The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and ...damage‐associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor‐specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual‐responsive system facilitates the nano‐prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo‐photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo‐photodynamic therapy and control‐release PTX synergistically induce gasdermin E (GSDME)‐related pyroptosis. It is speculated that inspired chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency.
A smart tumor microenvironmental reactive oxygen species/glutathione dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel and photosensitizer purpurin 18 loading is designed. Chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment the efficiency of immune checkpoint blockade therapy.
The synergistic efficacy of phototherapy and cancer immunotherapy is severely restricted by both the inherent photobleaching and aggregation‐caused quench (ACQ) defects of photosensitizers and the ...intrinsic antioxidant tumor microenvironment (TME), such as hypoxia and overexpressed glutathione (GSH). To address these issues, a novel porphyrin‐based staggered stacking covalent organic framework (COF), COF‐618‐Cu, is rationally designed as a reactive oxygen species (ROS) amplifier, owing to its excellent catalase‐like activity, COF‐618‐Cu is capable of consuming endogenous hydrogen peroxide to produce sufficient oxygen to alleviate the tumor hypoxia phenomena. Moreover the overexpressed intracellular GSH is also depleted to decrease the scavenging of ROS, due to the glutathione peroxidase mimic activity of COF‐618‐Cu. Mechanistic studies reveal that the unique staggered stacking mode between COF‐618‐Cu interlayers can effectively relieve both the photobleaching and ACQ effects that are inaccessible to commonly eclipsed COFs. These, combined with their excellent photothermal therapy performance, make COF‐618‐Cu favorable for inducing robust immunogenic cell death and remodeling TME to boost antitumor immunity.
A novel staggered stacking covalent organic framework (COF)‐based photosensitizer, COF‐618‐Cu, is reported, which can simultaneously alleviate photobleaching and aggregation‐induced quench effects to achieve desirable phototherapy performance and further elicit robust immunogenic cell death to trigger a durable antitumor immune response for boosting cancer immunotherapy.
Immune checkpoint blockade therapy is revolutionizing the traditional treatment model of multiple tumor types, but remains ineffective for a large subset of patients. Photodynamic therapy (PDT) has ...been shown to induce cancer cell death and provoke an immune response, and may represent a potential strategy to synergize with immune checkpoint blockade therapy. However, the limited tissue penetration of exciting light for conventional PDT largely hinders its application in the clinic and its further combination with immunotherapy. Here, a serrated packing covalent organic framework (COF), COF‐606, with excellent two‐photon absorption (2PA) property and photostability, largely avoids aggregation‐caused quenching, therefore offering high reactive oxygen species (ROS) generation efficiency; it is used as a 2PA photosensitizer for PDT in deep tumor tissue. COF‐606 induced PDT is shown to be efficient in inducing immunogenic cell death, provoking an immune response and normalizing the immunosuppressive status for the first time. This makes it possible to combine 2PA induced PDT using COF with programmed cell death protein 1 immune checkpoint blockade therapy. Such combination leads to strong abscopal tumor‐inhibiting efficiency and long‐lasting immune memory effects, standing as a promising combinatorial therapeutic strategy for cancer treatment.
A novel biocompatible covalent organic framework with excellent two‐photon absorption properties is used for cancer photodynamic therapy to overcome the low penetration depth of traditional photodynamic therapy. This treatment induces immunogenic cell death, alleviates immunosuppression, and further enhances the effectiveness of PD‐1‐based immunotherapy in a poorly immunogenic breast cancer mouse model.
Nanoparticle‐based tumor immunotherapy has emerged to show great potential for simultaneously regulating the immunosuppressive tumor microenvironment, reducing the unpleasant side effects, and ...activating tumor immunity. Herein, an excipient‐free glutathione/pH dual‐responsive prodrug nanoplatform is reported for immunotherapy, simply by sequentially liberating 5‐aminolevulinic acid and immunogenically inducing doxorubicin drug molecules, which can leverage the acidity and reverse tumor microenvironment. The obtained nanoplatform effectively boosts the immune system by promoting dendritic cell maturation and reducing the number of immune suppressive immune cells, which shows the enhanced adjunctive effect of anti‐programmed cell death protein 1 therapy. Overall, the prodrug‐based immunotherapy nanoplatform may offer a reliable strategy for improving synergistic antitumor efficacy.
A prodrug‐based versatile nanomedicine featured with rational size, high drug loading, and well‐controlled release is reported for enhancing cancer immunotherapy by effectively boosting the immune system by promoting dendritic cell maturation and reducing immune suppressive immune cells, producing a reliable strategy for lighting the corner of cancer immunotherapy.
