Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Abstract

Introduction The development of nanodrug carriers utilizing tumor microenvironment has become a hotspot in reversing multidrug resistance (MDR). Materials and methods This study synthesized a redox-sensitive copolymer, Pluronic F127-disulfide bond- d -α-tocopheryl polyethylene glycol 1000 succinate (FSST), through the connection of the reduction-sensitive disulfide bond between F127 and d -α-tocopheryl polyethylene glycol 1000 succinate. This polymer could induce the elevation of reactive oxygen species (ROS) levels, ultimately resulting in cytotoxicity. Moreover, the redox-responsive mixed micelles, F127-folate (FA)/FSST/P123 (FFSSTP), based on FSST, Pluronic F127-FA, and Pluronic P123, were prepared to load paclitaxel (PTX). Results The in vitro release study demonstrated that FFSSTP/PTX accelerated the PTX release through the breakage of disulfide bond in reductive environment. In cellular experiment, FFSSTP/PTX induced significant apoptosis in PTX-resistant MCF-7/PTX cells through inhibiting adenosine triphosphate (ATP)-binding cassette proteins from pumping out PTX by interfering with the mitochondrial function and ATP synthesis. Furthermore, FFSSTP/PTX induced apoptosis through elevating the intracellular levels of ROS. Conclusion FFSSTP could become a potential carrier for the treatment of MDR tumors.

pH-triggered charge-reversal and redox-sensitive drug release polymer micelles co-deliver doxorubicin and triptolide for prostate tumor therapy

“…As shown in Figure 5A and B, the DA-cc-DT nanoparticles were stable under different environments, even stable in 10 mM GSH after incubated for 24 hours, while the size of DA-ss-DT nanoparticles increased from 155 to 880 nm and the polydispersity index (PDI) changed from 0.21 to 0.73 (data not shown) after incubating with 10 mM GSH for 8 hours, which may contribute to the cleavage of the disulfide bond under reduction environments. 24,47 Moreover, when incubation time prolonged to 24 hours, the size of DA-ss-DT changed to 970 nm, and the PDI was 0.82.…”

“…[19][20][21] In addition, the concentration of glutathione (GSH) is different between the extracellular (~2.0-20 µM) and intracellular (~10 mM) environments. [22][23][24] Moreover, the concentration of GSH in many tumors has been reported to be fourfold higher than that of normal tissues. 18,25 Therefore, the pH-and redox-responsive drug delivery system has been widely used in cancer therapy.…”

<p>Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy</p>

“…The CMC of the well-designed polymers were significantly lower than those of low molecular weight surfactants, such as Pluronic F127 (0.24 mg/ mL). 49 Moreover, the relatively low CMC was beneficial for maintaining the stability of polymeric micelles in blood circulation before reaching the target sites. 26…”

pH and redox dual-responsive copolymer micelles with surface charge reversal for co-delivery of all-<em>trans</em>-retinoic acid and paclitaxel for cancer combination chemotherapy

“…Moreover, the concentration of glutathione (GSH) in the cytoplasm (about 2-10 mM) is 100-1000-fold higher than that in the extracellular compartment. 23,[35][36][37] In addition, GSH levels are found to be further increased in tumor tissues compared to those in the normal tissues. 35,[38][39][40] Thus, disulfide linkage-based drug nanocarriers are able to promote drug release in the tumor cells.…”