Synthesis and physicochemical characterization of amphiphilic block copolymers bearing acid-sensitive orthoester linkage as the drug carrier

Amphiphilic block copolymers bearing an acid-sensitive orthoester linkage, composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(γ-benzyl L-glutamate) (PBLG), were prepared as the carrier capable of selectively releasing the hydrophobic drug at the mildly acidic condition. Diblock copolymers with various lengths of PBLG were synthesized via ring opening polymerization of benzyl glutamate NCA in the presence of the acid-labile PEG as a macroinitiator. Owing to their amphiphilicities, the copolymers formed spherical micelles in aqueous conditions, and their particle sizes (22-106 nm in diameter) were dependent on the block length of PBLG. These nanoparticles were stable in the physiological buffer (pH 7.4), whereas they were readily decomposed under the acidic condition. In particular, the block copolymer with a smaller hydrophobic portion was rapidly disassembled under the acidic condition. Doxorubicin (DOX), chosen as the model anti-cancer drug, was effectively encapsulated into the hydrophobic core of the micelles using the solvent casting method. The loading efficiency depended on the hydrophobic block length of the copolymer; i.e., the longer hydrophobic block allowed for loading of larger amounts of the drug. In vitro release studies demonstrated that DOX was slowly released from the pH-sensitive micelles in the physiological buffer (pH 7.4), whereas the release rate of DOX significantly increased under the acidic condition (pH 5.0). From the in vitro cytotoxicity test, it was found that DOX-loaded pH-sensitive micelles showed higher toxicity to SCC7 cancer cells than DOX-loaded micelles without the orthoester linker. These results suggest that the amphiphilic block copolymer bearing the orthoester linkage is useful for pH-triggered delivery of the hydrophobic drug.     

Intracellular pH‐sensitive dextran‐based micelles as efficient drug delivery platforms

As drug delivery systems, stimuli‐responsive polymer micelles hold great potential in cancer chemotherapeutics to improve therapeutic efficiency and eliminate organism adverse effects. Here, pH‐sensitive polymeric micelles based on dextran‐g‐benzimidazole were designed and used for intracellular anticancer drug delivery. The anticancer drug doxorubicin (DOX) was effectively loaded into the micelles via hydrophobic interactions. In vitro release studies demonstrated that the release of loaded DOX was greater and faster under acid conditions such as in carcinomatous areas (pH < 6.8) than in physiological conditions (pH 7.4). MTT assays and flow cytometric analyses showed that DOX‐loaded micelles had higher cellular proliferation inhibition towards HeLa and HepG2 cells than pH‐insensitive controls. These pH‐sensitive micelles with significant efficiency for intracellular drug release will be beneficial to the future of in vivo biomedical applications. © 2014 Society of Chemical Industry     

pH响应型mPEG-PCL嵌段共聚物胶束用作药物运输

该文合成了一种具有pH敏感性,较低毒性的两亲性嵌段共聚物以用于药物运输。聚乙二醇-聚己内酯(mPEG-PCL)是以聚乙二醇单甲醚为引发剂,开环己内酯聚合而成,阿霉素则是通过顺乌头酸裂解键连在聚己内酯的末端。该嵌段聚合物通过核磁共振、红外光谱等进行表征。共轭阿霉素后的嵌段聚合物在水溶液中能够自组装形成胶束,胶束粒径约为45.4 nm,透射电镜显示胶束具有近似的球形结构。阿霉素在pH=4.0下的释放速率明显快于pH=7.4下的释放速率。mPEG-PCL在细胞培养中无细胞毒性,包载阿霉素的胶束在人类MCF-7乳腺癌细胞上表现出迟缓的细胞毒性。通过共聚焦显微镜观察游离阿霉素和mPEG-PCL-DOX胶束在MCF-7细胞内的定位说明载体能够携带阿霉素进入细胞。     

