Fan Ying,Gao Ruihan,Jiang Yangming,Bian Bing,Tao Zhu,Wei Gang,Xiao Xin
In this work, we report a conceptual strategy for preventing pesticide degradation using cucurbit[n]uril to encapsulate pyroquilon (Pyn). The host–guest inclusion complexes of pyroquilon (Pyn) with CB[7] and CB[8] were prepared and characterized using 1 H NMR spectroscopy, quadrupole-time of flight mass spectrometry (Q-TOF), isothermal titration calorimetry (ITC) and UV absorbance spectrophotometry. The experimental results revealed that the entire Pyn molecule resides within the cavities of CB[7] and CB[8], forming 1:1 inclusion complexes between CB[n] and Pyn. Our study on the release of Pyn demonstrated that CB[n]@Pyn exhibit sustained- and slow-release properties. Moreover, CB[8] can effectively shield UV irradiation and thereby protect the Pyn from photodegradation. Therefore, CB[7]@Pyn and CB[8]@Pyn have great potential to be used as slow-release agents.
Chemotherapy with spatiotemporal precision and noninvasiveness offers a new treatment strategy for colorectal cancer. However, this therapy still has shortcomings in how chemotherapeutic drugs are visualized and their antitumor effects. To improve the therapeutic efficacy, we have fabricated a facile host–guest complex (OTC) that resorts to noncovalent interactions among oxaliplatin (OxPt), photosensitizer (TTVP), and cucurbit[8]uril (CB[8]). OTC significantly enhanced the aggregation-induced emission (AIE) effect of TTVP. We further confirmed that OTC targeted aggregation in tumors by xenograft nude mouse models. This enabled the functions of tracing the chemotherapeutic drug, localizing the tumor, and targeting tumor accumulation. The tumor growth inhibition value (TGI) was 68.01% in the OTC group. Importantly, OTC-regulated drug release was observed through spermidine exchange in vitro and in vivo. The toxicity of OTC to normal cells under light-avoidance conditions was significantly less than that of conventional chemotherapeutic agents (OxPt), implying that OTC exhibited high efficacy and low toxicity. Upon light irradiation, OTC generated reactive oxygen species (ROS), leading to oxidative damage, while MDA levels were elevated, but SOD and CAT activities were reduced. We found that HMGB1, CRT, and ATP in the OTC-treated group increased by 87.20, 43.30, and 34.60% in vitro, respectively, compared with the control group. Transcriptomic analysis revealed upregulation of pathways related to immune activation, suggesting that OTC treatment primed the tumor for immunotherapy. The possible biological mechanism behind this was that OTC activated oxidative damage to induce immunogenic cell death (ICD). Overall, OTC offers a simple, visual, and highly efficient method for transporting platinum to improve chemotherapy. It also provides a novel strategy for combining chemotherapy and immunotherapy in solid tumors.
Liangliang Xiang,Wenting Cheng,Jiakang Zhang,Xiaoyue Li,Adeel Khan,Yongxiang Yi,Jinlong Li
Matrix metalloproteinase-9 (MMP-9) has been implicated in various tumor cell invasions and metastases. In light of the limitations of traditional methods for MMP-9 detection, we have constructed a novel biosensor depending on cucurbit[8]uril (CB[8]) -mediated host-guest interactions and a sacrificial iron metal-organic framework (FeMOF). Herein, MMP9-specific peptides modified on the gold bare electrode are bonded to the [email protected] @peptide complex through CB[8] addition. The connection between MMP9-specific peptides and signal peptides via CB[8] provides stability as well as enables the immobilization of FeMOF on the electrode surface . When Fe 3+ from the FeMOF interacts with electrochemical buffer K 4 Fe(CN) 6 , Prussian blue will be generated on the gold electrode surface, and a significantly enlarged current response can be detected. However, in the presence of MMP-9, their peptide substrates are specifically cleaved at the site between serine (S) and Leucine (L), which causes an abrupt decrease in the electrochemical signal. The change of signal can reflect MMP-9 concentration. This sensor can reach an ultrahigh sensitivity with a wide detection range of 0.5 pg⋅mL −1 to 500 ng⋅mL −1 and a low detection limit of 1.30 pg⋅mL −1 . Importantly, this sensor is very simple, relying solely on self-sacrificial label of FeMOF, rather than complex functional materials. Additionally, it has been well used in serum samples, showing attractive potential for practical applications.
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