Gels
·
2025
·Vol. 11
·期 3
·218
·
IF 5.3
Min Yan,Jingcui Peng,Haoan Wu,Ming Ma,Yu Zhang
Diffuse large B-cell lymphoma (DLBCL), accounting for 31% of non-Hodgkin lymphomas, remains recalcitrant to conventional therapies due to chemoresistance, metastatic progression, and immunosuppressive microenvironments. We report a novel injectable Fe 3 O 4 @DMSA@Pt@PLGA-PEG-PLGA hydrogel system integrating magnetothermal therapy (MHT), chemodynamic therapy (CDT), and immunomodulation. Under alternating magnetic fields (AMF), the system achieves rapid therapeutic hyperthermia (50 °C within 7 min) while activating pH/temperature-dual responsive peroxidase (POD) -like activity in Fe 3 O 4 @DMSA@Pt nanoparticles. Catalytic efficiency under tumor-mimetic conditions was significantly higher than Fe 3 O 4 @DMSA controls, generating elevated reactive oxygen species (ROS). Flow cytometry revealed 75.9% apoptotic cell death in A20 lymphoma cells at 50 °C, significantly surpassing CDT alone (24.5%). Importantly, this dual mechanism induced immunogenic cell death (ICD) characterized by 4.1-fold CRT externalization, 68% HMGB1 nuclear depletion, and 40.74 nM ATP secretion. This triggered robust dendritic cell maturation (92% CD86 + /CD80 + DCs comparable to LPS controls) and T cell activation (16.9% CD25 + /CD69 + ratio, 130-fold baseline). Our findings validate the therapeutic potential of magnetothermal-chemodynamic synergy for DLBCL treatment, paving the way for innovative multi-mechanism therapeutic strategies against DLBCL with potential clinical translation prospects.
研究领域:
肿瘤学
·
生物材料学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Shu-xian Liu,Jun-yu Zhang,Xiao-yan Zheng,Yong-zhong Du,Xiang-min Tong
Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent lymphomas, and can be classified as activated B-cell DLBCL (ABC-DLBCL) or germinal center B-cell DLBCL (GCB-DLBCL) according to molecular subtypes. Studies have shown that drug resistance is an important factor in its therapeutic failure. Tumor-specific drug delivery nanocarriers may be a promising strategy for the treatment of lymphoma. Herein, we developed a nanomedicine (RTX-DOX/DMF-Lip, RDDL) carrying the chemotherapeutic drugs doxorubicin (DOX) and dimethyl fumarate (DMF), and surface-modified with rituximab (RTX), which can recognize CD20 antigen when it comes into contact with the surface of a B-lymphoma cell. In the study, we found that DOX and DMF can be delivered to the tumor site precisely and demonstrate a potent synergistic anti-tumor effect. Once the nanomedicine was internalized, it induced apoptosis through ROS generation and the activation of caspase-3. Concurrently, DMF directly reduced the levels of glutathione (GSH) in tumor cells by inhibiting System Xc - , thereby resulting in impaired ROS detoxification and fostering an environment conducive to lipid peroxidation (LPO) and ferroptosis. Furthermore, the ROS generated by DOX synergistically propelled the process of ferroptosis, creating a potent therapeutic effect. These effects were validated in the GCB-DLBCL mouse model, where RDDL had a more potent killing effect compared to free drugs by striking SU-DHL-10 cells through a dual mechanism of apoptosis and ferroptosis, providing a new therapeutic strategy for the treatment of drug-resistant GCB-DLBCL.
研究领域:
肿瘤学
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-15
·
IF 3.8
Ding Yangyang,Huang Keke,Sun Cheng,Liu Zelin,Zhu Jinli,Jiao Xunyi,Liao Ya,Feng Xiangjiang,Guo Jingjing,Zhu Chunhua,Zhai Zhimin,Xiong Shudao
Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/β-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
·
癌症治疗
·
基因组学
✓ 已验证
DOI
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Qian Hu,Mengyao Wang,Meng Chen,Jinjin Wang,Ting Niu
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous subtype of non-Hodgkin lymphoma, with two-thirds of patients relapsing or resisting existing therapies, highlighting the urgent need for effective treatments. Toosendanin (TSN), a triterpenoid from Meliae Cortex, exhibits significant anti-cancer activity by modulating cell survival and proliferation. This study investigates the anti-lymphoma effects and underlying mechanisms of TSN, proposing it as a potential therapeutic agent to address the challenges of DLBCL. Network pharmacology, molecular docking, and transcriptome sequencing were employed to predict TSN's anti-DLBCL potential. Findings were validated through in vitro and in vivo experiments, including cell viability assays, flow cytometry, quantitative PCR, Western blotting, reverse experiments with small-molecule inhibitors or genetic editing, and a cell-derived xenograft (CDX) model. Bioinformatics analyses revealed TSN's strong binding affinity to PI3Kα/β and Polo-like kinase 1 (PLK1). Experiments showed that TSN downregulated the PI3K/Akt signaling pathway and reduced PLK1 mRNA and protein levels, inducing apoptosis, cell cycle arrest, and cell death in DLBCL cells. RNA sequencing and metabolic assays indicated TSN upregulated cholesterol biosynthesis in DLBCL cells. Co-treatment with a statin enhanced TSN's anti-DLBCL effects while mitigating hepatic and pulmonary toxicity. This study identifies TSN as a dual inhibitor of PI3K and PLK1 with significant therapeutic potential for DLBCL. It also proposes a lipid-modulating strategy to enhance TSN's cytotoxicity while reducing adverse effects, offering a promising approach to improve DLBCL treatment outcomes.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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