Citation: Xiaoyan Ma, Qiong Wu, Longfei Tan, Changhui Fu, Xiangling Ren, Qijun Du, Lufeng Chen, Xianwei Meng. Chemical chaperone delivered nanoscale metal–organic frameworks as inhibitor of endoplasmic reticulum for enhanced sensitization of thermo-chemo therapy[J]. Chinese Chemical Letters, ;2022, 33(3): 1604-1608. doi: 10.1016/j.cclet.2021.09.084 shu

Chemical chaperone delivered nanoscale metal–organic frameworks as inhibitor of endoplasmic reticulum for enhanced sensitization of thermo-chemo therapy

Xiaoyan Ma ^{a, b} ,
Qiong Wu ^{a, c} ,
Longfei Tan ^{a, c, *,} ,
Changhui Fu ^{a, c} ,
Xiangling Ren ^{a, c} ,
Qijun Du ^{a, c} ,
Lufeng Chen ^d ,
Xianwei Meng ^{a, c, *,}

a.
Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
b.
Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, Kokyo 184-8588, Japan
c.
CAS Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Beijing 100190, China
d.
First Clinical Medical School and First Hospital, Shanxi Medical University, Taiyuan 030001, China

longfeitan@mail.ipc.ac.cn

mengxw@mail.ipc.ac.cn

Received Date: 14 June 2021
Revised Date: 23 September 2021
Accepted Date: 23 September 2021
Available Online: 30 September 2021

Figures(4)

Thermotherapy and chemotherapy have received extensive attention to tumor treatment. However, thermal tolerance and drug resistance severely limit clinical effect of tumor therapy owing to endoplasmic reticulum (ER) stress. Reducing thermal tolerance and drug resistance of tumors is an urgent challenge to be solved. In this work, we design a nanoplatform of PBA-Dtxl@MIL-101 as an ER inhibitor. Amino functionalized Fe-metal organic framework (MIL-101) nanoparticles are synthesized as pH and microwave (MW) dual stimuli-responsive drug delivery system. Then, the chemical chaperones of 4-phenylbutyric acid (PBA) and antineoplastic drug Docetaxel (Dtxl) were successfully loaded into MIL-101 nanoparticles to form PBA-Dtxl@MIL-101 nanoparticles. Furthermore, PBA-Dtxl@MIL-101 nanoparticles exhibit inhibitor effect of ER stress through upregulating caspase 9 proteins and reduce thermal tolerance by downregulating HSP 90. It was demonstrated that the therapy sensitized by PBA-Dtxl@MIL-101 nanoparticles obviously destroyed tumor cells, showing simultaneously enhanced thermo-chemo therapy.
- Metal–organic frameworks,
- Biodegradable,
- Chemotherapy,
- Thermotherapy,
- Microwave
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