Reduction-sensitive polymeric nanocarriers in cancer therapy: a comprehensive review

Abstract

Redox potential is regarded as a significant signal to distinguish between the extra-cellular and intra-cellular environments, as well as between tumor and normal tissues. Taking advantage of this physiological differentiation, various reduction-sensitive polymeric nanocarriers (RSPNs) have been designed and explored to demonstrate excellent stability during blood circulation but rapidly degrade and effectively trigger drug release in tumor cells. Therefore, this smart RSPN delivery system has attracted much attention in recent years, as it represents one of the most promising drug delivery strategies in cancer therapy. In this review, we will provide a comprehensive overview of RSPNs with various reducible linkages and functional groups up to date, including their design and synthetic strategies, preparation methods, drug release behavior, and their in vitro and in vivo efficacy in cancer therapy. In addition, dual- and triple-sensitive nanocarriers based on reducible disulfide bond-containing linkages will also be discussed.

Effects of copolymer component on the properties of phosphorylcholine micelles

“…27,29 Especially, the values for the PCL 20 -ss-PMPC 10 and PCL 20 -PMPC 10 were almost equal, meaning that the zwitterionic copolymers with/without disulfide might load drugs similarly. Moreover, when the MPC or CL unit changed, the K v values showed the same trend to CMC, ie, with the increase in the hydrophilic content or the decrease in the hydrophobic content, the K v value increased.…”

“…With the increase in hydrophilic units or the decrease in hydrophobic units, the CMC values increased. 28 Hence, the CMC value for PCL 20 -ss-PMPC 10 was the maximum in reductive phosphorylcholine copolymers and was close to the value of PCL 20 -PMPC 10 .…”

“…To our knowledge, studies concerning block copolymer constituent on phosphorylcholine micelle properties have not yet been reported. Furthermore, in the reports about the reductive drug carrier, 10 few works dealing with reductive phosphorylcholine micelles are reported.…”

“…9 Generally, redoxresponsive drug carriers are prepared from reducible polymers. 10 One of the most widely used strategies is to introduce the disulfide to serve as the linkage of the hydrophilic block and the hydrophobic block. [11][12][13] Recently, polymer micelles with zwitterionic phosphorylcholine as hydrophilic shells have been used as drug delivery systems.…”

Bioreducible cross-linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells

“…17,18 Although redox states in cancer cells are controlled by complex and variable parameters, 19 nevertheless, the ranges of redox potential are sufficient that polymers can in principle be designed to respond differentially in specific cells for tumour selective drug delivery. The most-established chemistries for inducing reductive responses into polymers are those based on disulfide linkages 20 . These are relatively stable in normal extracellular environments but undergo rapid cleavage in the presence of reducing agents and reactive thiols, such as glutathione (GSH), when inside intracellular components.…”