Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer
Abstract A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge...
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| Format: | Article |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57296-4 |
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| author | Fahimeh Badparvar Ahmad Poursattar Marjani Roya Salehi Fatemeh Ramezani |
| author_facet | Fahimeh Badparvar Ahmad Poursattar Marjani Roya Salehi Fatemeh Ramezani |
| author_sort | Fahimeh Badparvar |
| collection | DOAJ |
| description | Abstract A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors. |
| first_indexed | 2024-04-24T09:54:03Z |
| format | Article |
| id | doaj.art-2f4bc7bbbe3747dbb75ca4191b788655 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2025-03-20T16:13:25Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2f4bc7bbbe3747dbb75ca4191b7886552024-09-01T11:13:52ZengNature PortfolioScientific Reports2045-23222024-04-0114112010.1038/s41598-024-57296-4Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancerFahimeh Badparvar0Ahmad Poursattar Marjani1Roya Salehi2Fatemeh Ramezani3Department of Organic Chemistry, Faculty of Chemistry, Urmia UniversityDepartment of Organic Chemistry, Faculty of Chemistry, Urmia UniversityDrug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical SciencesDepartment of Medical Nanotechnology, School of Advanced Medical Sciences, Tabriz University of Medical SciencesAbstract A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors.https://doi.org/10.1038/s41598-024-57296-4Nano drug delivery systems (NDDSs)pH/redox dual-responsiveCopolymeric nanoparticlesTumor microenvironment (TME) |
| spellingShingle | Fahimeh Badparvar Ahmad Poursattar Marjani Roya Salehi Fatemeh Ramezani Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer Scientific Reports Nano drug delivery systems (NDDSs) pH/redox dual-responsive Copolymeric nanoparticles Tumor microenvironment (TME) |
| title | Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer |
| title_full | Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer |
| title_fullStr | Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer |
| title_full_unstemmed | Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer |
| title_short | Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer |
| title_sort | dual ph redox responsive hyperbranched polymeric nanocarriers with tme trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer |
| topic | Nano drug delivery systems (NDDSs) pH/redox dual-responsive Copolymeric nanoparticles Tumor microenvironment (TME) |
| url | https://doi.org/10.1038/s41598-024-57296-4 |
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