Synergistic Regulation of Targeted Organelles in Tumor Cells to Promote Photothermal-Immunotherapy Using Intelligent Core-Satellite-Like Nanoparticles for Effective Treatment of Breast Cancer.
Xiaowei ChangXiaoyu TangWenjun TangLin WengTao LiuZeren ZhuJie LiuMan ZhuYanmin ZhangXin ChenPublished in: Small (Weinheim an der Bergstrasse, Germany) (2024)
The normal operation of organelles is critical for tumor growth and metastasis. Herein, an intelligent nanoplatform (BMA EF ) is fabricated to perform on-demand destruction of mitochondria and golgi apparatus, which also generates the enhanced photothermal-immunotherapy, resulting in the effective inhibition of primary and metastasis tumor. The BMA EF has a core of mesoporous silica nanoparticles loaded with brefeldin A (BM), which is connected to ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and folic acid co-modified gold nanoparticles (A EF ). During therapy, the BMA EF first accumulates in tumor cells via folic acid-induced targeting. Subsequently, the schiff base/ester bond cleaves in lysosome to release brefeldin A and A EF with exposed EGTA. The EGTA further captures Ca 2+ to block ion transfer among mitochondria, endoplasmic reticulum, and golgi apparatus, which not only induced dysfunction of mitochondria and golgi apparatus assisted by brefeldin A to suppress both energy and material metabolism against tumor growth and metastasis, but causes A EF aggregation for tumor-specific photothermal therapy and photothermal assisted immunotherapy. Moreover, the dysfunction of these organelles also stops the production of BMI1 and heat shock protein 70 to further enhance the metastasis inhibition and photothermal therapy, which meanwhile triggers the escape of cytochrome C to cytoplasm, leading to additional apoptosis of tumor cells.
Keyphrases
- endoplasmic reticulum
- cancer therapy
- drug delivery
- photodynamic therapy
- heat shock protein
- gold nanoparticles
- oxidative stress
- cell death
- drug release
- high glucose
- diabetic rats
- stem cells
- reactive oxygen species
- body mass index
- cell proliferation
- physical activity
- mesenchymal stem cells
- cell therapy
- walled carbon nanotubes