Natural bioactive lysosomes extracted from multiple cells for tumor therapy

Jin Zhang; Quan Xu; Yifang Zhang; Mohamed F Foda; Kai Cai; Qing Liu; Fan Jia; Huadong Wang; Fuqiang Xu; Heyou Han; Huageng Liang

doi:10.1016/j.biomaterials.2023.122430

Natural bioactive lysosomes extracted from multiple cells for tumor therapy

Biomaterials. 2024 Jan:304:122430. doi: 10.1016/j.biomaterials.2023.122430. Epub 2023 Dec 11.

Authors

Jin Zhang¹, Quan Xu², Yifang Zhang², Mohamed F Foda³, Kai Cai², Qing Liu⁴, Fan Jia⁴, Huadong Wang⁴, Fuqiang Xu⁵, Heyou Han⁶, Huageng Liang⁷

Affiliations

¹ State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, College of Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, Shenzhen, 518055, China; State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.
² State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, College of Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
³ State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, College of Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; Department of Biochemistry, Faculty of Agriculture, Benha University, Moshtohor, Toukh, 13736, Egypt.
⁴ The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, Shenzhen, 518055, China.
⁵ The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, Shenzhen, 518055, China. Electronic address: fq.xu@siat.ac.cn.
⁶ State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, College of Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, China. Electronic address: hyhan@mail.hzau.edu.cn.
⁷ State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China; Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China. Electronic address: leonard19800318@hust.edu.cn.

PMID: 38100907
DOI: 10.1016/j.biomaterials.2023.122430

Abstract

Nanoparticles of biological origin exhibit many unique properties in biological applications due to their exquisite structure, specific composition, and natural biological functionality. In this study, we obtained lysosomes from three distinct cell types (one normal cell and two activated immune cells) and demonstrated their potential as natural therapeutic nanoparticles for tumor therapy. In vitro experiments revealed that these lysosomes maintained their structural integrity, were well-distributed, and exhibited significant biological activity, which effectively induced cancer cell death by generating ROS and disrupting biological substrates. Additionally, in vivo investigations showed that these lysosomes could accumulate in tumor tissues after intravenous administration and exhibited exceptional therapeutic effects through the destruction of tumor blood vessels and the degradation of immunosuppressive proteins, with complete tumor disappearance in a single treatment. This research on the utilization of bioactive lysosomes for tumor treatment provides valuable insights into drug development and tumor treatment, particularly when conventional approaches have proven ineffective.

Keywords: Cell-substrate degradation; Lysosomes; Nanoscale organelles; ROS generation; Tumor ablation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Death
Cell Line, Tumor
Humans
Lysosomes / metabolism
Nanoparticles* / chemistry
Neoplasms* / drug therapy
Neoplasms* / metabolism