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A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug
Jiapeng Deng1,2, Qichang Wang1,2, Huihui Xu1,2
1National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
Abstract:
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-b-P(C7-co-CA)) was fabricated, and the anti-osteosarcoma mechanism of mPEG-b-P(C7-co-CA) micelle was investigated. mPEG-b-P(C7-co-CA) micelles were prepared by self-assembly method, and their diameter was 227 nm. mPEG-b-P(C7-co-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-b-P(C7-co-CA) micelles effectively inhibited the migration and invasion of 143B cells. It was proven that mPEG-b-P(C7-co-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-b-P(C7-co-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-b-P(C7-co-CA) micelles.
Insights
This study developed pH-sensitive polymeric micelles (mPEG-b-P(C7-co-CA)) for osteosarcoma treatment. These micelles inhibit cancer cell proliferation, migration, and invasion by targeting key cellular pathways.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Oncology
Background:
- Osteosarcoma is an aggressive bone cancer requiring novel therapeutic strategies.
- Nanomedicine offers potential for targeted cancer treatment with reduced side effects.
- Developing effective anti-tumor mechanisms for nanomedicines is crucial for osteosarcoma therapy.
Purpose of the Study:
- To fabricate and investigate the anti-osteosarcoma mechanism of a novel cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-b-P(C7-co-CA)).
Main Methods:
- Fabrication of mPEG-b-P(C7-co-CA) micelles via self-assembly.
- Assessment of anti-proliferative effects using flow cytometry, CCK-8 assay, and EdU staining on 143B cells.
- Evaluation of anti-migratory and anti-invasive properties using wound-healing and Transwell assays.
- Analysis of protein expression related to proliferation, apoptosis, and epithelial-mesenchymal transition (EMT).
- Investigation of the PI3K/Akt signaling pathway's transcriptional activity.
Main Results:
- The fabricated mPEG-b-P(C7-co-CA) micelles exhibited a diameter of 227 nm.
- Micelles effectively inhibited 143B cell proliferation, migration, and invasion.
- Downregulation of proliferation and apoptosis-related proteins was observed.
- Inhibition of EMT was identified as a key mechanism for reduced migration and invasion.
- The micelles suppressed the transcriptional activity of the PI3K/Akt signaling pathway.
Conclusions:
- mPEG-b-P(C7-co-CA) micelles demonstrate significant anti-osteosarcoma effects.
- The observed pharmacological effects are mediated through cell cycle regulation, inhibition of proliferation, migration, invasion, and EMT, along with PI3K/Akt pathway suppression.
- These findings support the potential of mPEG-b-P(C7-co-CA) micelles as a therapeutic agent for osteosarcoma.
