Redox poly(ethylene glycol)-b-poly(l-lactide) micelles containing diselenide bonds for effective drug delivery

Abstract

Bioreducible polymers have appeared as the ideal drug carriers for tumor therapy due to their properties of high stability in extracellular circulation and rapid drug release in intracellular reducing environment. Recently, the diselenide bond has emerged as a new reduction-sensitive linkage. In this work, the amphiphilic poly(ethylene glycol)-b-poly(L-lactide) containing diselenide bond has been synthesized and used to load anti-tumor drug, docetaxel (DTX), to form the redox micelles. It was found that the redox micelles showed a rapid response to glutataione (GSH), which resulted in a fast release of DTX in the presence of GSH. In contrast, <40 % of DTX was released from the micelles within 72 h under the normal condition (absence of GSH). The DTX-loaded redox micelles showed the significant inhibition effect to MCF-7 cells, and the cytotoxicity was dependent on the intracellular GSH concentrations. Moreover, considering the potentially clinical applications of the micelles through intravenous injection, the blood compatibility was also studied by the hemolysis analysis, activated partial thromboplastin time, prothrombin time and thromboelastography assays. These results confirmed that the redox micelles showed good blood safety, suggesting a potential application in tumor therapy.

Diselenide‐bearing crosslinked micelles‐reduced and stabilized gold nanoparticles in‐situ

“…Before sealing it with rubber plugs, sodium borohydride (1.134 g, 30 mmol) dissolved in 15 ml of water was added dropwise to the reaction vessel at 30 C. After 2 h of reaction, the temperature was increased to 60 C, and the reaction continued for 2 h until burgundy Na 2 Se 2 appeared. 8,34 The obtained solution was used directly in the next experiment, without separation. 4-bromine phenethylamine (6.03 g, 3 mmol) was dissolved in THF (20 ml) and then injected dropwise into the Na 2 Se 2 solution and maintained overnight at 60 C. The reaction liquid was extracted once using 30 ml of anhydrous dichloromethane (DCM) and divided into two layers.…”

Selenium-Containing Polymers: Perspectives toward Diverse Applications in Both Adaptive and Biomedical Materials

“…After this study of diselenide-containing polymer, more diselenide-containing drug delivery systems were developed, including micelles, hydrogels, and metal–organic frameworks (MOFs), which released drugs in response to oxidation, , reduction, − or dual redox stimuli. − Zhang and co-workers reported the fabrication of diselenide-containing supramolecular polymers, which were synthesized by mixing diselenide-containing monomer (FGGC11Se) 2 with cucurbit[8]­uril (CB[8]) . The monomer was composed of a diselenide bond linked with two undecyl chains and two tripeptides of Phe-Gly-Gly (FGG) as end groups.…”

Redox-sensitive doxorubicin liposome: a formulation approach for targeted tumor therapy

“…Similar to disulfide (S–S), the diselenide bond is cleaved upon exposure to the redox conditions of the TME. However, the bond energy to cleave the Se–Se bond is lower (172 kJ/mole) compared to that of the S–S bond (240 kJ/mole), leading to easier breakage of diselenide bonds 29 . The presence of oxidants could cleave and oxidize the Se–Se bonds to seleninic acid, while a reducing environment, reduces it to selenol 27 .…”