Redox- and pH-Sensitive Polymeric Micelles Based on Poly(β-amino ester)-Grafted Disulfide Methylene Oxide Poly(ethylene glycol) for Anticancer Drug Delivery

Abstract

In this report, a redox- and pH-sensitive poly­(β-amino ester)-grafted disulfide methylene oxide poly­(ethylene glycol) (PAE-g-DSMPEG) was synthesized, and it showed not only a sharp pH-dependent assembly–disassembly transition but also a quick shell shading in a high concentration of reducing agent by Michael addition polymerization. 1H NMR, dynamic light scattering, and transition electron microscopy were combined to characterize the redox- and pH-responsiveness in various triggered conditions. The hydrophobic drug doxorubicin (DOX) was used as the model drug to investigate the encapsulation and delivery ability of polymeric micelles, in both in vitro and in vivo experiments. Notably, antitumor experiments in tumor-bearing mice showed that DOX-loaded polymeric micelles effectively enhanced the therapeutic efficacy in comparison to free-DOX. These results were further confirmed by histopathological examinations. Taken together, the results suggested that PAE-g-DSMPEG could be a potential hydrophobic drug delivery vehicle.

pH-sensitive micelles self-assembled from polymer brush (PAE-<em>g</em>-cholesterol)-<em>b</em>-PEG-<em>b</em>-(PAE-<em>g</em>-cholesterol) for anticancer drug delivery and controlled release

“…19 In the past decades, many stimuli-response polymers have been synthesized and used as drug carriers based on the differences between normal and targeted sites, including temperature, enzyme, pressure, etc. [20][21][22][23][24][25] As reported, extracellular pH of tumor is weakly acidic (about 6.5-7.2), and the pH values in endosome and lysosome are much lower (4.5~6.5), compared with the normal physiological pH of 7.4. [26][27][28] Therefore, increasing attention has been directed at pH-sensitive polymeric micelles.…”

Benzoic‐Imine‐Based Physiological‐pH‐Responsive Materials for Biomedical Applications

“…One approach for the construction of polymeric pH‐sensitive drug carriers is the use of pH‐responsive monomers with pK a around the target pH value. Some representative units, such as histidine, 2‐(diethylamino)ethyl methacrylate, sulfadimethoxine, acetal, hydrazine, and oligoester units, have been extensively utilized to induce pH sensitivity into polymers and, hence, the delivery agents for either passive targeting of tumor tissue or intracellular delivery . As an example, Bae′s group synthesized a series of block copolymers that contained poly( l ‐histidine) units, which has a pK a value of 6.8–7.0, to construct tumor‐targeting drugs and gene‐delivery vehicles.…”

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

“…[17][18][19][20][21][22][23][24] In particular, redox and pH dual-responsive DDSs were paid more attention because of the 40 existence of redox potential and pH gradient between the extraand intracellular space. [25][26][27][28][29][30][31][32][33][34] Inside the body, glutathione (GSH), a natural reducing agent for disulfide bonds, was found in the blood plasma at µM levels (approximately ~2 µM), due to rapid enzymatic degradation, whereas a substantially high 45 concentration at mM levels (2-10 mM) was found in the cytoplasm of cancer cells. 35 Beside, the pH at both primary and metastasized tumors is lower (6.5-7.2) than the pH of normal tissues (7.4) and intracellular pH of their endosomes (5.5-6.0) and lysosomes (4.5-5.0) are even more acidic.…”