Scholarlink

Background <p>Our preliminary study found that Men1 is an oncogene and a potential therapeutic target in gastric cancer (GC). Chemotherapy remains a common therapeutic regimen for GC, but is frequently limited by multidrug resistance and poor intratumoral coordination of combination drugs. Targeting Menin may enhance chemotherapy sensitivity, but efficient co-delivery of Menin inhibitors and chemotherapeutics is hindered by the profound spatiotemporal pharmacokinetic decoupling of the drugs in vivo.</p> Methods <p>We first evaluated the synergistic antitumor effect and Menin/p53-associated mechanism of BMF-219 combined with 5-fluorouracil (5-FU) in gastric cancer models. We then engineered a hierarchically assembled, cascade-responsive hyaluronic acid (HA)-decorated liposome/mesoporous silica nanoplatform (HLM@BF) for coordinated co-delivery of BMF-219 and 5-FU. The system features a glutathione (GSH)-degradable disulfide-bridged mesoporous silica core, cloaked with a pH-sensitive lipid bilayer and decorated with HA for targeting. The synergistic efficacy and biological mechanism were evaluated through bioinformatic analysis, RNA sequencing (RNA-seq), in vitro assays, and in vivo experiments.</p> Results <p>BMF-219 sensitized GC cells to 5-FU-induced apoptosis through modulation of Menin- and p53-associated apoptotic signaling. HLM@BF was constructed successfully, and showed colloidal stability in serum-containing medium, pH/GSH-responsive co-delivery, enhanced CD44-associated uptake, endo/lysosomal redistribution or escape, increased tumor accumulation, and suppressed xenograft growth with favorable biosafety.</p> Conclusions <p>HLM@BF integrates Menin inhibition with 5-FU chemotherapy and enhances antitumor efficacy through Menin- and p53-associated apoptotic signaling, providing a targeted nanomedicine strategy for gastric cancer.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Cascade-responsive HA-decorated liposome/mesoporous silica nanoplatform co-delivering BMF-219 and 5-FU enhances gastric cancer chemotherapy through Menin- and p53-associated apoptotic signaling

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月15日

查看全文
  • Shanhu Wang,
  • Dongsheng Li,
  • Fanshuo Zeng,
  • Runchuan Wang,
  • Chhingher Ly,
  • Jinxun Jiang,
  • Zhen Wang

摘要

Background

Our preliminary study found that Men1 is an oncogene and a potential therapeutic target in gastric cancer (GC). Chemotherapy remains a common therapeutic regimen for GC, but is frequently limited by multidrug resistance and poor intratumoral coordination of combination drugs. Targeting Menin may enhance chemotherapy sensitivity, but efficient co-delivery of Menin inhibitors and chemotherapeutics is hindered by the profound spatiotemporal pharmacokinetic decoupling of the drugs in vivo.

Methods

We first evaluated the synergistic antitumor effect and Menin/p53-associated mechanism of BMF-219 combined with 5-fluorouracil (5-FU) in gastric cancer models. We then engineered a hierarchically assembled, cascade-responsive hyaluronic acid (HA)-decorated liposome/mesoporous silica nanoplatform (HLM@BF) for coordinated co-delivery of BMF-219 and 5-FU. The system features a glutathione (GSH)-degradable disulfide-bridged mesoporous silica core, cloaked with a pH-sensitive lipid bilayer and decorated with HA for targeting. The synergistic efficacy and biological mechanism were evaluated through bioinformatic analysis, RNA sequencing (RNA-seq), in vitro assays, and in vivo experiments.

Results

BMF-219 sensitized GC cells to 5-FU-induced apoptosis through modulation of Menin- and p53-associated apoptotic signaling. HLM@BF was constructed successfully, and showed colloidal stability in serum-containing medium, pH/GSH-responsive co-delivery, enhanced CD44-associated uptake, endo/lysosomal redistribution or escape, increased tumor accumulation, and suppressed xenograft growth with favorable biosafety.

Conclusions

HLM@BF integrates Menin inhibition with 5-FU chemotherapy and enhances antitumor efficacy through Menin- and p53-associated apoptotic signaling, providing a targeted nanomedicine strategy for gastric cancer.