The hypoxia‐induced resistance to radiotherapy (RT) is a great threat to cancer patients. Therefore, overcoming the hypoxia tumor microenvironment is a vital issue. Herein, spindle‐shaped CuS@CeO2 core–shell nanoparticles combining self‐supplied oxygen, photothermal ability, and RT sensitive to cancer therapy are introduced. The spindle shape of CuS@CeO2 core–shell nanoparticles can potentiate their tumor penetration and subsequent internalization by cancer cells. The presence of CeO2, functioning as a nanoenzyme, catalyzes the endogenous H2O2 in tumor tissue into O2, which remodels the hypoxic microenvironment into one susceptible to RT. CuS nanoparticles encapsulated in CeO2 undergo a steady release and deep tumor penetration, allowing the regression of lesions less affected by RT. Furthermore, in vitro and in vivo studies reveal that the design not only mitigates the dosage of RT, but more importantly allows the entire tumor to be treated without relapses.

Background/Aims: Gastric cancer (GC) is the most common gastrointestinal malignancy, causing cancer-related deaths in East Asia. MicroRNAs (miRNAs) are small non-coding RNAs aberrantly expressed in human tumors. In this study, we aim to investigate the roles of miR-204 in the epithelial to mesenchymal transition (EMT)-associated chemosensitivity. Methods: The expression of miR-204 was detected in clinical tumor samples and GC cell lines by real time PCR. Tumor cell’s growth, invasion, and migration were measured by MTT assay, wound healing assay, and transwell invasion assay, respectively. Western blot method was used to detect the protein levels of indicated genes. Luciferase reporter assay was performed to validate the target gene of miR-204. The in vivo role of miR-204 was measured using a xenograft mouse model of GC. Results: By comparing the expressions of miR-204 in human gastric tumors and their adjacent normal tissues, it was disclosed that miR-204 was significantly downregulated in gastric tumors. Moreover, miR-204 was downregulated in multiple GC cell lines compared with normal gastric epithelial cells. Overexpression of miR-204 suppressed GC cells’ proliferation, invasion, and migration. It is noteworthy that 5-FU treatments induced miR-204 expression and suppressed TGF-β pathway. By establishment of 5-FU resistant GC cell line, it was revealed that miR-204 was significantly downregulated in 5-FU resistant GC cells, representing mesenchymal features with downregulation of epithelial marker, while mesenchymal markers were upregulated. We identified TGFBR2 as a direct target of miR-204 by Western blot method and luciferase assay in GC cells and tumor samples as well. In addition, overexpression of miR-204 sensitized GC cells to 5-FU in vitro. Xenograft experiments demonstrated that the combination of miR-204 and 5-FU efficiently inhibited tumor growth and improved survival rate of mice as well. Eventually, we illustrated the restoration of TGFBR2 in miR-204 overexpression GC cells, which recovered resistance to 5-FU treatments compared with miR-204 overexpression GC cells. Conclusion: This study describes a miRNA-based therapeutic strategy against 5-FU resistance in GC, contributing to the development of anti-chemoresistance therapeutic agents.

To ensure site–specific drug release in tumor cells and cancer-associated fibroblasts and reduce the systemic toxicity of chemotherapy, a novel drug delivery system called human serum albumin-indocyanine green-cisplatin nanoparticles was developed.

PurposeNVP-BEZ235 is a recently developed dual inhibitor of PI3K and mTOR and shows good inhibitory effects on several types of tumors. However, the efficacy of NVP-BEZ235 on gastric cancer therapy remains unclear. This study aimed to investigate the potential of NVP-BEZ235 as a new agent to enhance chemotherapy for gastric cancer.MethodsHuman gastric cancer MKN-45 cells or nude mice xenografted with MKN-45 cells were treated by NVP-BEZ235 and fluorouracil (5-FU) alone or in combination. The proliferation, invasion, apoptosis, and chemoresistance of gastric cancer cells were examined in vivo and in vitro.ResultsIn vitro, combined treatment with NVP-BEZ235 and 5-FU showed synergistic inhibitory effects on proliferation, migration, and invasion and synergistic stimulating effects on apoptosis of MKN-45 cells. In vivo, NVP-BEZ235 and 5-FU synergistically inhibited the growth and induced apoptosis of MKN-45 xenografts. Mechanistically, NVP-BEZ235 inhibited PI3K/Akt/mTOR signaling; decreased the levels of Bcl-2, MMP9, and VEGF; but increased the levels of Bax and cleaved caspase-3 in MKN-45 xenografts.ConclusionNVP-BEZ235 enhances the antitumor efficacy of 5-FU. Therefore, NVP-BEZ235 is a promising agent to enhance chemotherapy for gastric cancer.

BackgroundPhotothermal therapy (PTT) has received extensive attention owing to its non-invasive nature and highly therapeutic outcomes. PTT agents and near-infrared (NIR) laser are essential elements in PTT. However, most PTT agents are composed of heavy metals, characterized by serious cytotoxicity and side effects, and NIR irradiation often damages normal tissue owing to the high dose, thus limiting the clinical application of PTT.PurposeIn this regard, exploring new perspectives enabling more PTT agents to be enriched into the tumor and NIR laser irradiation decay in PTT is vital.MethodsIn this study, cetuximab (Ab), an anti-angiogenic antibody which targets the EGFR, was modified on CuS NPs (CuS-Ab NPs) to improve the aggregation of CuS NPs in the tumor.ResultsThe cellular uptake data and the biodistribution results showed comparable accumulation of CuS-Ab NPs in tumor, thus decreasing the cytotoxicity and side effects in normal tissues. More importantly, the modification of Ab in CuS-Ab NPs impressively inhibited the formation and progression of tumor vessels, as demonstrated by immunohistochemistry staining. The introduction of anti-vessel treatment requires CuS-Ab NPs to provide weak PTT, which means that a small amount of laser energy is required, inevitably causing negligible damage to normal tissue.ConclusionTherefore, our tailor-made CuS-Ab NPs have promising potential in clinical applications.