Selective Manipulation of the Mitochondria Oxidative Stress in Different Cells Using Intelligent Mesoporous Silica Nanoparticles to Activate On‐Demand Immunotherapy for Cancer Treatment

Author:

Chang Xiaowei1ORCID,Zhu Zeren2,Weng Lin1,Tang Xiaoyu2,Liu Tao13,Zhu Man2,Liu Jie1,Tang Wenjun2,Zhang Yanmin2,Chen Xin1ORCID

Affiliation:

1. Department of Chemical Engineering Shaanxi Key Laboratory of Energy Chemical Process Intensification Institute of Polymer Science in Chemical Engineering School of Chemical Engineering and Technology Xi'an Jiaotong University Xi'an 710049 P. R. China

2. School of Pharmacy Health Science Center Xi'an Jiaotong University Xi'an 710061 P. R. China

3. National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an 710004 P. R. China

Abstract

AbstractHerein, the vitamin K2 (VK2)/maleimide (MA) coloaded mesoporous silica nanoparticles (MSNs), functional molecules including folic acid (FA)/triphenylphosphine (TPP)/tetrapotassium hexacyanoferrate trihydrate (THT), as well as CaCO3 are explored to fabricate a core‐shell‐corona nanoparticle (VMMFTTC) for on‐demand anti‐tumor immunotherapy. After application, the tumor‐specific acidic environment first decomposed CaCO3 corona, which significantly levitates the pH value of tumor tissue to convert M2 type macrophage to the antitumor M1 type. The resulting VMMFTT would then internalize in both tumor cells and macrophages via FA‐assisted endocytosis and free endocytosis, respectively. These distinct processes generate different amount of VMMFTT in above two cells followed by 1) TPP‐induced accumulation in the mitochondria, 2) THT‐mediated effective capture of various signal ions to cut off signal transmission and further inhibit glutathione (GSH) generation, 3) ions catalyzed reactive oxygen species (ROS) production through Fenton reaction, 4) sustained release of VK2 and MA to further enhance the ROS production and GSH depletion, which caused significant apoptosis of tumor cells and additional M2‐to‐M1 macrophage polarization via different processes of oxidative stress. Moreover, the primary tumor apoptosis further matures surrounding immature dendritic cells and activates T cells to continuously promote the antitumor immunotherapy.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shaanxi Province

School of Medicine, Shanghai Jiao Tong University

Publisher

Wiley

Subject

Biomaterials,Biotechnology,General Materials Science,General Chemistry

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