Doxorubicin Encapsulated in TPGS‐Modified 2D‐Nanodisks Overcomes Multidrug Resistance. Issue 11 (4th February 2020)

• Record Type: Journal Article
• Authors: Jiang, Tingting; Zhang, Changchang; Sun, Wenjie; Cao, Xueyan; Choi, Goeun; Choy, Jin‐Ho; Shi, Xiangyang; Guo, Rui
• Is Part Of: Chemistry. Volume 26:Issue 11(2020)
• Page Start: 2470
• Page End: 2477
• Publication Date: 2020-02-04
• Subjects: doxorubicin -- drug delivery -- laponite nanodisks -- multidrug resistance -- d-alpha-tocopheryl polyethylene glycol 1000 succinate; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201905097
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Multidrug resistance (MDR) is regarded as a main obstacle for effective chemotherapy, and P‐glycoprotein (P‐gp)‐mediated drug efflux has been demonstrated to be the key factor responsible for MDR. In this study, a novel pH‐responsive hybrid drug delivery system was developed by conjugating d ‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS), a kind of P‐gp inhibitor, on the surface of laponite nanodisks to overcome MDR. The prepared LM‐TPGS display excellent colloidal stability, a high encapsulation efficiency of doxorubicin (DOX), and a pH‐responsive drug release profile. In vitro experiments verified that LM‐TPGS/DOX could exhibit significantly enhanced therapeutic efficacy in treating DOX‐resistant breast cancer cells (MCF‐7/ADR) through inhibiting the activity of P‐gp‐mediated drug efflux and effectively accumulating DOX within cancer cells. In vivo results revealed that LM‐TPGS/DOX outstandingly suppressed MCF‐7/ADR tumors with low side effects. Therefore, the high drug payload, enhanced inhibition efficacy to drug‐resistant cells, and low side effects make the LM‐TPGS/DOX a promising nanoplatform to reverse MDR for effective chemotherapy. Abstract : Overcoming drug resistance : A novel pH‐responsive hybrid drug delivery system was developed by conjugating d ‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS), a kind of P‐glycoprotein (P‐gp) inhibitor, on the surface of laponite nanodisks to overcome multidrug resistance (MDR). The prepared LM‐TPGS/DOX nanodisks could efficiently deliver doxorubicin (DOX) to DOX‐resistant cancer cells, by inhibiting the activity of P‐gp‐mediated drug efflux and accumulating DOX within cells, and perform outstanding suppression of tumors with low side effects by reversing MDR.