pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy
TPGS approved by FDA can be used as a P-gp inhibitor to effectively reverse multi-drug resistance (MDR) and as an anticancer agent for synergistic antitumor effects. However, the comparatively high critical micelle concentration (CMC), low drug loading (DL) and poor tumor target limit its further cl...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-05-01
|
| Series: | Asian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087621000143 |
| _version_ | 1818436888792399872 |
|---|---|
| author | Yong Xu Shi Wang Longshun Yang Yuhang Dong Yafang Zhang Guoqing Yan Rupei Tang |
| author_facet | Yong Xu Shi Wang Longshun Yang Yuhang Dong Yafang Zhang Guoqing Yan Rupei Tang |
| author_sort | Yong Xu |
| collection | DOAJ |
| description | TPGS approved by FDA can be used as a P-gp inhibitor to effectively reverse multi-drug resistance (MDR) and as an anticancer agent for synergistic antitumor effects. However, the comparatively high critical micelle concentration (CMC), low drug loading (DL) and poor tumor target limit its further clinical application. To overcome these drawbacks, the pH-sensitive star-shaped TPGS copolymers were successfully constructed via using pentaerythritol as the initial materials, ortho esters as the pH-triggered linkages and TPGS active-ester as the terminated MDR material. The amphiphilic star-shaped TPGS copolymers could self-assemble into free and doxorubicin (DOX)-loaded micelles at neutral aqueous solutions. The micelles exhibited the lower CMC (8.2 × 10−5 mg/ml), higher DL (10.8%) and long-term storage and circulation stability, and showed enhanced cellular uptake, apoptosis, cytotoxicity, and growth inhibition for in vitro MCF-7/ADR and/or MCF-7/ADR multicellular spheroids and in vivo MCF-7/ADR tumors via efficiently targeted drug release at tumoral intracellular pH (5.0), MDR reversal of TPGS, and synergistic effect of DOX and TPGS. Therefore, the pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages are potentially useful to clinically transform for enhanced MDR cancer treatment. |
| first_indexed | 2024-12-14T17:15:56Z |
| format | Article |
| id | doaj.art-e13c2bdbbf004a6f88c6c34fb9200cba |
| institution | Directory Open Access Journal |
| issn | 1818-0876 |
| language | English |
| last_indexed | 2024-12-14T17:15:56Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-e13c2bdbbf004a6f88c6c34fb9200cba2022-12-21T22:53:26ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762021-05-01163363373pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapyYong Xu0Shi Wang1Longshun Yang2Yuhang Dong3Yafang Zhang4Guoqing Yan5Rupei Tang6Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaCorresponding authors.; Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaCorresponding authors.; Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaTPGS approved by FDA can be used as a P-gp inhibitor to effectively reverse multi-drug resistance (MDR) and as an anticancer agent for synergistic antitumor effects. However, the comparatively high critical micelle concentration (CMC), low drug loading (DL) and poor tumor target limit its further clinical application. To overcome these drawbacks, the pH-sensitive star-shaped TPGS copolymers were successfully constructed via using pentaerythritol as the initial materials, ortho esters as the pH-triggered linkages and TPGS active-ester as the terminated MDR material. The amphiphilic star-shaped TPGS copolymers could self-assemble into free and doxorubicin (DOX)-loaded micelles at neutral aqueous solutions. The micelles exhibited the lower CMC (8.2 × 10−5 mg/ml), higher DL (10.8%) and long-term storage and circulation stability, and showed enhanced cellular uptake, apoptosis, cytotoxicity, and growth inhibition for in vitro MCF-7/ADR and/or MCF-7/ADR multicellular spheroids and in vivo MCF-7/ADR tumors via efficiently targeted drug release at tumoral intracellular pH (5.0), MDR reversal of TPGS, and synergistic effect of DOX and TPGS. Therefore, the pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages are potentially useful to clinically transform for enhanced MDR cancer treatment.http://www.sciencedirect.com/science/article/pii/S1818087621000143TPGSOrtho estersStar-shaped copolymersMDR reversal |
| spellingShingle | Yong Xu Shi Wang Longshun Yang Yuhang Dong Yafang Zhang Guoqing Yan Rupei Tang pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy Asian Journal of Pharmaceutical Sciences TPGS Ortho esters Star-shaped copolymers MDR reversal |
| title | pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy |
| title_full | pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy |
| title_fullStr | pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy |
| title_full_unstemmed | pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy |
| title_short | pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy |
| title_sort | ph sensitive micelles self assembled from star shaped tpgs copolymers with ortho ester linkages for enhanced mdr reversal and chemotherapy |
| topic | TPGS Ortho esters Star-shaped copolymers MDR reversal |
| url | http://www.sciencedirect.com/science/article/pii/S1818087621000143 |
| work_keys_str_mv | AT yongxu phsensitivemicellesselfassembledfromstarshapedtpgscopolymerswithorthoesterlinkagesforenhancedmdrreversalandchemotherapy AT shiwang phsensitivemicellesselfassembledfromstarshapedtpgscopolymerswithorthoesterlinkagesforenhancedmdrreversalandchemotherapy AT longshunyang phsensitivemicellesselfassembledfromstarshapedtpgscopolymerswithorthoesterlinkagesforenhancedmdrreversalandchemotherapy AT yuhangdong phsensitivemicellesselfassembledfromstarshapedtpgscopolymerswithorthoesterlinkagesforenhancedmdrreversalandchemotherapy AT yafangzhang phsensitivemicellesselfassembledfromstarshapedtpgscopolymerswithorthoesterlinkagesforenhancedmdrreversalandchemotherapy AT guoqingyan phsensitivemicellesselfassembledfromstarshapedtpgscopolymerswithorthoesterlinkagesforenhancedmdrreversalandchemotherapy AT rupeitang phsensitivemicellesselfassembledfromstarshapedtpgscopolymerswithorthoesterlinkagesforenhancedmdrreversalandchemotherapy |