Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy

Thi Thuy Nguyen; Er-Yuan Chuang; Ya-Ping Chen; Po-Chun Tseng; Ming-Kai Jhan; Chun-Yi Lai; Yung-Ting Wang; Yu-Ping Hung; Chun Austin Changou; Chi-Ming Lee; Chia-Ling Chen; Chiou-Feng Lin

Biomedicine & Pharmacotherapy (Apr 2023)

Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy

Thi Thuy Nguyen,
Er-Yuan Chuang,
Ya-Ping Chen,
Po-Chun Tseng,
Ming-Kai Jhan,
Chun-Yi Lai,
Yung-Ting Wang,
Yu-Ping Hung,
Chun Austin Changou,
Chi-Ming Lee,
Chia-Ling Chen,
Chiou-Feng Lin

Affiliations

Thi Thuy Nguyen: International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Viet Nam
Er-Yuan Chuang: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; Cell Physiology and Molecular Image Research Center, Taipei Medical University-Wan Fang Hospital, Taipei 11696, Taiwan
Ya-Ping Chen: Division of Hematology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
Po-Chun Tseng: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan
Ming-Kai Jhan: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Chun-Yi Lai: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Yung-Ting Wang: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan
Yu-Ping Hung: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan
Chun Austin Changou: Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei 11031, Taiwan
Chi-Ming Lee: Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei 11031, Taiwan
Chia-Ling Chen: School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Chiou-Feng Lin: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Corresponding author at: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Journal volume & issue: Vol. 160
p. 114397

Abstract

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As an alternative strategy for cancer treatment, the combination of cancer nanomedicine and immunotherapy is promising with regard to efficacy and safety; however, precise modulation of the activation of antitumor immunity remains challenging. Therefore, the aim of the present study was to describe an intelligent nanocomposite polymer immunomodulator, drug-free polypyrrole-polyethyleneimine nanozyme (PPY-PEI NZ), which responds to the B-cell lymphoma tumor microenvironment, for precision cancer immunotherapy. Earlier engulfment of PPY-PEI NZs in an endocytosis-dependent manner resulted in rapid binding in four different types of B-cell lymphoma cells. The PPY-PEI NZ effectively suppressed B cell colony-like growth in vitro accompanied by cytotoxicity via apoptosis induction. During PPY-PEI NZ-induced cell death, mitochondrial swelling, loss of mitochondrial transmembrane potential (MTP), downregulation of antiapoptotic proteins, and caspase-dependent apoptosis were observed. Deregulated AKT and ERK signaling contributed to glycogen synthase kinase-3-regulated cell apoptosis following deregulation of Mcl-1 and MTP loss. Additionally, PPY-PEI NZs induced lysosomal membrane permeabilization while inhibiting endosomal acidification, partly protecting cells from lysosomal apoptosis. PPY-PEI NZs selectively bound and eliminated exogenous malignant B cells in a mixed culture system with healthy leukocytes ex vivo. While PPY-PEI NZs showed no cytotoxicity in wild-type mice, they provided long-term and efficient inhibition of the growth of B-cell lymphoma-driven nodules in a subcutaneous xenograft model. This study explores a potential PPY-PEI NZ-based anticancer agent against B-cell lymphoma.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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