mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy
Abstract Background Tyrosine kinase inhibitors (TKIs) that act against the epithelial growth factor receptor (EGFR) were once widely used in chemotherapy for many human cancers. However, acquired chemoresistance occurred in almost all patients, limiting the clinical application of EGFR-TKI. Thus far...
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| Format: | Article |
| Language: | English |
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BMC
2017-10-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-017-0302-5 |
| _version_ | 1811303279131361280 |
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| author | Yan Zheng Chang Su Liang Zhao Yijie Shi |
| author_facet | Yan Zheng Chang Su Liang Zhao Yijie Shi |
| author_sort | Yan Zheng |
| collection | DOAJ |
| description | Abstract Background Tyrosine kinase inhibitors (TKIs) that act against the epithelial growth factor receptor (EGFR) were once widely used in chemotherapy for many human cancers. However, acquired chemoresistance occurred in almost all patients, limiting the clinical application of EGFR-TKI. Thus far, no effective methods existing can resolve this problem. Designing a therapeutic treatment with a specific multi-target profile has been regarded as a possible strategy to overcome acquired EGFR-TKI resistance. Methods MDR1 antibody-modified chitosan nanoparticles loading gefitinib and autophagy inhibitor chloroquine were prepared by ionic crosslinking and electrostatic attracting method. MTT assay, flow cytometry analysis and western blot assay were all performed to confirm the effect of different formulations of gefitinib on the proliferation of SMMC-7721/gefitinib cells. The preparations demonstrated their multi-target potential to achieve both tumor-targeting selectivity and the desired antitumor effects by blocking cell-surface MDR1 and inhibiting autophagy. Results mAb MDR1-modified CS NPs, when combined with the co-delivery of gefitinib and chloroquine, showed targeting and therapeutic potential on enhancing the delivery of anticancer drugs and inducing significant cell apoptosis against acquired EGFR-TKI resistance through the modulation of autophagy and while blocking the activity of the MDR1 receptor. Conclusions A new approach to design an excellent nanoparticle drug-delivery system can overcome acquired EGFR-TKI resistance against various multiple antitumor targets. |
| first_indexed | 2024-04-13T07:45:02Z |
| format | Article |
| id | doaj.art-c4e41fec06b14e8bb53608456082ca1d |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T07:45:02Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-c4e41fec06b14e8bb53608456082ca1d2022-12-22T02:55:44ZengBMCJournal of Nanobiotechnology1477-31552017-10-0115111110.1186/s12951-017-0302-5mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagyYan Zheng0Chang Su1Liang Zhao2Yijie Shi3School of Pharmacy, Jinzhou Medical UniversitySchool of Veterinary Medicine, Jinzhou Medical UniversitySchool of Pharmacy, Jinzhou Medical UniversitySchool of Pharmacy, Jinzhou Medical UniversityAbstract Background Tyrosine kinase inhibitors (TKIs) that act against the epithelial growth factor receptor (EGFR) were once widely used in chemotherapy for many human cancers. However, acquired chemoresistance occurred in almost all patients, limiting the clinical application of EGFR-TKI. Thus far, no effective methods existing can resolve this problem. Designing a therapeutic treatment with a specific multi-target profile has been regarded as a possible strategy to overcome acquired EGFR-TKI resistance. Methods MDR1 antibody-modified chitosan nanoparticles loading gefitinib and autophagy inhibitor chloroquine were prepared by ionic crosslinking and electrostatic attracting method. MTT assay, flow cytometry analysis and western blot assay were all performed to confirm the effect of different formulations of gefitinib on the proliferation of SMMC-7721/gefitinib cells. The preparations demonstrated their multi-target potential to achieve both tumor-targeting selectivity and the desired antitumor effects by blocking cell-surface MDR1 and inhibiting autophagy. Results mAb MDR1-modified CS NPs, when combined with the co-delivery of gefitinib and chloroquine, showed targeting and therapeutic potential on enhancing the delivery of anticancer drugs and inducing significant cell apoptosis against acquired EGFR-TKI resistance through the modulation of autophagy and while blocking the activity of the MDR1 receptor. Conclusions A new approach to design an excellent nanoparticle drug-delivery system can overcome acquired EGFR-TKI resistance against various multiple antitumor targets.http://link.springer.com/article/10.1186/s12951-017-0302-5EGFRTyrosine kinase inhibitorNanoparticlesGefitinibAutophagyChloroquine |
| spellingShingle | Yan Zheng Chang Su Liang Zhao Yijie Shi mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy Journal of Nanobiotechnology EGFR Tyrosine kinase inhibitor Nanoparticles Gefitinib Autophagy Chloroquine |
| title | mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy |
| title_full | mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy |
| title_fullStr | mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy |
| title_full_unstemmed | mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy |
| title_short | mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy |
| title_sort | mab mdr1 modified chitosan nanoparticles overcome acquired egfr tki resistance through two potential therapeutic targets modulation of mdr1 and autophagy |
| topic | EGFR Tyrosine kinase inhibitor Nanoparticles Gefitinib Autophagy Chloroquine |
| url | http://link.springer.com/article/10.1186/s12951-017-0302-5 |
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