In the process of photodynamic therapy (PDT) treatment of tumors, reactive oxygen species (ROS) plays a key role in destroying tumor tissues. However, traditional PDT often has limited ROS killing capacity due to hypoxia in the tumor microenvironment (TME) or obstruction by the ROS defense system, resulting in poor efficacy. Therefore, enhancing the killing effect of ROS on tumors is the core of enhancing the anti‐tumor effect of PDT. In recent years, many studies have developed a series of strategies to enhance the ability of ROS to kill tumors in view of the limitations of the TME on PDT. This article summarizes the commonly used or innovative strategies in recent years, including not only frequently used methods for hypoxia in the TME but also innovative strategies to inhibit the ROS defense system.
18 December 2023 in International Journal of Surgery
Background: The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors. Materials and Methods: An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and specificity of the VOCs for cancer detection. Fagan’s nomogram was designed to leverage the findings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota. Results: The pooled sensitivity, specificity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0.89, 0.88, and 0.95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the ‘ruling in’ approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the ‘ruling out’ approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identified in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in the aforementioned tumor types. Conclusions: The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These findings hold significant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets.
Glucose oxidase (GOx) can specifically catalyze the conversion of β-d-glucose into gluconic acid and hydrogen peroxide (H2O2) in the presence of oxygen, making it promising for tumor starvation therapy and oxidative therapy. However, GOx's immunogenicity, poor in vivo stability, short half-life, and potential systemic toxicity, limit its application in cancer therapy. Nanocarriers are capable of improving the pharmacological properties of therapeutic drugs (e.g. stability, circulating half-life, and tumor accumulation) and lower toxicity, hence resolving GOx issues and enhancing its efficacy. Although the application of targeted nanocarriers based on GOx has recently flourished, this field has not yet been reviewed and evaluated. Herein, we initially examined the mechanism of GOx-based nanocarriers for enhanced tumor therapy. Also, we present a comprehensive and up-to-date review that highlights GOx-based nanocarriers for tumor targeting therapy. This review expands on GOx-based nano-targeted combination therapies from both passive and active targeting perspectives, meanwhile, active targeting is further classified into ligand-mediated targeting and physical-mediated targeting. Furthermore, this review also emphasizes the present challenges and promising advancements.
1 October 2021 in International Journal of Nanomedicine
Background: Inducing the immunogenic cell death of tumour cells can mediate the occurrence of antitumour immune responses and make the therapeutic effect more significant. Therefore, the development of treatments that can induce ICD to destroy tumour cells most effectively is promising. Previously, a new type of pH-sensitive polymersome was designed for the treatment of glioblastoma which represents a promising nanoplatform for future translational research in glioblastoma therapy. In this study, the aim of this work was to analyse whether chemoradiotherapy of the novel pH-sensitive cargo-loaded polymersomes can induce ICD. Methods: Cell death in U87-MG and G422 cells was induced by [email protected], and cell death was analysed by CCK-8 and flow cytometry. The release of CRT was determined by using laser scanning confocal microscopy and flow cytometry. ELISA kits were used to detect the release of HMGB1 and ATP. The dying cancer cells treated with different treatments were cocultured with bone-marrow-derived dendritic cells (BMDCs), and then flow cytometry was used to determine the maturation rate of BMDCs (CD11c+CD86+CD80+) to analyse the in vitro immunogenicity. Tumour vaccination experiments were used to evaluate the ability of [email protected] to induce ICD in vivo. Results: We determined the optimal treatment strategy to evaluate the ability of chemotherapy combined with radiotherapy to induce ICD and dying cancer cells induced by [email protected]+RT could induce calreticulin eversion to the cell membrane, promote the release of HMGB1 and ATP, and induce the maturation of BMDCs. Using dying cancer cells induced by [email protected]+RT, we demonstrate the efficient vaccination potential of ICD in vivo. Conclusion: These results identify [email protected] as a novel immunogenic cell death inducer in vitro and in vivo that could be effectively combined with RT in cancer therapy.
1 November 2020 in International Journal of Nanomedicine
Purpose: Therapy for triple-negative breast cancer (TNBC) is a global problem due to lack of specific targets for treatment selection. Cancer stem cells (CSCs) are responsible for tumor formation and recurrence but also offer a promising target for TNBC-targeted therapy. Here, zirconium-89 (89Zr)-labelled multifunctional liposomes (MLPs) surface-decorated with chitosan (CS) were fabricated to specifically target and trace cluster of differentiation 44+ (CD44+) TNBC CSCs specifically. Patients and Methods: The biological basis of CS targeting CD44 for cancer therapy was investigated by detecting the expression of CD44 in TNBC CSCs and TNBC tissues. Molecular docking and dynamics simulations were performed to investigate the molecular basis of CS targeting CD44 for cancer therapy. Gambogic acid (GA)-loaded, 89Zr@CS-MLPs (89Zr-CS-GA-MLPs) were prepared, and their uptake and biodistribution were observed. The anti-tumor efficacy of 89Zr@CS-GA-MLPs was investigated in vivo. Results: CD44 is overexpressed in TNBC CSCs and tissues. Molecular docking and dynamics simulations showed that CS could be stably docked into the active site of CD44 in a reasonable conformation. Furthermore, 89Zr@CS-GA-MLPs were able to bind specifically to CD44+ TNBC stem-like cells and accumulated in tumors of xenograft-bearing mice with excellent radiochemical stability. 89Zr@CS-GA-MLPs loaded with GA showed remarkable anti-tumor efficacy in vivo. Conclusion: The GA-loaded, 89Zr-labelled, CS-decorated MLPs developed in this study represent a novel strategy for TNBC imaging and therapy.
16 February 2018 in International Journal of Molecular Medicine
Chemotherapy is the preferred and most common treatment for cancer in clinical practice. An increasing number of researchers all over the world are focusing on natural medicines to find new antitumor drugs, and several reports have shown that Camellia nitidissima (C. nitidissima) Chi could reduce blood-lipid, decrease blood pressure, resist oxidation, prevent carcinogenesis and inhibit tumors. Therefore, the pharmacodynamics of the chemical constituents in C. nitidissima need to be investigated further. In the present study, 16 chemical constituents were isolated from the leaves of C. nitidissima, of which 6 compounds are reported to be found in this plant for the first time. Furthermore, all these phytochemicals were screened for antitumor activity on 4 common cancer cell lines, while compound 3, one oleanane-type triterpene, exhibited the most potential antitumor effects. Interestingly, to our knowledge, this was the first report that compound 3 inhibits cancer cells. Compound 3 inhibited EGFR-mutant lung cancer cell line, NCI-H1975 via apoptosis effect, with an IC50 of 13.37±2.05 µM at 48 h. Based on the data, compound 3 showed potential for antitumor drug development, suggesting the scientific basis for the antitumor activity of C. nitidissima.