaches with such data from multiple sources and sensors are generally independent and cannot integrate this information, leading to inaccurate projections. In addition, existing tunnel advanced geological forecast reports for risk projections interpreted by human operators generally contain no quantitative observations or measurements, but only consist of ambiguous and uncertain qualitative descriptions. To surmount the problems above, this paper proposes a tunnel water inrush risk analysis method by fusing multi-source geophysical observations with fuzzy identification factors. Specifically, the membership function of the fuzzy set is used to solve the difficulty in determining the basic probability assignment function in the improved Dempster–Shafer evidence theory. The prediction model of effluent conditions fuses seismic wave reflection data, ground penetrating radar data, and transient electromagnetic data. Therefore, quantitative evaluations of the effluent conditions are achieved, including the strand water, linear water, seepage and dripping water, and anhydrous. Experimental evaluations with a typical tunnel section were conducted, in which the state of the groundwater from a series of geological sketch reports in this sectionpaper were used as ground truth for verification. The experimental results revealed that the proposed method not only has high accuracy and robustness but also aligns well with different evidence effectively that generally contradicts manual interpretation reports. The results from 12 randomly selected tunnel sections also demonstrate the generalization abilities of the proposed method.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.