Facile Construction of pH- and Redox-Responsive Micelles from a Biodegradable Poly(β-hydroxyl amine) for Drug Delivery

Abstract

Here we demonstrate a type of pH and reduction dual-sensitive biodegradable micelles, which were self-assembled by a cationic polymer in an aqueous solution. Due to tumor cells or tissues showing low pH and high reduction concentration, these micelles possessed specific tumor targetability and maximal drug-release controllability inside tumor cells upon changes in physical and chemical environments, but presented good stability at physiological conditions. CCK-8 assay showed that the DOX-loaded micelles had a similar cytotoxicity for MCF-7 tumor cells as free DOX, and blank micelles had a very low cytotoxicity to the cells. Fluorescent microscopy observation revealed that the drug-loaded micelles could be quickly internalized by endosomes to inhibit cancer cell growth. These results indicated these biodegradable micelles, as a novel and effective pH- and redox-responsive nanocarrier, have a potential to improve drug delivery and enhance the antitumor efficacy.

Assembly, Disassembly and Reassembly of Complex Coacervate Core Micelles with Redox‐Responsive Supramolecular Cross‐Linkers

“…[31,32] Among these specific stimuli, redox responsiveness is one of the most enticing one, for example to be exploited in cells and tissue with reducing environments. [11,[33][34][35] Based on the concept of redox responsivity, several studies have reported micellar dissociation in response to dithiothreitol (DTT) or glutathione (GSH) and consequential release of micelle-embedded cargo, such as DNA molecules, [36] doxorubicin, [9][10][11] and siRNA. [31] However, most of the redox-responsive micelles contain the redox responsive disulfide on the edge between the core and the shell; cleavage of the disulfide bonds on the shell does not always lead to a fully disassociated micellar core, which decreases the efficiency of release of the core-embedded molecules.…”

“…A similar behavior was described in literature for poly-hydroxylamine-based micelles. [11] The disulfide cleavage and reformation can be also observed by the naked eye. After treatment with 6 equivalents of DTT, the solution became partially clear due to the cleavage of disulfide bonds and subsequent disassembly of the micelles.…”

“…Coacervate-core micelle display high stability under physiological conditions, prolonged blood circulation, high gene transfection efficiency, low cytotoxicity and tunable imaging properties. [9][10][11][12][13][14][15] In the past decades, substantial knowledge on the way charged polymers assemble into coacervate micelles has been acquired. For example, it was shown that control over the micellar size and stability can be obtained by varying the individual (block) polymer lengths.…”

Reduction responsive and surface charge switchable polyurethane micelles with acid cleavable crosslinks for intracellular drug delivery

“…[1][2][3][4][5][6] The release of the payloads from these responsive micelles happens in a controlled manner on arrival at the target site, only when triggered by external stimuli, such as light, temperature, pH, redox potential, enzymes and ionic strength. [7][8][9][10][11][12] Recently, multi-responsive assemblies have been developed to optimize the release of functional species in different environments. Biodegradable multi-segmented polyurethanes (PUs) with stimuli responsive properties have been widely studied as drug carriers due to their good biocompatibilities and tailorable molecular structures.…”

Redox and pH Dual Responsive Polymer Based Nanoparticles for In Vivo Drug Delivery

“…The aim is to reduce side effects of cytotoxic anticancer drugs, while improving their therapeutic efficiency . A primary requirement for nanomaterials to be used for intended biological applications is their biocompatibility . Various nanomaterials ranging from inorganic nanoparticles (NPs) to polymeric liposomes have been reported as drug carriers .…”