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Doxorubicin Encapsulated in TPGS‐Modified 2D‐Nanodisks Overcomes Multidrug Resistance
Author(s) -
Jiang Tingting,
Zhang Changchang,
Sun Wenjie,
Cao Xueyan,
Choi Goeun,
Choy JinHo,
Shi Xiangyang,
Guo Rui
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905097
Subject(s) - doxorubicin , multiple drug resistance , efflux , pharmacology , in vivo , chemistry , drug , drug delivery , in vitro , drug resistance , p glycoprotein , polyethylene glycol , chemotherapy , medicine , biochemistry , biology , microbiology and biotechnology , antibiotics , organic chemistry
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.