首页|Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy

Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy

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Chemotherapy is the first-line treatment for cancer,but its systemic toxicity can be severe.Tumor-selective prodrug activation offers promising opportunities to reduce systemic toxicity.Here,we present a strategy for activating prodrugs using radiopharmaceuticals.This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals.[18F]FDG(2-[18F]-fluoro-2-deoxy-D-glucose),one of the most widely used radiopharmaceuticals in clinics,can trig-ger Pt(Ⅳ)complex for controlled release of axial ligands in tumors,it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide 18F.Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice.Of note,an OxaliPt(Ⅳ)linker is designed to construct an[18F]FDG-activated antibody-drug conjugate(Pt-ADC).Sequential injection of Pt-ADC and[18F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth.Radiotherapy is booming as a perturbing tool for prodrug activation,and we find that[18F]FDG is capable of deprotecting various radiotherapy-removable protecting groups(RPGs).Our results suggest that tumor-selective radiopharmaceutical may function as a trigger,for devel-oping innovative prodrug activation strategies with enhanced tumor selectivity.

Prodrug activationRadiopharmaceuticalRadiochemistry[18F]FDGPlatinum(Ⅳ)prodrug

Changlun Wang、Mengxin Xu、Zihang Zhang、Senhai Zeng、Siyong Shen、Zexuan Ding、Junyi Chen、Xi-Yang Cui、Zhibo Liu

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Beijing National Laboratory for Molecular Sciences,Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science,Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,College of Chemistry and Molecular Engineering,Peking University,Beijing 100871,China

Changping Laboratory,Beijing 102206,China

Peking University-Tsinghua University Center for Life Sciences,Peking University,Beijing 100871,China

Key Laboratory of Carcinogenesis and Translational Research of M

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Beijing Municipal Natural Science FoundationNational Natural Science Foundation of ChinaMinistry of Science and Technology of the People's Republic of ChinaProgram of the Local Science and Technology Development(Gansu Province)Guided by Central GovernmentChangping LaboratoryCentral Guidance for Local Science and Technology Development ProjectsAnalytical Instrumentation Center of Peking University

Z200018222256032021YFA1601400YDZX20216200001201202138-03

2024

10.1016/j.scib.2024.07.010

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(17)