A major challenge for traditional cancer therapy, including surgical resection, chemoradiotherapy, and immunotherapy, is how to induce tumor cell death and leverage the host immune system at the same ...time. Here, a myeloid‐derived suppressor cell (MDSC) membrane‐coated iron oxide magnetic nanoparticle (MNP@MDSC) to overcome this conundrum for cancer therapy is developed. In this study, MNP@MDSC demonstrates its superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, and photothermal therapy (PTT)‐induced tumor killing. Compared with red blood cell membrane‐coated nanoparticles (MNPs@RBC) or naked MNPs, MNP@MDSCs are much more effective in active tumor‐targeting, a beneficial property afforded by coating MNP with membranes from naturally occurring MDSC, thus converting the MNP into “smart” agents that like to accumulate in tumors as the source MDSCs. Once targeted to the tumor microenvironment, MNPs@MDSC can act as a PTT agents for enhanced antitumor response by inducing immunogenic cell death, reprogramming the tumor infiltrating macrophages, and reducing the tumor's metabolic activity. These benefits, in combination with the excellent biocompatibility and pharmacological kinetics characteristics, make MNP@MDSC a promising, multimodal agent for cancer theranostics.
Myeloid‐derived suppressor cell (MDSC) membranes are collected from tumor‐bearing mice and further used for magnetic Fe3O4 nanoparticle (MNP) coating. The resulting MDSC‐mimicking nanoparticles (MNP@MDSC) demonstrate superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, photothermal therapy‐induced tumor killing, and excellent biocompatibility and pharmacological kinetics characteristics. These benefits make MNP@MDSC a promising, multimodal agent for cancer theranostics.
Abstract
The signal output by the array sensor is generally very weak, with a large dynamic range and a wide range of signal frequencies. In order to solve the problem of accurate measurement of weak ...signals with wide frequency and large dynamic range, this paper proposes a design method of sub-band filtering and variable gain amplifying circuit based on the analog switch, divides the signal into four frequency bands, and designs four groups of second-order voltage control filter, and adjust the magnification for different frequency signals, and only need to switch the corresponding resistance and capacitance to realize the switching of signal processing circuits of different frequency bands, which greatly optimizes the circuit structure. In order to reduce the interference in the transmission process, a single-ended differential circuit is designed to transmit the processed signal to the subsequent acquisition system for acquisition. After the simulation test, the signal conditioning circuit can effectively improve the signal-to-noise ratio of the detection signal and improve the measurement accuracy.
Long‐term accumulation of adenosine (Ado) in tumor tissues helps to establish the immunosuppressive tumor microenvironment and to promote tumor development. Regulation of Ado metabolism is ...particularly pivotal for blocking Ado‐mediated immunosuppression. The activity of adenosine kinase (ADK) for catalyzing the phosphorylation of Ado plays an essential role in regulating Ado metabolism. Specifically, accumulated Ado in the tumor microenvironment occupies the active site of ADK, inhibiting the phosphorylation of Ado. Phosphate can protect ADK from inactivation and restore the activity of ADK. Herein, calcium phosphate‐reinforced iron‐based metal‐organic frameworks (CaP@Fe‐MOFs) are designed to reduce Ado accumulation and to inhibit Ado‐mediated immunosuppressive response in the tumor microenvironment. CaP@Fe‐MOFs are found to regulate the Ado metabolism by promoting ADK‐mediated phosphorylation and relieving the hypoxic tumor microenvironment. Moreover, CaP@Fe‐MOFs can enhance the antitumor immune response via Ado regulation, including the increase of T lymphocytes and dendritic cells and the decrease of regulatory T lymphocytes. Finally, CaP@Fe‐MOFs are used for cancer treatment in mice, alleviating the Ado‐mediated immunosuppressive response and achieving tumor suppression. This study may offer a general strategy for blocking the Ado‐mediated immunosuppression in the tumor microenvironment and further for enhancing the immunotherapy efficacy in vivo.
Calcium‐phosphate‐reinforced iron‐based metal–organic frameworks (CaP@Fe‐MOFs) are designed to reduce adenosine accumulation and to inhibit adenosine‐mediated immunosuppressive response. CaP@Fe‐MOFs regulate the adenosine metabolism by promoting adenosine‐kinase‐mediated phosphorylation and relieving the hypoxic tumor microenvironment. Moreover, CaP@Fe‐MOFs enhance the antitumor immune response via adenosine regulation, including the increase of T lymphocytes and dendritic cells and the decrease of regulatory T lymphocytes.
Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report ...that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1
and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.
A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.
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Capacity degradation monitoring of lithium batteries is necessary to ensure the reliability and safety of electric vehicles. However, capacity of cell is related to its complex internal ...physicochemical reactions and thermal effects and cannot be measured directly. A data-driven remaining capacity estimation approach for lithium-ion batteries based on charging health feature extraction is presented in this work. The proposed method utilizes rational analysis and principal component analysis to extract and optimize health features of charging stage which adapt to various working conditions of battery. The remaining capacity estimation is realized by relevance vector machine and validations of different working conditions are made with six battery data sets provided by NASA Prognostics Center of Excellence. The results show high efficiency and robustness of the proposed method.
•Health features extracted from charging voltage, current and temperature curves.•Feature optimization based on grey relational and principal component analysis.•Remaining capacity estiamtion with relevance vector machine.•Validations with battery data in various operating conditions.
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