查找使用阿拉丁产品的科研文献

pH/Reduction Dual-Responsive Oxidized Alginate-Doxorubicin (mPEG-OAL-DOX/Cys) Prodrug Nanohydrogels: Effect of Complexation with Cyclodextrins

Tingting Zhou,Jiagen Li,Xu Jia,Xubo Zhao,Peng Liu

Novel biocompatible and biodegradable pH/reduction dual-responsive oxidized alginate-doxorubicin (mPEG-OAL-DOX/Cys) prodrug nanohydrogels were designed for tumor-specific intracellular triggered release of anticancer drug DOX by conjugating DOX via acid-labile Schiff base linkage into the PEGylated oxidized alginate (mPEG-OAL) cross-linked with bioreducible disulfide bond. The effect of the complexation with cyclodextrins (α-CD and β-CD) before or after the cross-linking of the mPEG-OAL on the DOX content and controlled release performance was investigated. It was found that the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(CD)-OAL-DOX/Cys, prepared by cross-linking of the mPEG-OAL after complexation with cyclodextrins, exhibited better pH/reduction dual-responsive controlled release performance than the mPEG-OAL-DOX/Cys(CD) ones prepared by cross-linking of the mPEG-OAL before complexation with cyclodextrins, owing to the supramolecular cross-linking of the adjacent pseudopolyrotaxanes. Especially for the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(α-CD)-OAL-DOX/Cys, DOX was released rapidly under lower pH media mimicking the tumor microenvironment and completely released within 48 h, while the premature leakage under the simulated physiological condition was ∼40%, without burst release in both cases. The cellular toxicity and uptake results demonstrated that the mPEG(α-CD)-OAL-DOX/Cys prodrug nanohydrogels possessed similar inhibition against cancer cell growth in comparison with the free DOX and enhanced drug intracellular accumulation.

Development of novel hydrogels based on Salecan and poly(N-isopropylacrylamide-co-methacrylic acid) for controlled doxorubicin release

Xiaoliang Qi,Wei Wei,Junjian Li,Gancheng Zuo,Xinyu Hu,Jianfa Zhang,Wei Dong

Salecan is a novel water-soluble extracellular polysaccharide composed of a linear repeating unit of 1-3-linked glucopyranosyl. Salecan is suitable for the preparation of hydrogels for biomedical applications due to its outstanding biological and physicochemical profiles. Here we designed a novel semi-interpenetrating polymer network (semi-IPN) hydrogel that incorporated the hydrophilic polysaccharide Salecan into a stimuli-responsive poly(N-isopropylacrylamide-co-methacrylic acid) (PNM) hydrogel matrix for controlled drug release. In this research, on one hand, Salecan modified the architecture and the pore size of the semi-IPN network. On the other hand, Salecan played a vital role in modulating water content and tuning the water release rate of the developing hydrogel, resulting in an adjustable release rate of the drugs. Doxorubicin (DOX), an anticancer drug, was loaded into the semi-IPN hydrogels as a model drug, and the in vitro release assay exhibited that the release rate was closely related to the content of introduced Salecan, as well as the environmental temperature and pH of the release media. Cytotoxicity experiments demonstrated that all blank semi-IPN hydrogels were non-toxic to HepG2 and A549 cells, while drug released from the DOX-loaded hydrogels could still exert its pharmacological activity and had the ability to kill these two cancer cells. Altogether, this work provides a way to synthesize a new type of hydrogel as general drug delivery vectors with a desired release rate.

Magnetic targeted drug delivery carriers encapsulated with pH-sensitive polymer: synthesis, characterization and in vitro doxorubicin release studies

Juan Wu,Yueqing Shen,Wei Jiang,Wei Jiang,Yewen Shen

Nanomicelles based on a boronate ester-linked diblock copolymer as the carrier of doxorubicin with enhanced cellular uptake

Yan Xu,Yuanyuan Lu,Lei Wang,Wei Lu,Jin Huang,Ben Muir,Jiahui Yu

This study sought to develop a new type nanomicelle based on boronate ester-linked poly(ethylene glycol)- b -poly(benzyl glutamate) (PEG-BC-PBLG) diblock copolymer as the carrier of doxorubicin (Dox) to achieve acid-induced detachment of PEG shells and subsequent boronic acid-mediated enhanced endocytosis. In vitro studies revealed that the PEG-BC-PBLG copolymer was stable in neutral solutions but tend to hydrolysed under acidic conditions, which was attributed to the acid-sensitive properties of boronate ester bonds. The formation of PEG-BC@PBLG micelles was confirmed based on critical micelle concentration (CMC), particle size, and morphology observations. It was observed that these micelles were spherical with an average particle size of approximately 80   nm, as measured by dynamic laser scattering (DLS), suggesting their passive targeting to tumour tissue and endocytosis potential. Dox-loaded PEG-BC@PBLG micelles (PEG-BC@PBLG·Dox) showed sustained drug release profiles over 9   h, and their cumulative drug release was dependent on the pH value of the environment. Remarkably, cellular uptake ability of PEG-BC@PBLG micelles was found to be higher than that of non-boronate ester-linked PEG@PBLG micelles due to boronic acid-mediated endocytosis, as revealed by confocal laser scanning microscopy (CLSM) imaging of fluorescein isothiocyanate (FITC) green-conjugated micelles, thereby providing higher cytotoxicity against HepG2 cells. The antitumour activity and toxicity of PEG-BC@PBLG·Dox micelles in vivo were evaluated in BLAB/c mice against HepG2 cell-derived tumours. Compared with Dox, PEG-BC@PBLG·Dox showed reduced toxicity, whereas its tumour growth inhibition rate was 17% higher than that of free Dox. These results indicate the great potential of PEG-BC@PBLG micelles as the carrier of various lipophilic anticancer drugs with improved anti-tumour efficacy.

