Doxorubicin Encapsulated in TPGS-Modified 2D-Nanodisks Overcomes Multidrug Resistance.
Tingting JiangChangchang ZhangWenjie SunXueyan CaoGoeun ChoiJin-Ho ChoyXiangyang ShiRui GuoPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2020)
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.
Keyphrases
- multidrug resistant
- drug resistant
- breast cancer cells
- drug release
- adverse drug
- drug delivery
- acinetobacter baumannii
- cancer therapy
- induced apoptosis
- locally advanced
- signaling pathway
- cell proliferation
- photodynamic therapy
- single cell
- emergency department
- cell death
- endoplasmic reticulum stress
- electronic health record