肿瘤治疗,华西医院 z-bio 2025-07-10 3756

　　Recently, West China Hospital of Sichuan University has made breakthrough progress in the field of innovative tumor treatment, and has published two important research results in top academic journals, demonstrating its strong strength in the research direction of cross-fusion of tumor nanomedicine and immunotherapy.

　　These two studies focus on the treatment bottlenecks of refractory triple-negative breast cancer (TNBC) and immune "cold tumors". Through exquisite nano-drug design, they propose promising new strategies for collaborative treatment, providing new ideas and new platforms for solving key clinical problems.

　　Article 1

　　Prodrug-based combined nanodrugs enhance ferrous death and immune activation by remodeling lipid metabolism

　　Triple-negative breast cancer (TNBC) is a breast cancer subtype with high malignancy and poor prognosis. Due to the lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), it is not sensitive to endocrine therapy and targeted therapy. It mainly relies on chemotherapy in clinical practice, but it is prone to drug resistance and recurrence, and the treatment effect is limited. New treatment strategies are urgently needed.

　　As a programmed cell death model characterized by lipid peroxidation imbalance, ferrodystrophy has been closely related to tumor occurrence and development in recent years, especially in refractory tumors.

　　By enhancing ferrodysfunction, the induction of tumor cell death may break through the limitations of traditional treatment. At the same time, nanodrug delivery systems have become an important research direction for tumor treatment because they can improve drug targeting, reduce toxic and side effects, and can realize co-delivery of multiple drugs to exert synergistic effects.

　　Based on this, on May 15, 2025, Professor Jing Jing's team from West China Hospital of Sichuan University published an article titled "Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immunoactivation" in Acta Pharmaceutica Sinica B (IF=14.6). The study combined chemotherapy, phototherapy and ferroptosis regulation mechanisms to design a combined nanodrug with heparin as a carrier, aiming to achieve more efficient anti-tumor effects by destroying TNBC cells' lipid metabolism, enhancing ferroptosis and activate immune responses, and provide new ideas and platforms for TNBC treatment.

　　The study focused on the treatment of triple-negative breast cancer (TNBC), and based on the anti-tumor potential of ferrodystrophy, a bimodal nanopharmaceutical (HH-PP). The drug is formed by grafting poly(N-(2'-hydroxy)propylmethacrylamide) (pHP) by heparin (HP) and is combined with paclitaxel (chemotherapeutic drug) and pyrodemagnesium chlorochloric acid-a (phototherapeutic drug).

　　Experimental results show that HH-PP can destroy lipid metabolism and induce lipid oxidative imbalance in TNBC cells, thereby enhancing ferrous death; it can significantly inhibit tumor growth in the body (inhibition rate 86.63%) and activate adaptive immunity (increase CD8 + cytotoxic T cell infiltration).

　　This study provides a new platform for co-delivery of multiple drugs, confirming that it can achieve effective treatment of TNBC by enhancing ferrodystrophy and related immune activation.

　　Article 2

　　Tumor targeted nanocarriers: Activating STING and inhibiting immune escape to enhance cold tumor immunotherapy

　　Low immunogenicity and immune escape are the main bottlenecks in tumor immunotherapy.

　　On June 27, 2025, Professor Mi Peng from West China Hospital of Sichuan University, as an independent corresponding author, published a research paper titled "Tumor-targeting nanocarriers amplified immunotherapy of cold tumors by STING activation and inhibiting immunoeval", focusing on the core issues of poor tumor immunotherapy caused by low immunogenicity ("cold tumor") and immune escape.

　　Previous studies have shown that only a few tumors in immunotherapy are sensitive to immune checkpoint inhibitors, and the key reason is the tumor heterogeneity and low immunogenic tumor microenvironment. The STING pathway is crucial in activates anti-tumor immunity. After being activated by an agonist, it can induce cytokines such as type I interferon, promote the maturation of antigen-presenting cells and cytotoxic T cell responses, etc. However, the existing interferon gene stimulating factor (STING) agonists have problems such as easy degradation and low delivery efficiency, which limits the efficacy.

　　Here, the researchers synthesized a multifunctional polymer containing photosensitizers, cations and thiol derivatives, and constructed a nanocarrier (cGAMP-siPDL1@GalNPs) loaded with galactose-modified STING agonist and programmed death ligand 1 (PD-L1) small interfering RNA (siPDL1), aiming to achieve synergistic immunotherapy for low-immunogenic tumors by stimulating a strong immune response.

　　This nanocarrier can efficiently deliver drugs to cancer cells by targeting galactose receptors, triggering the release of luminescence/redox/pH-activated drugs, which not only stimulates anti-tumor immunity through activation of STING and induction of immunogenic cell death (ICD), but also inhibits immune escape by knocking down PD-L1 expression, and synergistically improves the immunosuppressive tumor microenvironment.

　　To sum up, these two studies at West China Hospital not only show the precise regulation potential of nano drugs in tumor treatment, but also reveal a new mechanism of synergistic interaction between metabolic intervention and immune activation.

　　In the future, with the acceleration of optimization and iteration of nanocarriers and clinical transformation, this type of multimodal therapy strategy is expected to further integrate radiotherapy, gene editing and other means to form a more efficient "immune-metabolism-physics" combination therapy. West China Hospital's continued deepening in the field of tumor immunity not only provides a paradigm for basic research, but also brings new hope for clinical individualized treatment, marking that my country has entered the international forefront in the field of precise tumor treatment.