Acid and light dual- stimuli-cleavable polymeric micelles

In this study, acid and light dual- stimuli-responsive amphiphilic AB-type methoxy poly(ethylene glycol)-acetal-ONB-poly(4-substituted-ε-caprolactone) (MPEG-a-ONB-PXCL) diblock copolymers were synthesized using ring-opening polymerization and nucleophilic substitution reactions. The prepared copolymer features an acid-cleavable acetal group and photocleavable o-nitrobenzyl linkage between the hydrophilic MPEG and hydrophobic PXCL blocks. The design enables the diblock copolymers to respond to both acid and ultraviolet (UV) light while ensuring the minimum number of stimuli-reactive moieties in the copolymer structure. The disruption of the copolymeric micelles in aqueous solution was examined under the action of pH or UV light alone or under the combined stimulation pH and UV light. Under the combined stimulation of UV irradiation and pH, the micellar nanoparticles could dissociate; therefore, the loaded molecules could be released from the assemblies more efficiently than under either stimulus alone. The nanoparticles exhibited nonsignificant toxicity against human cervical cancer (HeLa) cells at concentrations ≤300 μg mL^?1. Doxorubicin (DOX)-loaded micelles facilitated the uptake of DOX by the HeLa cells at the initial stage. The dual stimuli-cleavable polymeric micelles show promising potential as new nanocarrier for precisely controlled release of encapsulated drug.     

Synthesis and characterization of PEG–PCL–PEG triblock copolymers as carriers of doxorubicin for the treatment of breast cancer

Triblock copolymers of monomethoxy poly(ethylene glycol) (mPEG) and ε‐caprolactone (CL) were prepared with varying lengths of poly(ε‐caprolactone) (PCL) compositions and a fixed length of mPEG segment. The molecular characteristics of triblock copolymers were characterized by ¹H NMR, gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), and differential scanning calorimetry (DSC). These amphiphilic linear copolymers based on PCL hydrophobic chain and hydrophilic mPEG ending, which can self‐assemble into nanoscopic micelles with their hydrophobic cores, encapsulated doxorubicin (DOX) in an aqueous solution. The particle size of prepared micelles was around 40–92 nm. The DOX loading content and DOX loading efficiency were from 3.7–7.4% to 26–49%, respectively. DOX‐released profile was pH‐dependent and faster at pH 5.4 than pH 7.4. Additionally, the cytotoxicity of DOX‐loaded micelles was found to be similar with free DOX in drug‐resistant cells (MCF‐7/adr). The great amounts of DOX and fast uptake accumulated into the MCF‐7/adr cells from DOX‐loaded micelles suggest a potential application in cancer chemotherapy. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Biodegradable depsipeptide–PDO–PEG-based block copolymer micelles as nanocarriers for controlled release of doxorubicin

Nowadays, biodegradable amphiphilic block copolymers with stable performance and adjustable structure have attracted the interests of researchers in the field of drug delivery. In this work, the triblock copolymer, P(SBMD-co-PDO)-b-PEG-b-P(SBMD-co-PDO), was successfully synthesized by ring-opening polymerization of 3(S)-sec-butyl-morpholine-2,5-dione (SBMD) and p-dioxanone (PDO) with poly(ethylene glycol) (PEG) as the initiator. In phosphate buffered solution (PBS), these copolymers could self-assemble into nano-sized micelles that have a hydrophobic P(SBMD-co-PDO) core surrounded by a hydrophilic PEG shell. Because of the strong hydrogen bonding and hydrophobic interactions, doxorubicin (DOX) was loaded into the micelles with high loading capacity (LC, up to 28.4%) and encapsulation efficiency (EE, up to 62.5%). The drug-loaded micelles showed sustained-release of DOX along with the hydrolytic degradation of the micelles in PBS. Therefore, these amphiphilic triblock copolymers have potential as drug matrix for controlled release.     

ABC block copolymer as “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs

Amphiphilic triblock copolymer of poly(ethylene glycol)-block-poly(dimethylaminoethyl methacrylate)-block-poly(ε-caprolatone) (PEG-PDMA-PCL) was synthesized using a one-pot sequential oxyanionic polymerization of DMA and ε-CL, associated with a PEG-O⁻K⁺ macroinitiator. The pH-responsive micellization behavior of the copolymer was studied using dynamic light scattering (DLS), steady-state fluorescence and TEM techniques. The anti-cancer drug of doxorubicin (DOX) was chosen as a model drug to investigate the potential application of this triblock copolymer in drug controlled release. The results indicated the important roles of the PCL block for drug loading, the PDMA block for pH-responsive release, and PEG block for good bio-affinity. Cell cytotoxicity tests showed that the DOX-loaded PEG-PDMA-PCL micelles were pharmaceutically active to suppress the growth of SKOV-3 cells. This novel stimuli-responsive block copolymer is an attractive candidate as the “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs.     

