Multifunctional ZnO@DOX/ICG-LMHP Nanoparticles for Synergistic Multimodal Antitumor Activity

Zhuoyue Li; Jingru Wang; Junwei Liu; Jianming Yu; Jingwen Wang; Hui Wang; Qingchao Wei; Man Liu; Meiqi Xu; Zhenhan Feng; Ting Zhong; Xuan Zhang

doi:10.3390/jfb15020035

Multifunctional ZnO@DOX/ICG-LMHP Nanoparticles for Synergistic Multimodal Antitumor Activity

J Funct Biomater. 2024 Jan 30;15(2):35. doi: 10.3390/jfb15020035.

Authors

Zhuoyue Li^{1

2}, Jingru Wang^{1

2}, Junwei Liu^{1

2}, Jianming Yu^{1

2}, Jingwen Wang^{1

2}, Hui Wang^{1

2}, Qingchao Wei^{1

2}, Man Liu^{1

2}, Meiqi Xu^{1

2}, Zhenhan Feng^{1

2}, Ting Zhong^{1

2}, Xuan Zhang^{1

2}

Affiliations

¹ Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
² Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Abstract

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn²⁺ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O₂) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.

Keywords: doxorubicin; indocyanine green; multifunctional nanoparticles; multimodal antitumor activity; zinc oxide.

Grants and funding

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (No. 81773646), the National Key Research and Development Program of China (2017YFA0205600) and the Innovation Team of the Ministry of Education (No. BMU2017TD003).