Enzymatic synthesis of selenium-containing amphiphilic aliphatic polycarbonate as an oxidation-responsive drug delivery vehicle

Abstract

Although functional aliphatic polycarbonates (APCs) have attracted prominent research interest as stimuli-responsive biomaterials, the majority of functional APCs are fabricated by detrimental organometallic catalysts or organo-catalysts. Herein, a facile synthetic strategy based on enzymatic polymerization was developed to construct a selenium-containing amphiphilic aliphatic polycarbonate (mPEG-b-CMP 45 ). Specifically, the selenium in its backbone framework underwent a hydrophobichydrophilic transition upon exposure to the abnormal ROS level of the tumor, thus providing a promising platform for ROS-triggered drug release. This amphiphilic mPEG-b-CMP 45 efficiently encapsulated doxorubicin (DOX) via self-assembly in aqueous solution and showed an excellent ability to regulate the release of DOX in response to H 2 O 2 at biologically relevant concentrations (100 mM).These DOX-loaded nanoparticles could easily be internalized into U87 cells and possess the inherent antitumor properties of DOX, while they exhibited much lower cytotoxicity in normal cells HL-7702.Moreover, in many cases, the introduction of selenium caused high cytotoxicity of the materials, but the cytotoxicity results in HL-7702 cells demonstrated the good biocompatibility of mPEG-b-CMP 45 .These collective data suggested the potential use of mPEG-b-CMP 45 as a biocompatible and smart drug delivery vehicle. a Determined by 1 H NMR. b The molecular weight and M w /M n were determined by GPC against PS standards. c Calculated by uorescence measurements using Nile Red as probe. d Measured by DLS. e HSPMC represents monomer 3-((3-hydroxypropyl)selanyl)propyl methyl carbonate. 6006 | RSC Adv., 2019, 9, 6003-6010 This journal is

Stimuli-Responsive Aliphatic Polycarbonate Nanocarriers for Tumor-Targeted Drug Delivery

“…Moreover, CLSM studies revealed an internalization efficiency and drug release inside the cancer cells. Yang et al [136] developed ROS-responsive nanocarriers based on selenium-containing amphiphilic APC. The DOX-loaded nanoparticles were rapidly disrupted under biologically relevant concentrations of H 2 O 2 , thus releasing the encapsulated drug for inducing cancer cells apoptosis.…”

Recent Advances in Stimuli‐Responsive Commodity Polymers

“…Examples of molecular entities incorporated into these polymers and responsible for stimuli‐responsive characteristics are summarized in Figure . Due to technological importance of particular interest are responses to pH, [ 1–5 ] temperature, [ 6–14 ] H 2 O, [ 15–21 ] redox agents, [ 22–28 ] CO 2 , [ 29–34 ] glucose, [ 35 ] enzyme, [ 36–38 ] electric [ 39 ] and/or magnetic field, [ 40–42 ] electromagnetic radiation, [ 43,44 ] and mechanical forces [ 45–48 ] which are discussed in this review.…”

“…A) Schematic illustration of synthesis of a series of ssPESs by polycondensation of SS‐diacid with various diols and their reductive degradation under reducing conditions (Adapted with permission [ 186 ] Copyright 2012, Wiley‐VCH GmbH); B) Chemical structure of MPEG‐P(BHD‐SS)‐MPEG, the formation of micelles by self‐assembly, and schematic illustration of the GSH‐induced drug release associated by self‐decomposition of the micellar carriers (Adapted with permission [ 187 ] Copyright 2015, American Chemical Society); C) Chemical structure of polycarbonates with thioketal unit in sidechain, and schematic illustration of ROS induced self‐cleavage (Adapted with permission [ 26 ] Copyright 2019, American Chemical Society); D) ROS‐triggered degradation of the self‐assembled selenide containing polymer nanomaterials based on the selenoxide elimination reaction (Adapted with permission [ 25 ] Copyright 2019, The Royal Society of Chemistry); E) The synthesis of selenide‐based block copolymers and preparation of DOX‐loaded micelles as oxidation responsive drug delivery vehicle (Adapted under the terms of the Creative Commons Attribution 3.0 Unported License. [ 27 ] Copyright 2019, The Royal Society of Chemistry); F) Self‐assembly of thioether‐based block copolymers and their oxidation behavior (Adapted with permission [ 188 ] Copyright 2018, The Royal Society of Chemistry).…”

“…A series of selenide‐based polycarbonates have been examined for ROS responsiveness (H 2 O 2 ) at tumor cells relevant concentrations (Figure 5E). [ 27 ] The capability of self‐assembling into nanoparticles with guest molecules encapsulated inside is enhanced by the amphipathic copolymer blocks. The desirable average diameters (<200 nm) tend to maintain a minimal renal excretion, low‐level uptake by the reticuloendothelial system, effectively enhanced permeation, and retention effect for passive tumor targeting.…”

Lipase-catalyzed synthesis and post-polymerization modification of new fully bio-based poly(hexamethylene γ-ketopimelate) and poly(hexamethylene γ-ketopimelate-co-hexamethylene adipate) copolyesters

“…Enzymatic polymerization provides a new path for the synthesis of functionalized polyester materials with lots of advantages, such as high catalytic activity, high selectivity, mild reaction conditions, and the use of green biocatalysts (28)(29)(30)(31)(32). In recent years, especially cheap and readily available lipase has attracted extensive attention in the synthesis of bio-based polyesters, owing to the fact that both monomers and catalysts come from renewable resources (33)(34)(35)(36)(37).…”