Self-assembled polymeric micelles based on THP and THF linkage for pH-responsive drug delivery

Developing smart nanocarriers for drug delivery system is advantageous for many kinds of successful biomedicinal therapy. In this study, we designed an amphiphilic block copolymers containing pH-responsive tetrahydropyran (THP) and tetrahydrofuran (THF) linkage. Their structures were confirmed by ¹H NMR and gel permeation chromatography (GPC). The release rate of encapsulated drugs depends upon the pH value and pH sensitive linkage in the backbone of copolymers. For PLA–THP–PEG micelles the cumulative release amount of doxorubicin (DOX) was 62% at pH 5.0, which is about four times higher than that at pH 7.4. Under the same conditions the release rate for PLA–THF–PEG micelles is a little faster than that of the PLA–THP–PEG micelles. Cellular uptake study demonstrates that DOX-loaded micelles can easily enter the cells and produce the desired pharmacological action and minimizing the side effect of free DOX. These findings indicate that THP and THF linked diblock copolymer micelles is a promising candidate for drug carrier.     

Structure–property relationship of pH‐sensitive (PCL)2(PDEA‐b‐PPEGMA)2 micelles: Experiment and DPD simulation

The experiment and dissipative particle dynamics simulation were carried out on four polymers with different block ratios for the investigation of the structure–property relationship of (poly(ε‐caprolactone)₂‐[poly(2‐(diethylamino)ethyl methacrylate)‐b‐poly(poly(ethylene glycol) methyl ether methacrylate)]₂ [(PCL)₂(PDEA‐b‐PPEGMA)₂] micelles. The miktoarm star polymers assembled into spherical micelles composed of PCL core, pH‐sensitive PDEA mesosphere and poly (ethylene glycol) methyl ether methacrylate (PPEGMA) shell. When decreasing pH from 7.4 to 5.0, the hydrodynamic diameter and transmittance of (PCL)₂(PDEA‐b‐PPEGMA)₂ micelles increased along with globule‐uneven‐extended conformational transitions, owing to the protonation of tertiary amine groups of DEA at lower pH conditions. Doxorubicin (DOX) was mainly loaded in the pH‐sensitive layer, and more DOX were loaded in the core when increasing drug concentrations. The in vitro DOX release from the micelles was significantly accelerated by decreasing pH from 7.4 to 5.0. The results demonstrated that the pH‐sensitive micelles could be used as an efficient carrier for hydrophobic anticancer drugs, achieving controlled and sustained drug release. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3634–3646, 2014     

Fabrication of micelles from poly(butylene succinate) and poly(2‐methacryloyloxyethyl phosphorylcholine) copolymers as a potential drug carrier

A series of copolymers of poly(2‐methacryloyloxyethyl phosphorylcholine)‐b‐poly(butylene succinate)‐b‐poly(2‐methacryloyloxyethyl phosphorylcholine) (PMPC‐b‐PBS‐b‐PMPC) were synthesized by atom transfer radical polymerization. The structure of the polymers was characterized by ¹H NMR and infrared spectroscopy, and their thermal properties were described using TGA and DSC. In aqueous solutions, the PMPC‐b‐PBS‐b‐PMPC could form micelles with sizes ranging from 108 to 170 nm. In vitro release studies showed that acidic media and a longer PMPC chain benefited doxorubicin (DOX) release. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicated that the micelles had low cytotoxicity to HeLa and L929 cells. DOX‐loaded micelles exhibited high cytotoxicity to HeLa cells. Flow cytometry results demonstrated that DOX‐loaded micelles could be internalized by HeLa cells. The in vitro phagocytosis results showed 3.9‐fold and 5.5‐fold reductions compared with poly(lactic acid) (PLA) nanoparticles and PDS55 micelles. These results demonstrate that PMPC‐b‐PBS‐b‐PMPC block copolymer micelles have great promise for cancer therapy. © 2017 Society of Chemical Industry     

Core/shell pH‐sensitive micelles self‐assembled from cholesterol conjugated oligopeptides for anticancer drug delivery

