In this work, we reported a novel and effective cancer treatment strategy by fabricating carbon dot (CD)-polyethylenimine (PEI)-doxorubicin (DOX) antitumor drug complexes from a combination of PEI-passivated CDs (CD-PEI) and DOX. CD-PEI was synthesized by the one-step microwave hydrothermal carbonization of a mixture of glycerol and PEI-25k, enabling simultaneous synthesis and surface passivation of CDs. DOX was loaded onto CD-PEI by electrostatic interactions. The results show that this system not only improves selective drug release but also prolongs the drug release time and improves the killing effect on tumors. Compared with free DOX, the CD-PEI-DOX complex has a stronger killing effect on liver cancer cells (MHCC-97L and Hep3B cells) but a very low killing effect on normal liver cells (L02). Studies have also confirmed that compared with DOX alone, CD-PEI-DOX nanoparticles can effectively inhibit tumors because of the larger amount of drugs localized in tumor cells and the higher apoptosis rate of MHCC-97L cells. In vivo experiments confirmed that CD-PEI-DOX has a stronger inhibitory effect on tumor growth, indicating that CD-PEI-DOX nanomedicine has inhibitory effects on tumors.

Background: Nanomaterials exhibited intrinsic enzyme-like properties due to the unique properties compared with natural enzyme. Carbon dots (CDs) are an important kind of quantum-sized nanomaterials, which have enormous application potential in bio-imaging, drug carrier, and nanosystems. Carbon dots possess intrinsic enzyme-like properties, such as glutathione (GSH) oxidase or peroxidase activities. Methods: A co-delivery nanosystem that could carry siRNA and doxorubucin (DOX) simultaneously has been studied in this work. The co-delivery based on carbon dots was surface-modified with poly-ethylenimine (PEI) and loaded the siMRP1 with chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI was raw materials and passivator during the reaction process that makes CDs exhibit excellent optical property. Results: The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumors and releasing them synchronously in cells in an acid-triggered manner. The particles exhibited GSH oxidase-like catalytic property, oxidizing GSH to oxidized glutathione with concomitant increase of reactive oxygen species (ROS). We found that silencing of MRP1 by co-delivery system antagonized chemoresistance by increasing DOX accumulation and significantly enhancing the inhibitory effect of cell viability induced by CD-PEI-DOX. The co-delivery system dramatically inhibited tumor growth in xenograft model, and CDs counteracted MRP1 function by siRNA-mediated knockdown of MRP1. Conclusion: Taken together, we uncover the potential role of CDs with a combination of siRNA and chemotherapeutics in overcoming chemoresistance of lung cancer by suppressing MRP1 and oxidation of GSH. Our findings imply its potential of antagonizing chemoresistance to enhance therapeutic efficiency of doxorubicin in clinical practices of lung cancer treatment.

Sulfiredoxin 1 (SRXN1) is a pivotal regulator of the antioxidant response in eukaryotic cells. However, the role of SRXN1 in hepatocellular carcinoma (HCC) is far from clear. The present study aims to elucidate whether SRXN1 participates in tumorigenesis and metastasis of HCC and to determine the molecular mechanisms. We found that SRXN1 expression was up‐regulated in HCC tissue samples and correlated with poor prognosis in HCC patients. We also observed that SRXN1 knockdown by transient siRNA transfection inhibited HCC cell proliferation, migration and invasion. Overexpression of SRXN1 increased HCC cell migration and invasion. B‐cell translocation gene 2 (BTG2) was identified as a downstream target of SRXN1. Mechanistic studies revealed that SRXN1‐depleted reactive oxygen species (ROS) modulated migration and invasion of HCC cells. In addition, the ROS/p65/BTG2 signalling hub was found to regulate the epithelial‐mesenchymal transition (EMT), which mediates the pro‐metastasis role of SRXN1 in HCC cells. In vivo experiments showed SRXN1 promotes HCC tumour growth and metastasis in mouse subcutaneous xenograft and metastasis models. Collectively, our results revealed a novel pro‐tumorigenic and pro‐metastatic function of SRXN1 in HCC. These findings demonstrate a rationale to exploit SRXN1 as a therapeutic target effectively preventing metastasis of HCC.

