AbstractA series of tertiary amine containing PHMEMA-PEG-PHMEMA ABA triblock copolymers were synthesized by atom transfer radical polymerization (ATRP) using bromine-capped poly(ethylene glycol) (Br-PEG-Br) and 2-(hexamethyleneimino)ethyl methacrylate (HMEMA) as macro-initiator and monomers, respectively. The chemical structures and molecular weights of triblock copolymers were characterized by 1H NMR and gel permeation chromatography (GPC). The self-assembly behaviors of copolymers in different pH conditions were studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Triblock copolymers self-assembled into micelles in water (pH 7.4) and the micelles disassembled at acidic pH (pH 5.0). Anticancer drug doxorubicin (DOX) was used as a drug model and physically encapsulated into polymeric micelles. The drug release of DOX-loaded polymeric micelles was pH-responsive; the drug-loaded micelles that had higher contents of tertiary amine in polymer pendant groups showed faster release speed. In addition, the drug-loaded micelles showed excellent inhibition efficacy against HeLa cells in vitro. 相似文献
Well-defined p H-responsive poly(ε-caprolactone)-graft-β-cyclodextrin-graft-poly(2-(dimethylamino)ethylmethacrylate)-co-poly(ethylene glycol) methacrylate amphiphilic copolymers(PCL-g-β-CD-g-P(DMAEMA-co-PEGMA)) were synthesized using a combination of atom transfer radical polymerization(ATRP),ring opening polymerization(ROP) and "click" chemistry.Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy(FTIR),proton nuclear magnetic resonance(1H-NMR),and gel permeation chromatography(GPC).Then,the polymers could selfassemble into micelles in aqueous solution,which was demonstrated by dynamic light scattering(DLS) and transmission electron microscopy(TEM).The p H-responsive self-assembly behavior of these copolymers in water was investigated at different p H values of 7.4 and 5.0 for controlled doxorubicin(DOX) release,and these results revealed that the release rate of DOX could be effectively controlled by altering the p H,and the release of drug loading efficiency(DLE) was up to 88%(W/W).CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility,whereas the DOX-loaded micelles remained with high cytotoxicity for He La cells.Moreover,confocal laser scanning microscopy(CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect.The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX.These results successfully indicated that p H-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release. 相似文献
Internalization of drug delivery micelles into cancer cells is a crucial step for antitumor therapeutics. Novel amphiphilic star-shaped copolymers with zwitterionic phosphorylcholine (PC) block, 6-arm star poly(ε-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (6sPCL-b-PMPC), have been developed for encapsulation of poorly water-soluble drugs and enhancement of their cellular uptake. The star-shaped copolymers were synthesized by a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The copolymers self-assembled to form spherical micelles with low critical micelle concentration (CMC). The sizes of the micelles range from 80 to 170 nm and increase 30 ≈ 80% after paclitaxel (PTX) loading. Labeled with fluorescein isothiocyanate (FITC), the micelles were confirmed by fluorescence microscopy to have been internalized efficiently by tumor cells. Direct visualization of the micelles within tumor cells by transmission electron microscopy (TEM) confirmed that the 6sPCL-b-PMPC micelles were more efficiently uptaken by tumor cells compared to PCL-b-PEG micelles. When incorporated with PTX, the 6sPCL-b-PMPC micelles show much higher cytotoxicity against Hela cells than PCL-b-PEG micelles, in response to the higher efficiency of cellular uptake. 相似文献
A new type of fluorescent polymeric micelles is developed by self‐assembly from a series of amphiphilic block copolymers, poly(ethylene glycol)‐b‐poly[styrene‐co‐(2‐(1,2,3,4,5‐pentaphenyl‐1H‐silol‐1‐yloxy)ethyl methacrylate)] [PEG‐b‐P(S‐co‐PPSEMA)]. Their capability of loading doxorubicin (DOX) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles. Förster resonance energy transfer from PPSEMA to DOX is observed in DOX‐loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles. The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX‐loaded micelles.
Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71D3)‐based micelles effectively encapsulate the doxorubicin (DOX) with a high drug‐loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296D1) vesicles. DOX released from the resultant P71D3/DOX micelles is approximately 1.3‐fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71D3/DOX micelles also enhance drug potency in breast cancer MDA‐MB‐231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy‐dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.
pH‐sensitive polymers can be defined as polyelectrolytes that include in their structure weak acidic or basic groups that either accept or release protons in response to a change in the environmental pH. This work summarizes the design, synthesis, and potential applications of pH‐responsive fluorescent copolymers in the biomedical field. This was achieved using atom transfer radical polymerization (ATRP) of tert‐butyl acrylate using a CuBr/N,N,N′,N″N″‐pentamethyldiethylenetriamine catalyst system in conjunction with an alkyl bromide as the initiator. Well‐defined macroinitiators based on poly(tert‐butyl acrylate) with narrow molecular weight distributions were obtained by the addition of an appropriate solvent system in order to create a homogeneous catalytic system. The addition of n‐butyl acrylate as a second building block in order to create well‐defined poly(tert‐butyl acrylate)‐b‐poly(n‐butyl acrylate) block copolymers (PtBA‐b‐PnBA) followed by chemical modification of the block copolymers and functionalization with an appropriate fluorescent compound are the basis for the preparation of well‐defined fluorescent pH‐sensitive micelles. Thus, prepared water soluble nanosized pH‐sensitive micelles consisting of hydrophobic poly(n‐butyl acrylate) core and hydrophilic polyacrylic acid shell decorated with an appropriate fluorescent compound determined their potential applications of these systems in the field of biomedicine as biosensors, controlled drug delivery systems, and so on. In this respect, the cell viability and internalization of the polymer micelles were studied. 相似文献