A doxorubicin (DOX) delivery system of pH‐sensitive micelles self‐assembled from cholesterol conjugated His₅Arg₁₀ (HR15‐Chol) and His₁₀Arg₁₀ (HR20‐Chol) has been described in this article. The amphiphilic molecules have low critical micelle concentrations of 17.8 and 28.2 μg/mL for HR15‐Chol and HR20‐Chol, respectively, even at a low pH of 5.0. The pH‐sensitive histidine segment of the polypeptide block is insoluble at pH 7.4 but becomes positively charged and soluble via protonation at pH lower than 6.0. The size and zeta potential of DOX‐loaded micelles increases with the decrease in pH. Coarse‐grained simulations were performed to verify the structure of DOX‐loaded micelles and pH sensitivity of HR15/20‐Chol. The in vitro DOX release from the micelles is significantly accelerated by decreasing pH from 7.4 to 5.0. Furthermore, DOX release from the micelles is controlled by a Fickian diffusion mechanism. These micelles have great potential applications in delivering hydrophobic anticancer drugs for improved cancer therapy. © 2009 American Institute of Chemical Engineers AIChE J, 2010     

Bioinspired photo-degradable amphiphilic hyperbranched poly(amino ester)s: Facile synthesis and intracellular drug delivery

A novel amphiphilic photo-degradable hyperbranched polymer was reported at the first time. The hyperbranched o-nitrobenzyl containing poly(amino ester)s (HPAE) were prepared by one-pot Michael addition polymerization. The photo-induced degradation of hyperbranched poly(amino ester)s was confirmed by gel permeation chromatography (GPC) and UV-vis spectra. Bioinspired phosphorylcholine grafted HPAE (HPAE-PC) was synthesized via thiol-ene click chemistry. HPAE-PC can self-assemble to micelles and the micelles could be disassembled under UV irradiation because of the photo-degradation of HPAE. HPAE-PC micelles were used to load anticancer drug Doxorubicin (DOX). In vitro drug release studies showed that the release of DOX was much faster in the presence of UV irradiation than that without UV irradiation. The fluorescence microscope results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Moreover, the DOX-loaded HPAE-PC micelles under UV irradiation exhibited better anticancer activity against A549 cells than that of the nonirradiated ones. The novel amphiphilic photo-degradable hyperbranched polymers can be used to construct spatiotemporal on-demand drug delivery system for cancer therapy.     

Effect of graphene oxide on the pH-responsive drug release from supramolecular hydrogels

Polypseudorotaxane (PPR) hydrogels formed by inclusion complexes between poly(ethylene glycol) (PEG) and α-cyclodextrin (α-CD) are highlighted as promising biomaterial for drug delivery. Here, we report a novel injectable PPR hydrogel containing graphene oxide (GO) for pH-responsive controlled release of doxorubicin hydrochloride (DOX). Our results showed that the gelation rates of the PEG/α-CD supramolecular structures could be tailored depending on the reagent concentrations. The formation of PEG/α-CD inclusion complexes was confirmed by TEM and XRD, the latter further confirming that GO restricts their formation. The supramolecular hydrogels were easily loaded with DOX by simple addition into the PEG solution before the complex formation with the α-CD solution. Noteworthy, disruption of ionic interactions between DOX and GO in the nanocomposite at pH = 5.5 resulted in higher DOX release than under physiological conditions (pH = 7.4). This pH dependence was barely observed in pure PPR hydrogel. These findings introduce DOX-loaded supramolecular hydrogels nanocomposites as promising carriers for pH-responsive and therefore localized, drug delivery systems.     

Preparation of new dendrimer‐like star‐shaped amphiphilic poly(ethylene glycol)–poly(ϵ‐caprolactone) copolymers for biocompatible and high‐efficiency curcumin delivery

