A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer
Abstract Background Triple negative breast cancer (TNBC) is one of the most biologically aggressive breast cancers and lacks effective treatment options, resulting in a poor prognosis. Therefore, studies aiming to explore new therapeutic strategies for advanced TNBC are urgently needed. According to...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-02-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-00800-z |
| _version_ | 1811212559734276096 |
|---|---|
| author | Chuanrong Chen Ming Shen Hongze Liao Qianqian Guo Hao Fu Jian Yu Yourong Duan |
| author_facet | Chuanrong Chen Ming Shen Hongze Liao Qianqian Guo Hao Fu Jian Yu Yourong Duan |
| author_sort | Chuanrong Chen |
| collection | DOAJ |
| description | Abstract Background Triple negative breast cancer (TNBC) is one of the most biologically aggressive breast cancers and lacks effective treatment options, resulting in a poor prognosis. Therefore, studies aiming to explore new therapeutic strategies for advanced TNBC are urgently needed. According to recent studies, microRNA-124 (miR124) not only inhibits tumour growth but also increases the sensitivity of TNBC to paclitaxel (PTX), suggesting that a platform combining PTX and miR124 may be an advanced solution for TNBC. Results Herein, we constructed a stepped cleavable calcium phosphate composite lipid nanosystem (CaP/LNS) to codeliver PTX and miR124 (PTX/miR124-NP). PTX/miR124-NP exhibited superior tumor microenvironment responsive ability, in which the surface PEG layer was shed in the mildly acidic environment of tumor tissues and exposed oligomeric hyaluronic acid (o-HA) facilitated the cellular uptake of CaP/LNS by targeting the CD44 receptor on the surface of tumor cells. Inside tumour cells, o-HA detached from CaP/LNS due to the reduction of disulfide bonds by glutathione (GSH) and inhibited tumour metastasis. Then, PTX and miR124 were sequentially released from CaP/LNS and exerted synergistic antitumour effects by reversing the Epithelial-Mesenchymal Transition (EMT) process in MDA-MB-231 cells. Moreover, PTX/miR124-NP showed significant antitumour efficiency and excellent safety in mice bearing MDA-MB-231 tumours. Conclusion Based on these results, the codelivery of PTX and miR124 by the CaP/LNS nanosystem might be a promising therapeutic strategy for TNBC. |
| first_indexed | 2024-04-12T05:31:06Z |
| format | Article |
| id | doaj.art-28451436579a46dda740e775e3b3a12c |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-12T05:31:06Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-28451436579a46dda740e775e3b3a12c2022-12-22T03:46:05ZengBMCJournal of Nanobiotechnology1477-31552021-02-0119111710.1186/s12951-021-00800-zA paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancerChuanrong Chen0Ming Shen1Hongze Liao2Qianqian Guo3Hao Fu4Jian Yu5Yourong Duan6State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityResearch Center for Marine Drugs, State Key Laboratory of Oncogene and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Background Triple negative breast cancer (TNBC) is one of the most biologically aggressive breast cancers and lacks effective treatment options, resulting in a poor prognosis. Therefore, studies aiming to explore new therapeutic strategies for advanced TNBC are urgently needed. According to recent studies, microRNA-124 (miR124) not only inhibits tumour growth but also increases the sensitivity of TNBC to paclitaxel (PTX), suggesting that a platform combining PTX and miR124 may be an advanced solution for TNBC. Results Herein, we constructed a stepped cleavable calcium phosphate composite lipid nanosystem (CaP/LNS) to codeliver PTX and miR124 (PTX/miR124-NP). PTX/miR124-NP exhibited superior tumor microenvironment responsive ability, in which the surface PEG layer was shed in the mildly acidic environment of tumor tissues and exposed oligomeric hyaluronic acid (o-HA) facilitated the cellular uptake of CaP/LNS by targeting the CD44 receptor on the surface of tumor cells. Inside tumour cells, o-HA detached from CaP/LNS due to the reduction of disulfide bonds by glutathione (GSH) and inhibited tumour metastasis. Then, PTX and miR124 were sequentially released from CaP/LNS and exerted synergistic antitumour effects by reversing the Epithelial-Mesenchymal Transition (EMT) process in MDA-MB-231 cells. Moreover, PTX/miR124-NP showed significant antitumour efficiency and excellent safety in mice bearing MDA-MB-231 tumours. Conclusion Based on these results, the codelivery of PTX and miR124 by the CaP/LNS nanosystem might be a promising therapeutic strategy for TNBC.https://doi.org/10.1186/s12951-021-00800-zStepped cleavable nanoparticlesPaclitaxelMicroRNA-124Synergistic antitumour effectTriple negative breast cancer |
| spellingShingle | Chuanrong Chen Ming Shen Hongze Liao Qianqian Guo Hao Fu Jian Yu Yourong Duan A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer Journal of Nanobiotechnology Stepped cleavable nanoparticles Paclitaxel MicroRNA-124 Synergistic antitumour effect Triple negative breast cancer |
| title | A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer |
| title_full | A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer |
| title_fullStr | A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer |
| title_full_unstemmed | A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer |
| title_short | A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer |
| title_sort | paclitaxel and microrna 124 coloaded stepped cleavable nanosystem against triple negative breast cancer |
| topic | Stepped cleavable nanoparticles Paclitaxel MicroRNA-124 Synergistic antitumour effect Triple negative breast cancer |
| url | https://doi.org/10.1186/s12951-021-00800-z |
| work_keys_str_mv | AT chuanrongchen apaclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT mingshen apaclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT hongzeliao apaclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT qianqianguo apaclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT haofu apaclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT jianyu apaclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT yourongduan apaclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT chuanrongchen paclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT mingshen paclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT hongzeliao paclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT qianqianguo paclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT haofu paclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT jianyu paclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer AT yourongduan paclitaxelandmicrorna124coloadedsteppedcleavablenanosystemagainsttriplenegativebreastcancer |