A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro

Osteosarcoma is an aggressive malignant neoplasm, and it is of great significance to the fabrication and investigation of the anti-tumor mechanism of nanomedicine in the treatment of osteosarcoma. Herein, a cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-&l...

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Main Authors: Jiapeng Deng, Qichang Wang, Huihui Xu, Guoqing Li, Su Liu, Yixiao Chen, Fei Yu, Weiqiang Yan, Hui Zeng, Peng Liu
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/6/1524
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author Jiapeng Deng
Qichang Wang
Huihui Xu
Guoqing Li
Su Liu
Yixiao Chen
Fei Yu
Weiqiang Yan
Hui Zeng
Peng Liu
author_facet Jiapeng Deng
Qichang Wang
Huihui Xu
Guoqing Li
Su Liu
Yixiao Chen
Fei Yu
Weiqiang Yan
Hui Zeng
Peng Liu
author_sort Jiapeng Deng
collection DOAJ
description Osteosarcoma is an aggressive malignant neoplasm, and it is of great significance to the fabrication and investigation of the anti-tumor mechanism of nanomedicine in the treatment of osteosarcoma. Herein, a cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-<i>b</i>-P(C7-<i>co</i>-CA)) was fabricated, and the anti-osteosarcoma mechanism of mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelle was investigated. mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles were prepared by self-assembly method, and their diameter was 227 nm. mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles could regulate the cell cycle and inhibit the proliferation of 143B cells, which was demonstrated by flow cytometry analysis, CCK-8 assay and 5-Ethynyl-2′-deoxyuridine (EdU) staining. The wound-healing assay and transwell assay showed that mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles effectively inhibited the migration and invasion of 143B cells. It was proven that mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles downregulated the levels of proliferation and apoptosis-related proteins and affected osteosarcoma migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). In addition, mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles can also inhibit the transcriptional activity of the PI3K/Akt signaling pathway. Therefore, these findings provide new evidence for the pharmacological effects of mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles.
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spelling doaj.art-ee0c2dcf996841628e1dbf37f7c4843d2023-11-18T09:24:34ZengMDPI AGBiomedicines2227-90592023-05-01116152410.3390/biomedicines11061524A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In VitroJiapeng Deng0Qichang Wang1Huihui Xu2Guoqing Li3Su Liu4Yixiao Chen5Fei Yu6Weiqiang Yan7Hui Zeng8Peng Liu9National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaDepartment of Radiology, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaNational & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaOsteosarcoma is an aggressive malignant neoplasm, and it is of great significance to the fabrication and investigation of the anti-tumor mechanism of nanomedicine in the treatment of osteosarcoma. Herein, a cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-<i>b</i>-P(C7-<i>co</i>-CA)) was fabricated, and the anti-osteosarcoma mechanism of mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelle was investigated. mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles were prepared by self-assembly method, and their diameter was 227 nm. mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles could regulate the cell cycle and inhibit the proliferation of 143B cells, which was demonstrated by flow cytometry analysis, CCK-8 assay and 5-Ethynyl-2′-deoxyuridine (EdU) staining. The wound-healing assay and transwell assay showed that mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles effectively inhibited the migration and invasion of 143B cells. It was proven that mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles downregulated the levels of proliferation and apoptosis-related proteins and affected osteosarcoma migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). In addition, mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles can also inhibit the transcriptional activity of the PI3K/Akt signaling pathway. Therefore, these findings provide new evidence for the pharmacological effects of mPEG-<i>b</i>-P(C7-<i>co</i>-CA) micelles.https://www.mdpi.com/2227-9059/11/6/1524cinnamaldehyde prodrugosteosarcoma targetingPI3K/Aktmicelles
spellingShingle Jiapeng Deng
Qichang Wang
Huihui Xu
Guoqing Li
Su Liu
Yixiao Chen
Fei Yu
Weiqiang Yan
Hui Zeng
Peng Liu
A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro
Biomedicines
cinnamaldehyde prodrug
osteosarcoma targeting
PI3K/Akt
micelles
title A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro
title_full A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro
title_fullStr A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro
title_full_unstemmed A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro
title_short A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro
title_sort systematic study of anti osteosarcoma mechanism of ph sensitive charge conversion cinnamaldehyde polymeric prodrug micelles in vitro
topic cinnamaldehyde prodrug
osteosarcoma targeting
PI3K/Akt
micelles
url https://www.mdpi.com/2227-9059/11/6/1524
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