Novel amphiphilic star‐shaped terpolymers comprised of hydrophobic poly(?‐caprolactone), pH‐sensitive polyaminoester block and hydrophilic poly(ethylene glycol) (M_n = 1100, 2000 g mol^?1) were synthesized using symmetric pentaerythritol as the core initiator for ring‐opening polymerization (ROP) reaction of ?‐caprolactone functionalized with amino ester dendrimer structure at all chain ends. Subsequently, a second ROP reaction was performed by means of four‐arm star‐shaped poly(?‐caprolactone) macromer with eight ‐OH end groups as the macro‐initiator followed by the attachment of a poly(ethylene glycol) block at the end of each chain via a macromolecular coupling reaction. The molecular structures were verified using Fourier transform infrared and ¹H NMR spectroscopies and gel permeation chromatography. The terpolymers easily formed core–shell structural nanoparticles as micelles in aqueous solution which enhanced drug solubility. The hydrodynamic diameter of these agglomerates was found to be 91–104 nm, as measured using dynamic light scattering. The hydrophobic anticancer drug curcumin was loaded effectively into the polymeric micelles. The drug‐loaded nanoparticles were characterized for drug loading content, encapsulation efficiency, drug–polymer interaction and in vitro drug release profiles. Drug release studies showed an initial burst followed by a sustained release of the entrapped drug over a period of 7days at pH = 7.4 and 5.5. The release behaviours from the obtained drug‐loaded nanoparticles indicated that the rate of drug release could be effectively controlled by pH value. Altogether, these results demonstrate that the designed nanoparticles have great potential as hydrophobic drug delivery carriers for cancer therapy. © 2015 Society of Chemical Industry     

pH-responsive micelles based on (PCL)2(PDEA-b-PPEGMA)2 miktoarm polymer: controlled synthesis,characterization, and application as anticancer drug carrier

Amphiphilic A₂(BC)₂ miktoarm star polymers [poly(ϵ-caprolactone)]₂-[poly(2-(diethylamino)ethyl methacrylate)-b- poly(poly(ethylene glycol) methyl ether methacrylate)]₂ [(PCL)₂(PDEA-b-PPEGMA)₂] were developed by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The critical micelle concentration (CMC) values were extremely low (0.0024 to 0.0043 mg/mL), depending on the architecture of the polymers. The self-assembled empty and doxorubicin (DOX)-loaded micelles were spherical in morphologies, and the average sizes were about 63 and 110 nm. The release of DOX at pH 5.0 was much faster than that at pH 6.5 and pH 7.4. Moreover, DOX-loaded micelles could effectively inhibit the growth of cancer cells HepG2 with IC₅₀ of 2.0 μg/mL. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles. Therefore, the pH-sensitive (PCL)₂(PDEA-b-PPEGMA)₂ micelles could be a prospective candidate as anticancer drug carrier for hydrophobic drugs with sustained release behavior.     

Synthesis and self-assembly of amphiphilic poly(acrylic acid-b-dl-lactide) to form micelles for pH-responsive drug delivery

An amphiphilic diblock copolymer of poly(acrylic acid-b-dl-lactide) (PAAc-b-PDLLA) was synthesized by ring-opening polymerization of dl-lactide initiated by hydroxyl-terminated polyacrylic acid (PAAc-OH). The critical micelle concentration (CMC) of PAAc-b-PDLLA in aqueous solution, determined by fluorescence spectroscopy using pyrene as a probe, was found about 80 mg L⁻¹. A solution of PAAc-b-PDLLA in tetrahydrofuran (THF) was dialyzed against pure water to form pH-responsive micelles. Transmission electron microscopy (TEM) measurement showed that the micelles exhibited regular spherical morphology and the diameters of particles were in the range from 40 to 90 nm. The micelles were stable at a pH above 3 or at an ionic strength below 1.0, however, they aggregated and precipitated in the solutions when further decreasing pH or increasing ionic strength. Prednisone acetate, as a model hydrophobic drug, was loaded into the polymeric micelles. In vitro release of prednisone acetate from polymeric micelles showed that the release kinetics was strongly pH-dependent. Hydrophobic drug displayed “burst” release at pH 7.4, while only a small part of loaded drug released at pH 1.4. This provides a new choice to design delivery system for the gastrointestinal tract (GI tract), where the pH environment is strongly acidic in stomach and basic in intestine. The cytotoxicity measurement by MTT assay indicated that PAAc-b-PDLLA was low toxic in HeLa cells with an IC50 value of 2.8 mg mL⁻¹, which suggests that PAAc-b-PDLLA could be used as a safe candidate for pH-responsive drug delivery.     

