Doxorubicin Encapsulated in TPGS‐Modified 2D‐Nanodisks Overcomes Multidrug Resistance

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.