Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223001853 |
| _version_ | 1797894744353800192 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Thi Thuy Nguyen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T07:14:12Z |
| format | Article |
| id | doaj.art-899855e785784d90bb16a7f6cd4b9135 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-10T07:14:12Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-899855e785784d90bb16a7f6cd4b91352023-02-26T04:26:43ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-04-01160114397Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapyThi Thuy Nguyen0Er-Yuan Chuang1Ya-Ping Chen2Po-Chun Tseng3Ming-Kai Jhan4Chun-Yi Lai5Yung-Ting Wang6Yu-Ping Hung7Chun Austin Changou8Chi-Ming Lee9Chia-Ling Chen10Chiou-Feng Lin11International 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 NamGraduate 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, TaiwanDivision of Hematology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanDepartment 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, TaiwanDepartment 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, TaiwanDepartment 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, TaiwanDepartment 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, TaiwanDepartment 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, TaiwanCore Facility Center, Office of Research and Development, Taipei Medical University, Taipei 11031, TaiwanCore Facility Center, Office of Research and Development, Taipei Medical University, Taipei 11031, TaiwanSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment 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.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.http://www.sciencedirect.com/science/article/pii/S0753332223001853PolypyrrolePolyethyleneimineNanozymeB-cell lymphomaApoptosisAnticancer |
| spellingShingle | 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 Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy Biomedicine & Pharmacotherapy Polypyrrole Polyethyleneimine Nanozyme B-cell lymphoma Apoptosis Anticancer |
| title | Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy |
| title_full | Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy |
| title_fullStr | Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy |
| title_full_unstemmed | Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy |
| title_short | Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy |
| title_sort | anticancer polypyrrole polyethylenimine drug free nanozyme for precise b cell lymphoma therapy |
| topic | Polypyrrole Polyethyleneimine Nanozyme B-cell lymphoma Apoptosis Anticancer |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223001853 |
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