A major characteristic of ovarian cancer (OC) is its unique route of metastasis via ascites. The immune microenvironment in ascites remains understudied, leaving the mechanism of ascites‐mediated abdominal metastasis obscure. Here, a single‐cell transcriptomic landscape of CD45⁺ immune cells across multiple anatomical sites is depicted, including primary tumors, metastatic lesions, and ascites, from patients diagnosed with high‐grade serous ovarian carcinoma (HGSOC). A novel subset of perilipin 2 high (PLIN2^hi) macrophages are identified that are enriched in ascites and positively correlated with OC progression, hence being designated as “ascites‐associated macrophages (AAMs)”. AAMs are lipid‐loaded with overexpression of the lipid droplet protein PLIN2. Overexpression or suppression of PLIN2 can enhance or inhibit tumor cell migration, invasion, and vascular permeability in vitro, which is also confirmed in vivo. Mechanistically, it is demonstrated that PLIN2 boosts HIF1α/SPP1 signaling in macrophages, thereby exerting pro‐tumor functions. Finally, a PLIN2‐targeting liposome is designed to efficiently suppress ascites production and tumor metastasis. Taken together, this work provides a comprehensive characterization of the cancer‐promoting function and lipid‐rich property of ascites‐enriched PLIN2^hi macrophages, establishes a link between lipid metabolism and hypoxia within the context of the ascites microenvironment, and elucidates the pivotal role of ascites in trans‐coelomic metastasis of OC.

Background: To investigate the effect of mannose on radio-sensitivity of human esophageal squamous cell carcinoma (ESCC) cell line and its possible mechanism. Methods: The expression of mannose phosphate isomerase (MPI) in human esophageal cancer cell lines were detected by Western blot. The inhibitory effect of mannose on human esophageal cancer cell lines were observed by MTT assay. Plate clone formation assay was performed to investigate the efficacy of mannose on radio-sensitivity of human esophageal cancer cells. The apoptosis rates of tumor cells treated with mannose and/or radiation therapy was calculated by flow cytometry. Furthermore, we analyzed intracellular metabolites using liquid chromatography mass spectrometry to identify selective sugar metabolites. Results: MPI expression was various in human esophageal cancer cells. KYSE70 cells was associated with the highest MPI expression whereas KYSE450 cells had the lowest MPI expression level. When administrated with 11.1 mM/L mannose, the same inhibitory effect was observed in both KYSE70 and KYSE450 cell lines. Moreover, the inhibitory effect was significant on KYSE450 cell lines with an increased mannose concentration. The application of 11.1 mM/L mannose could significantly enhance the radio-sensitivity of KYSE450 cell line; and tumor cell apoptosis rate was also increased. However, there was limited efficacy of mannose on the radio-sensitivity and apoptosis rate of KYSE70 cell line. Additionally, intracellular metabolites analyzation revealed that glycolysis could be disturbed by mannose when combined with radiation therapy in esophageal cancer cells. Conclusion: In esophageal cancer cell lines with low MPI expression, the administration of mannose was associated with enhanced radio-sensitivity.

Previous studies have shown that selenium possessed chemotherapeutic effect against multiple malignant cancers, inducing diverse stress responses including apoptosis and autophagy. Selenite was previously shown to induce apoptosis and autophagy in colorectal cancer cells. However, the relationship between selenite-induced apoptosis and autophagy was not fully understood. Our results revealed a pro-survival role of selenite-induced autophagy against apoptosis in colorectal cancer cells. Real-time PCR array of autophagy-related genes showed that GABARAPL-1 was significantly upregulated in colorectal cancer cells, which was confirmed by western blot and immunofluorescence results. Knockdown of GABARAPL-1 significantly inhibited selenite-induced autophagy and enhanced apoptosis. Furthermore, we found that selenite-induced upregulation of GABARAPL-1 was caused by upregulated p-AMPK and FoxO3a level. Their interaction was correlated with involved in regulation of GABARAPL-1. We observed that activation and inhibition of AMPK influenced both autophagy and apoptosis level via FoxO3a/ GABARAPL-1 signaling, implying the pro-survival role of autophagy against apoptosis. Importantly, we corroborated these findings in a colorectal cancer xenograft animal model with immunohistochemistry and western blot results. Collectively, these results show that sodium selenite could induce ROS/AMPK/FoxO3a/GABARAPL-1-mediated autophagy and downregulate apoptosis in both colorectal cancer cells and colon xenograft model. These findings help to explore sodium selenite as a potential anti-cancer drug in clinical practices.