Citation: Lin Yang, Shuaidong Zhu, Zhimei He, Xiangli Li, Jiangning Chen, Sai Bi, Jun-Jie Zhu. Aqueous-phase synthesis of upconversion metal-organic frameworks for ATP-responsive in situ imaging and targeted combinational cancer therapy[J]. Chinese Chemical Letters, ;2022, 33(1): 314-319. doi: 10.1016/j.cclet.2021.07.007 shu

Aqueous-phase synthesis of upconversion metal-organic frameworks for ATP-responsive in situ imaging and targeted combinational cancer therapy

Lin Yang ^a ,
Shuaidong Zhu ^a ,
Zhimei He ^a ,
Xiangli Li ^a ,
Jiangning Chen ^a ,
Sai Bi ^{b, *,} ,
Jun-Jie Zhu ^{a, *,}

a.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, School of Life Sciences, Nanjing University, Nanjing 210023, China
b.
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao 266071, China

bisai11@126.com

jjzhu@nju.edu.cn

Received Date: 15 May 2021
Revised Date: 1 July 2021
Accepted Date: 2 July 2021
Available Online: 11 July 2021

Figures(4)

Herein, the nanoscaled ATP-responsive upconversion metal-organic frameworks (UCMOFs) are aqueous-phase synthesized for co-delivery of therapeutic protein cytochrome c (Cyt c) and chemodrugs doxorubicin (DOX), achieving targeted combinational therapy of human cervical cancer. The UCMOFs are rationally fabricated by growing ZIF-90 on mesoporous silica-coated upconversion nanoparticles (UCNPs), in which the ZIF-90 layer attenuates the upconversion luminescence (UCL) and the rigid frameworks increase the stability of encapsulated proteins. Once the UCMOF@DOX/Cyt c are internalized into HeLa cells via specific recognition of sgc8 aptamers, the intracellular ATP triggers the dissolution of ZIF-90 into Zn²⁺, which facilitates not only the release of Cyt c and DOX but also the restoration of UCL for real-time monitoring of drug release. It has been demonstrated that the therapeutic efficacy is greatly improved by the combination of caspase-mediated apoptosis activated by Cyt c (protein therapeutics), DNA fragmentation induced by DOX (chemotherapy), and Zn²⁺-promoted generation of reactive oxygen species (ROS) (oxidative stress). Overall, our proposed multifunctional UCMOFs provide an effective platform for targeted combinational cancer therapy and in situ imaging, which hold great promise in biomedical and clinical applications.
- Upconversion nanoparticles,
- Metal-organic frameworks,
- ATP response,
- In situ imaging,
- Targeted combinational therapy
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