Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy
Herein, we designed a nanocarrier to deliver the LO specifically to HER2+ breast cancer (BC) cells, where functionalization of mAb (anti-HER2+) with PEGylated chitosan enabled it to target the HER2+ BC cells. Taking advantage of overexpression of HER2+ in cancer cells, our nanocarrier (CS-LO-PEG-HER...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/5/927 |
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| author | Kandasamy Saravanakumar Anbazhagan Sathiyaseelan Soyoung Park Song-Rae Kim Veeraraghavan Vishnu Priya Myeong-Hyeon Wang |
| author_facet | Kandasamy Saravanakumar Anbazhagan Sathiyaseelan Soyoung Park Song-Rae Kim Veeraraghavan Vishnu Priya Myeong-Hyeon Wang |
| author_sort | Kandasamy Saravanakumar |
| collection | DOAJ |
| description | Herein, we designed a nanocarrier to deliver the LO specifically to HER2+ breast cancer (BC) cells, where functionalization of mAb (anti-HER2+) with PEGylated chitosan enabled it to target the HER2+ BC cells. Taking advantage of overexpression of HER2+ in cancer cells, our nanocarrier (CS-LO-PEG-HER NPs) exhibited promising potency and selectivity against HER2+ BC cells (BT474). The CS-LO-PEG-HER NPs demonstrated the cytotoxicity in BT474 cells by promoting reactive oxygen species, mitochondrial membrane potential loss, and nucleus damage. The biocompatibility of CS-LO-PEG-HER NPs was evidenced by the hemolysis assay and H & E staining of major organs. The CS-LO-PEG-HER NPs showed anticancer potency against the BT474-xenograft tumor-bearing mice, as evident by the reduction of tumor size and cell density. These results indicate that CS-LO-PEG-HER NPs are biocompatible with mice while inhibiting tumor growth through alter the oxidative stress. Overall, this work provides a promising approach for the delivery of LO for good therapeutic effect in combination with mAb. |
| first_indexed | 2024-03-10T03:08:50Z |
| format | Article |
| id | doaj.art-b38e15c0cbbe4b62b6e0cdb3a535deb7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:08:50Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b38e15c0cbbe4b62b6e0cdb3a535deb72023-11-23T12:36:38ZengMDPI AGPharmaceutics1999-49232022-04-0114592710.3390/pharmaceutics14050927Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer TherapyKandasamy Saravanakumar0Anbazhagan Sathiyaseelan1Soyoung Park2Song-Rae Kim3Veeraraghavan Vishnu Priya4Myeong-Hyeon Wang5Department of Bio Health Convergence, Kangwon National University, Chuncheon 200-701, Gangwon-do, KoreaDepartment of Bio Health Convergence, Kangwon National University, Chuncheon 200-701, Gangwon-do, KoreaDepartment of Bio Health Convergence, Kangwon National University, Chuncheon 200-701, Gangwon-do, KoreaChuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Gangwon-do, KoreaDepartment of Biochemistry, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College, Saveetha University, Chennai 600077, IndiaDepartment of Bio Health Convergence, Kangwon National University, Chuncheon 200-701, Gangwon-do, KoreaHerein, we designed a nanocarrier to deliver the LO specifically to HER2+ breast cancer (BC) cells, where functionalization of mAb (anti-HER2+) with PEGylated chitosan enabled it to target the HER2+ BC cells. Taking advantage of overexpression of HER2+ in cancer cells, our nanocarrier (CS-LO-PEG-HER NPs) exhibited promising potency and selectivity against HER2+ BC cells (BT474). The CS-LO-PEG-HER NPs demonstrated the cytotoxicity in BT474 cells by promoting reactive oxygen species, mitochondrial membrane potential loss, and nucleus damage. The biocompatibility of CS-LO-PEG-HER NPs was evidenced by the hemolysis assay and H & E staining of major organs. The CS-LO-PEG-HER NPs showed anticancer potency against the BT474-xenograft tumor-bearing mice, as evident by the reduction of tumor size and cell density. These results indicate that CS-LO-PEG-HER NPs are biocompatible with mice while inhibiting tumor growth through alter the oxidative stress. Overall, this work provides a promising approach for the delivery of LO for good therapeutic effect in combination with mAb.https://www.mdpi.com/1999-4923/14/5/927L-lysine α-oxidaseHER2+trastuzumabbreast cancerPEGylated chitosan |
| spellingShingle | Kandasamy Saravanakumar Anbazhagan Sathiyaseelan Soyoung Park Song-Rae Kim Veeraraghavan Vishnu Priya Myeong-Hyeon Wang Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy Pharmaceutics L-lysine α-oxidase HER2+ trastuzumab breast cancer PEGylated chitosan |
| title | Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy |
| title_full | Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy |
| title_fullStr | Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy |
| title_full_unstemmed | Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy |
| title_short | Monoclonal Antibody Functionalized, and L-lysine α-Oxidase Loaded PEGylated-Chitosan Nanoparticle for HER2/Neu Targeted Breast Cancer Therapy |
| title_sort | monoclonal antibody functionalized and l lysine α oxidase loaded pegylated chitosan nanoparticle for her2 neu targeted breast cancer therapy |
| topic | L-lysine α-oxidase HER2+ trastuzumab breast cancer PEGylated chitosan |
| url | https://www.mdpi.com/1999-4923/14/5/927 |
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