2210-03-9Relevant articles and documents
Unprecedented access to functional biodegradable polymers and coatings
Wang, Rong,Chen, Wei,Meng, Fenghua,Cheng, Ru,Deng, Chao,Feijen, Jan,Zhong, Zhiyuan
, p. 6009 - 6016 (2011)
The ever-growing biomedical technology such as tissue engineering, regenerative medicine, and controlled drug release intimately relies on the development of advanced functional biomaterials. Here, we report on versatile and robust synthesis of novel vinyl sulfone (VS)-functionalized biodegradable polymers that offer unprecedented access to advanced functional biodegradable polymers and coatings through selective Michael-type conjugate reaction with thiol-containing molecules. VS-functionalized biodegradable polymers including poly(ε-caprolactone) (PCL), poly(l-lactide) (PLA), and poly(trimethylene carbonate) (PTMC) were conveniently prepared with controlled molecular weights and functionalities through ring-opening copolymerization of ε-caprolactone (ε-CL), l-lactide (LA), or trimethylene carbonate (TMC) with a new cyclic carbonate monomer, vinyl sulfone carbonate (VSC), in toluene at 110 °C using isopropanol as an initiator and stannous octoate as a catalyst. Interestingly, these VS-functionalized biodegradable polymers allowed quantitative modification, without aid of a catalyst, with various thiol-containing molecules including 2-mercaptoethanol, cystamine, cysteine, GRGDC peptide, and thiolated poly(ethylene glycol) (PEG-SH) at a ligand-SH/VS molar ratio of 2/1 in DMF at room temperature, confirming that the Michael-type conjugate addition to VS is highly selective and tolerant to most other functional groups including hydroxyl, carboxyl, and amine. Remarkably, results of contact angle measurements, X-ray photoelectron spectroscopy (XPS), and fluorescence studies showed that biodegradable coatings based on these VS-functionalized polymers allowed direct, efficient, and clean (without catalyst and byproduct) surface functionalization with thiol-containing molecules in aqueous conditions, which is unprecedented and opens a new avenue to surface functionalization of medical implants as well as cell and tissue scaffolds. The preliminary cell culture studies using MG6 cells showed that unmodified VS-functionalized PCL films, similar to tissue culture plate, could well support cell attachment and growth, indicating that VS-functionalized PCL film is nontoxic and biocompatible. The surface of VS-functionalized PCL films could be elegantly engineered with thiolated nonfouling polymers (e.g., PEG and glycol chitosan) or cell adhesive motif (GRGDC peptide) to control cell attachment and growth. We are convinced that these vinyl sulfone-functionalized biodegradable polymers have a tremendous potential in biomedical engineering.
Synthesis and polymerization of alkyl halide-functional cyclic carbonates
Mindemark, Jonas,Bowden, Tim
, p. 5716 - 5722 (2011)
To increase the diversity in functional aliphatic polycarbonates, a series of novel chloro- and bromo-functional six-membered cyclic carbonate monomers were synthesized. Despite asymmetry in the monomer functionalities, homopolymerization of the monomers afforded semicrystalline polycarbonates with a high tendency to crystallize from the melt and/or on precipitation from a THF solution. Melting points were found in the 90-105 °C or 120-155 °C range for polymers comprising methyl or ethyl moieties, respectively, in the backbone. The monomers were further copolymerized with trimethylene carbonate to form random copolymers. Even among some of these random copolymers elements of semicrystallinity were found as confirmed by melting endotherms in DSC. The results clearly show that the incorporation of alkyl halide functionalities in aliphatic polycarbonates may lead to materials with a high ability to form crystallites, even in random copolymers, likely driven by polar interactions due to the presence of the halide functionalities.
Reversible core-crosslinked nanocarriers with pH-modulated targeting and redox-controlled drug release for overcoming drug resistance
Dan Zhao,Ma, Shujie,Yi, Xiaoqing,Cheng, Sixue,Zhuo, Renxi,Li, Feng
, p. 8399 - 8407 (2017)
Herein, a pH and redox dual-sensitive core-crosslinked targeting nanocarrier was prepared and used for co-delivery of doxorubicin (DOX) and tariquidar (TQR). The nanocarrier not only had excellent stability but also prevented the leakage of the drug in the normal physiological environment efficiently. Meanwhile, the targeting function of nanocarriers could also be suppressed in the normal physiological environment, protecting nanocarriers from being captured by RAW264.7 cells. Under mild acidic conditions, the targeting function was regained, leading to an effective tumor cell uptake of the nanocarrier. Furthermore, reduction-responsive drug release would occur in the cytoplasm due to the collapse of the reduction-sensitive crosslinked structure in the nanocarrier. By means of ligand-receptor mediated endocytosis and TQR-mediated glycoprotein (P-gp) inhibition, the IC50 value of DOX to MCF-7/ADR cells reduced from more than 100 μg mL-1 to 8.55 μg mL-1, exhibiting great potential in overcoming drug resistance.
ROS-Responsive Chalcogen-Containing Polycarbonates for Photodynamic Therapy
Yu, Li,Yang, Yue,Du, Fu-Sheng,Li, Zi-Chen
, p. 2182 - 2193 (2018/05/14)
Reactive oxygen species (ROS)-responsive polymers have attracted attention for their potential in photodynamic therapy. Herein, we report the ROS-responsive aliphatic polycarbonates prepared by the ring-opening polymerization (ROP) of three six-membered cyclic carbonate monomers with ethyl selenide, phenyl selenide or ethyl telluride groups. Under catalysis of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), all three monomers underwent the controlled anionic ROP, showing a feature of equilibrium polymerization due to the bulky effect of 5,5-disubstituents. With PEG macroinitiator, three series amphiphilic block copolymers were prepared. They could form spherical nanoparticles of ～100 nm, which were stable in neutral phosphate buffer but dissociated rapidly under triggering of H2O2. We studied the H2O2-induced oxidation profiles of selenide- or telluride-containing small molecules by 1H NMR and revealed the factors that affect the oxidation kinetics and products. On this basis, the oxidative degradation mechanism of the copolymer nanoparticles has been clarified. Under the same oxidative condition, the telluride-containing nanoparticle degraded with the fastest rate while the phenyl selenide-based one degraded most slowly. These ROS-responsive nanoparticles could load photosensitizer chlorin e6 (Ce6) and anticancer drug doxorubicin (DOX). Under red light irradiation, Ce6-sensitized production of 1O2 that triggered the degradation of nanoparticles, resulting in an accelerated payload release. In vitro cytotoxicity assays demonstrate that the nanoparticles coloaded with DOX and Ce6 exhibited a synergistic cell-killing effect to MCF-7 cells, representing a novel responsive nanoplatform for PDT and/or chemotherapy.
