One-Pot Rapid Synthesis of Cu2+-Doped GOD@MOF to Amplify the Antitumor Efficacy of Chemodynamic Therapy

Li, Qing; Yu, Jiantao; Lin, Li; Zhu, Yulin; Wei, Zixiang; Wan, Feiyan; Zhang, Xindan; He, Feng; Tian, Leilei

2023-03-01

10.1021/acsami.3c00562

ACS APPLIED MATERIALS & INTERFACES   Impact Factor & Quartile

1944-8244

1944-8252

Chemodynamic therapy (CDT) relies on the transformation of intracellular hydrogen peroxide (H2O2) to hydroxyl radicals (OH) with higher toxicity under the catalysis of Fenton/Fenton-like reagents, which amplifies the oxidative stress and induces significant cellular apoptosis. However, the CDT efficacy is generally limited by the overexpressed GSH and insufficient endogenous H2O2 in tumors. Co-delivery of Cu2+ and glucose oxidase (GOD) can lead to a Cu2+/Cu+ circulation to realize GSH depletion and amplify the Fenton-like reaction. pH-responsive metal-organic frameworks (MOFs) are the optical choice to deliver Fenton/Fenton-like ions to tumors. However, considering that the aqueous condition is requisite for GOD encapsulation, it is challenging to abundantly dope Cu2+ in ZIF-8 MOF nanoparticles in aqueous conditions due to the ease of precipitation and enlarged crystal size. In this work, a robust one-pot biomimetic mineralization method using excessive ligand precursors in aqueous conditions is developed to synthesize GOD@Cu-ZIF-8. Copper ions abundantly doped to the GOD@Cu-ZIF-8 can eliminate GSH to produce Cu+, which is further proceeded to the Fenton-like reaction in the presence of GOD-catalyzed H2O2. Through breaking the tumor microenvironment homeostasis and producing an enhanced CDT effect, the promising antitumor capability of GOD@Cu-ZIF-8 was evidenced by the experiments both in vitro and in vivo.

chemodynamic therapy metal-organic frameworks GSH depletion Fenton reaction tumor therapy

SCI

English

First ; Corresponding

National Natural Science Foundation of China[51973089] ; Shenzhen Science and Technology Innovation Commission[KQTD20170810111314625]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000959836600001

AMER CHEMICAL SOC

Web of Science

Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen 518055, Guangdong, Peoples R China

Li, Qing,Yu, Jiantao,Lin, Li,et al. One-Pot Rapid Synthesis of Cu2+-Doped GOD@MOF to Amplify the Antitumor Efficacy of Chemodynamic Therapy[J]. ACS APPLIED MATERIALS & INTERFACES,2023,15(13).

Li, Qing.,Yu, Jiantao.,Lin, Li.,Zhu, Yulin.,Wei, Zixiang.,...&Tian, Leilei.(2023).One-Pot Rapid Synthesis of Cu2+-Doped GOD@MOF to Amplify the Antitumor Efficacy of Chemodynamic Therapy.ACS APPLIED MATERIALS & INTERFACES,15(13).

Li, Qing,et al."One-Pot Rapid Synthesis of Cu2+-Doped GOD@MOF to Amplify the Antitumor Efficacy of Chemodynamic Therapy".ACS APPLIED MATERIALS & INTERFACES 15.13(2023).