Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.

Objective:To study the correlation between third lumbar skeletal muscle index(LSMI) and inflammatory factors and other factors in peripheral blood in gastric cancer patients.Methods:From October 2017 to December 2019, patients with gastric cancer admitted to West China Hospital Sichuan University were included. The LSMI of patients was obtained by dividing the area of skeletal muscle at the third lumbar vertebra level by the square of the height based on preoperative abdominal imaging data. The correlation between preoperative LSMI and inflammatory factors and other factors in peripheral blood were analyzed by person correlation analysis.Results:This study included 132 patients with gastric cancer. Among them, 39 were classified as stage Ⅰ, 36 were stage Ⅱ, and 57 were stage Ⅲ, respectively. Pearson correlation analysis suggested that the LSMI of gastric cancer patients was positively correlated with peripheral red blood cell count( P<0.01), hemoglobin( P<0.01), and prealbumin( P<0.01), and negatively correlated with interleukin-6(IL-6, P=0.027) and C-reactive protein(CRP, P= 0.014). Conclusion:Our study suggested that LSMI can be used as a nutritional index in gastric cancer patients and IL-6 and CRP played an important in the occurrence and development of sarcopenia in gastric cancer patients.