Purpose: Improving the treatment of triple-negative breast cancer (TNBC) is a serious challenge today. The primary objective of this study was to construct MUC1-C shRNA@ Fe₃O₄ magnetic nanoparticles (MNPs) and investigate their potential therapeutic benefits in alternating magnetic fields (AMF) on TNBC. Methods: Firstly, we verified the high expression of MUC1 in TNBC and synthesized specific MUC1-C shRNA plasmids (MUC1-C shRNA). Then, we prepared and characterized MUC1-C shRNA@Fe₃O₄ MNPs and confirmed their MUC1-C gene silencing effect and magneto-thermal conversion ability in AMF. Moreover, the inhibitory effects on TNBC in vitro and in vivo were observed as well as biosafety. Finally, the protein levels of BCL-2-associated X protein (Bax), cleaved-caspase3, glutathione peroxidase inhibitor 4 (GPX4), nuclear factor erythroid 2-related factor 2 (NRF2), and ferritin heavy chain 1 (FTH1) in TNBC cells and tissues were examined, and it was speculated that apoptosis and ferroptosis were involved in the synergistic treatment. Results: MUC1-C shRNA@ Fe₃O₄ MNPs have a size of ~75 nm, with an encapsulation rate of (29.78± 0.63) %, showing excellent gene therapy and magnetic hyperthermia functions. Under a constant AMF (3Kw) and a set concentration (200μg mL^{− 1}), the nanoparticles could be rapidly warmed up within 20 minutes and stabilized at about 43 °C. It could be uptaken by TNBC cells through endocytosis and significantly inhibit their proliferation and migration, with a growth inhibition rate of 79.22% for TNBC tumors. After treatment, GPX4, NRF2, and FTH1 expression levels in TNBC cells and tumor tissues were suppressed, while Bax and cleaved-caspase3 were increased. As key therapeutic measures, gene therapy, and magnetic hyperthermia have shown a synergistic effect in this treatment strategy, with a combined index (q index) of 1.23. Conclusion: In conclusion, we developed MUC1-C shRNA@Fe₃O₄ MNPs with magnetic hyperthermia and gene therapy functions, which have shown satisfactory therapeutic effects on TNBC without significant side effects. This study provides a potential option for the precision treatment of TNBC.

Breast cancer (BRCA) is the leading cause of death from malignant tumors among women. Fortunately, however, immunotherapy has recently become a prospective BRCA treatment with encouraging achievements and mild safety profiles. Since the overexpression and aberrant glycosylation of MUC1 (human mucin) are closely associated with BRCA, it has become an ideal target for BRCA immunotherapies. In this review, the structure and function of MUC1 are briefly introduced, and the main research achievements in different kinds of MUC1-mediated BRCA immunotherapy are highlighted, from the laboratory to the clinic. Afterward, the future directions of MUC1-mediated BRCA immunotherapy are predicted, addressing, for example, urgent issues in regard to how efficient immunotherapeutic strategies can be generated.

Purpose: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI). Methods: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial–mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed. Results: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras. Conclusion: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.

Ovarian cancer (OC) is a highly malignant gynecological tumor with poor current treatment effects. Telomerase reverse transcriptase (TERT) is an important component of telomerase and plays an important role in the progression of ovarian cancer. Quercetin(QR) has been shown to inhibit the cell cycle and induce the apoptosis in various types of tumors. However, the mechanism of quercetin in ovarian cancer and whether it can be applied in the treatment of ovarian cancer has not been fully understood. OC cells were intervened with QR in vitro and it was found that QR only inhibited the cell cycle but not induced cell apoptosis. By conducting network pharmacology, proteomics and TCGA-OV database analysis, we found that QR inhibited the cell cycle by binding to P53 and P21. However, in this study, overexpressed TERT in OC could bind to P53 and inhibit the binding of QR to P53, failing to induce tumor cell apoptosis. After TERT was knocked down, QR significantly suppressed the cell cycle of OC cells and induced apoptosis.To realize high drug delivery efficiency and drug targeting to improve the effect of inhibiting OC, we designed and prepared RGD-MSN/QR/shTERT nanoparticles for the combined administration of QR and shTERT. As confirmed by the in vivo experiments, RGD-MSN/QR/shTERT possessed good targeting ability and significant OC inhibiting effect, with no adverse reactions, and improved the survival benefits. This study demonstrated the mechanistic and therapeutic advantages of combining QR with shTERT in the treatment of OC. Based on this mechanism, we synthesized the novel nanoparticles (RGD-MSN/QR/shTERT) and verified the favorable OC inhibiting effect in vivo, providing a novel strategy for the treatment of OC.

Background: Discovering new and effective drugs is a top priority for treating ovarian cancer, a gynecological tumor with a high mortality rate. As a major active ingredient isolated from Paris polyphylla , Polyphyllin H exhibits antitumor effect. However, its efficacy in ovarian cancer remains unknown. This study is designed to elucidate the antitumor activity and underlying mechanism of polyphyllin H in ovarian cancer. Materials and methods: Polyphyllin H was selected from 20 traditional Chinese medicine monomers based on its high anti-proliferative activity in CCK-8 assays performed on human ovarian cancer cell lines. The effects of polyphyllin H at different concentrations on cultured ovarian cancer cells were evaluated. Polyphyllin H was administered intragastrically to the cell line-derived xenograft (CDX) mice with ovarian cancer and the tumor inhibitory effects were assessed, and the potential anti-ovarian cancer mechanisms were predicted through protein sequencing. Subsequently, the therapeutic potential was further verified in patient-derived xenograft (PDX) mouse model. Results: The in vitro experiments demonstrated that polyphyllin H potently inhibited the proliferation, invasion, and migration of ovarian cancer cells while promoting cellular apoptosis. In vivo studies further confirmed that polyphyllin H significantly suppressed ovarian tumor growth, without inducing hepatic, renal and hematopoietic dysfunction, intestinal flora disturbance and major visceral histopathological change. Mechanistically, polyphyllin H upregulated cingulin (CGN) expression, blocking the RhoA/Rock2 signaling pathway to inhibit ovarian cancer malignant progression. Notably, polyphyllin H exerted promising antitumor efficacy in ovarian cancer PDX model, particularly demonstrating superior therapeutic effects against Her2-positive ovarian cancer. Conclusion: This study demonstrates that polyphyllin H inhibits the malignant progression of ovarian cancer via the CGN/RhoA/Rock2 pathway, without notable toxic and side effects. It provides a novel candidate drug for ovarian cancer therapy. Notably, the efficacy of polyphyllin H in ovarian cancer PDX models indicates its translational potential for clinical application.

Lung squamous cell carcinoma (LUSC) is a common type of non-small-cell lung cancer with high mortality, lacks effective diagnostic indicators and therapeutic targets. This study aims to reveal that low expression of Alpha-Sarcoglycan (SGCA) promotes LUSC progression and to provide a biomarker for its diagnosis, prognosis evaluation, and targeted therapy. TCGA data and 70 clinical LUSC patients were analyzed. In vitro, H520 and H1703 cells with overexpressed SGCA were transfected with pc-SGCA plasmids, and their proliferation, apoptosis, and invasion were examined. In vivo, a subcutaneous tumorigenic mouse model was constructed. SGCA was significant in diagnosing LUSC and negatively correlated with T stage. Low SGCA expression enhanced proliferation, invasion, and migration, and inhibited apoptosis. Overexpression of SGCA inhibited tumor growth in mice. Low expression of SGCA is closely associated with LUSC progression, making it a potential prognostic factor and therapeutic target for LUSC.