Temperature,pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for controlled release

Temperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for drug delivery and release are designed. The well‐defined tetrablock copolymer poly(polyethylene glycol methacrylate)–poly[2‐(dimethylamino) ethyl methacrylate]–poly(N‐isopropylacrylamide)–poly(methylacrylic acid) (PPEGMA‐PDMAEMA‐PNIPAM‐PMAA) is synthesized via atom transfer radical polymerization, click chemistry, and esterolysis reaction. The tetrablock copolymer self‐assembles into noncrosslinked micelles in acidic aqueous solution. The core‐crosslinked micelles, shell‐crosslinked micelles, and shell–core dilayer‐crosslinked micelles are prepared via quaternization reaction or carbodiimide chemistry reaction. The crosslinked micelles are used as drug carriers to load doxorubicin (DOX), and the drug encapsulation efficiency with 20% feed ratio reached 59.2%, 73.1%, and 86.1%, respectively. The cumulative release rate of DOX is accelerated by single or combined stimulations. The MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay verifies that the inner‐layer crosslinked micelles show excellent cytocompatibility, and DOX‐loaded micelles exhibit significantly higher inhibition for HepG2 cell proliferation. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46714.     

Thermal modulation of intracellular drug distribution using thermoresponsive polymeric micelles

Intracellular distribution of free doxorubicin (DOX) or DOX-loaded in polymeric micelles with thermoresponsive outer shells of poly(N-isopropylacrylamide) or its copolymers in cultured human breast cancer cells (MCF-7) were investigated by fluorescence and confocal laser scanning microscopy. Free DOX accumulated rapidly and selectively in cell nuclei, independent of temperature changes. In contrast to free drugs, the intracellular distribution of DOX-loaded in the thermoresponsive polymeric micelles was significantly affected by temperature changes across lower critical solution temperature (LCST) of the micelles. Above the micelle LCST, DOX delivered by the micelles was localized uniformly inside of MCF-7 cells. By contrast, the amount of DOX delivered to MCF-7 cells drastically decreased below the micelle LCST due to minimal interaction of the micelles with cell membrane surfaces. These results clearly showed that the mechanism of the intracellular drug localization was different between free drugs and DOX-loaded in the micelles. The thermoresponsive micelles aggressively interacted with the cells and carried DOX into the cells via triggered phase transition of the outer shells. In addition, much lower accumulation of free DOX was observed in the resistant cells compared to its parent sensitive MCF-7 due to the resistant mechanism. Of interest, DOX accumulation in the resistant cells was almost in the same level as with MCF-7 (sensitive) cells for the micelle system above the LCST.     

pH-responsive magnetic mesoporous silica nanospheres for magnetic resonance imaging and drug delivery

Multi-functional magnetic mesoporous silica nanospheres (MMSNs), which were coated with poly(acrylic acid) (PAA), have been synthesized using the atom transfer radical polymerization of tert-butyl acrylate on the surface of MMSNs followed by the hydrolysis of the grafted poly(tert-butyl acrylate) chains. The resulting MMSN-PAA nanocomposites exhibit negligible cytotoxicity toward HeLa and L02 cells. Magnetic resonance imaging (MRI) studies reveal that the nanocomposites can be effectively taken-up by the cancer cells. The anticancer drug doxorubicin hydrochloride (DOX) can be loaded into the nanocomposites and subsequently released in a sustained and pH-responsive way because of the presence of pH-sensitive polymer shells. The DOX-loaded nanocomposites exhibit notable cytotoxicity to HeLa cancer cells. These results demonstrate that the pH-responsive MMSN-PAA nanocomposites can be applied to biological systems for MRI and drug delivery.     

枝化-环化结构共聚物用于酸响应载药体系

将溴代聚乙二醇(PEG2000Br)和缩醛化物二(2-丙烯酰氧基乙氧基)-(4-甲氧基苯基)甲烷(ACD)分别作为引发剂和单体,采用逆向增强原子转移自由基聚合(DE-ATRP)法得到嵌段共聚物聚乙二醇-b-聚[二(2-丙烯酰氧基乙氧基)-(4-甲氧基苯基)甲烷](PEG-b-PACDs)。通过核磁共振氢谱和凝胶渗透色谱表征了该聚合物的结构;用动态光散射和透射电镜表征了胶束的尺寸和形貌。结果表明,聚合物呈现枝化-环化结构,空白胶束的尺寸在70 nm左右,载药胶束尺寸在90 nm左右,胶束的药物包封率为48.7%。在pH为7.4时透析48 h后,药物释放率只有32.5%,在pH为5.4时透析48 h后,药物释放率为68.3%,表明共聚物在酸性条件下具有良好的药物缓释性。