Photoactivated full-API nanodrug (FAND): harnessing transition metal complexes and MTH1 inhibitor for enhanced DNA damage in cancer cells

作者全名：Zhu, Huiyun; Cui, Maozhi; Tang, Qiang; Zhao, Hua; Zhang, Pu; Zeng, Shengmei; Li, Weiyu; Zhou, Qianxiong; Zhang, Jinfeng; Chen, Yongjie

作者地址：[Zhu, Huiyun; Cui, Maozhi; Tang, Qiang; Zhao, Hua; Zhang, Pu; Zeng, Shengmei; Chen, Yongjie] Chongqing Med Univ, Coll Pharm, Res Ctr Pharmacodynam Evaluat Engn Technol Chongqi, Chongqing 400016, Peoples R China; [Li, Weiyu; Zhang, Jinfeng] Beijing Inst Technol, Sch Life Sci, Beijing 100081, Peoples R China; [Zhou, Qianxiong] Chinese Acad Sci, Key Lab Photochem Convers & Optoelect Mat, Tech Inst Phys & Chem, Beijing 100190, Peoples R China

通信作者：Chen, YJ (通讯作者)，Chongqing Med Univ, Coll Pharm, Res Ctr Pharmacodynam Evaluat Engn Technol Chongqi, Chongqing 400016, Peoples R China.; Zhang, JF (通讯作者)，Beijing Inst Technol, Sch Life Sci, Beijing 100081, Peoples R China.; Zhou, QX (通讯作者)，Chinese Acad Sci, Key Lab Photochem Convers & Optoelect Mat, Tech Inst Phys & Chem, Beijing 100190, Peoples R China.

来源：BIOMATERIALS SCIENCE

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001209683300001

JCR分区：Q1

影响因子：5.8

年份：2024

卷号：12

期号：12

开始页：3154

结束页：3162

文献类型：Article

关键词：　

摘要：The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287. By virtue of its 100 wt% API content and favorable stability in water, the Ru-T FAND exhibited improved cellular uptake behavior and intracellular 1O2 generation. Attractively, the Ru-T FAND with triple anti-cancer modalities can photogenerate 1O2, photo-release DPB ligand and inhibit the repair of DNA damage, ultimately enhancing its phototherapeutic effect on cancer cells. Importantly, the uncaged DPB ligand from RuDPB emits red fluorescence, enabling real-time monitoring of the drug's absorption, distribution and efficacy. Collectively, the presented photoactivated Ru-T FANDs with multiple anti-cancer mechanisms will expand new horizons for the development of safe, efficient and synergistic tumor phototherapy strategies. The photoactivated nanodrug Ru-T FAND by self-assembly of RuDPB and TH287 was developed to achieve triple anti-cancer therapy.

基金机构：National Natural Science Foundation of China [21701018, 32371442, 22371289]; National Natural Science Foundation of China [20200125]; Science and Technology Planning Project of Yuzhong District of Chongqing City [YXY2020SDTR01]; Discipline Talent Training Program of the College of Pharmacy

基金资助正文：This research was funded by the National Natural Science Foundation of China (21701018, 32371442, 22371289), the Science and Technology Planning Project of Yuzhong District of Chongqing City (Grant No. 20200125), and the Discipline Talent Training Program of the College of Pharmacy (YXY2020SDTR01). J. Z. thanks the Biological & Medical Engineering Core Facilities (Beijing Institute of Technology) for providing advanced equipment.