Redox/pH dual stimuli-responsive degradable Salecan-g-SS-poly(IA-co-HEMA) hydrogel for release of doxorubicin

Xinyu Hu,Yongmei Wang,Liangliang Zhang,Man Xu,Wei Dong,Jianfa Zhang

Salecan is a novel water-soluble extracellular β-glucan and possesses excellent physicochemical and biological properties. Here, redox/pH dual stimuli-responsive hydrogel based on Salecan grafted with itaconic acid (IA) and 2-hydroxyethyl methacrylate (HEMA) were prepared using disulfide-functionalized crosslinker N,N - bis (acryloyl)cystamine (BAC) for controlled drug delivery. The introduction of carboxylic groups endows the system with pH-sensitive character, swelling behavior of the hydrogel was conducted by changing the pH and Salecan content. It was demonstrated that DOX was efficiently loaded into the hydrogels and released in a controlled fashion via pH-control and swelling-shrinking mechanism. More importantly, DOX-loaded hydrogels showed dose dependent cytotoxicity toward A549 cell, and efficient cell killing was observed. Furthermore, a key point of this study was that the presence of disulfide linkage in system favored the degradation of hydrogels in the reductive environment. These results highlight the potential of Salecan- g -SS-poly(IA- co -HEMA) hydrogel as a novel system for the controlled release of anti-cancer drugs.

Synthesis and characterization of mesoporous magnetic nanocomposites wrapped with chitosan gatekeepers for pH-sensitive controlled release of doxorubicin

Juan Wu,Wei Jiang,Yewen Shen,Wei Jiang,Renbing Tian

Multifunctional nanocarriers based on the Fe 3 O 4 nanoparticles core and mesoporous silica shell (mSiO 2 ) were synthesized for controlled drug release through magnetic targeting and pH-sensitive performances. The developed Fe 3 O 4 @mSiO 2 nanocarriers exhibited a suitable size (63   nm) and good magnetic responsibility, doxorubicin (DOX) could be successfully loaded into the mesoporous of Fe 3 O 4 @mSiO 2 via electrostatic interaction, and the drug loading content and loading efficiency are 29.3% and 93.6%, respectively. The chitosan (CS) was employed to wrap the Fe 3 O 4 @mSiO 2 -DOX as the blocking agent to inhibit premature drug release, and the final CS/Fe 3 O 4 @mSiO 2 -DOX exhibited excellent pH-sensitivity, 86.1% DOX was released within 48   h at pH   4.0. Furthermore, all the release behaviors fit the Higuchi model very well and a purely diffusion-controlled process played a major role on DOX release from CS/Fe 3 O 4 @mSiO 2 -DOX. In addition, MTT assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the CS/Fe 3 O 4 @mSiO 2 -DOX had high anti-tumor activity, while the Fe 3 O 4 @mSiO 2 nanocarriers were practically non-toxic. Thus, our results revealed that the CS/Fe 3 O 4 @mSiO 2 -DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy.

Reduction-sensitive micelles self-assembled from amphiphilic chondroitin sulfate A-deoxycholic acid conjugate for triggered release of doxorubicin

Hongxia Liu,Shuqin Wu,Jingmou Yu,Dun Fan,Jin Ren,Lei Zhang,Jianguo Zhao

Reduction-sensitive chondroitin sulfate A (CSA)-based micelles were developed. CSA was conjugated with deoxycholic acid (DOCA) via a disulfide linkage. The bioreducible conjugate (CSA-ss-DOCA) can form self-assembled micelles in aqueous medium. The critical micelle concentration (CMC) of CSA-ss-DOCA conjugate is 0.047   mg/mL, and its mean diameter is 387   nm. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the micelles with high loading efficiency. Reduction-sensitive micelles and reduction-insensitive control micelles displayed similar DOX release behavior in phosphate buffered saline (PBS, pH   7.4). Notably, DOX release from the reduction-sensitive micelles in vitro was accelerated in the presence of 20   mM glutathione-containing PBS environment. Moreover, DOX-loaded CSA-ss-DOCA (CSA-ss-DOCA/DOX) micelles exhibited intracellular reduction-responsive characteristics in human gastric cancer HGC-27 cells determined by confocal laser scanning microscopy (CLSM). Furthermore, CSA-ss-DOCA/DOX micelles demonstrated higher antitumor efficacy than reduction-insensitive control micelles in HGC-27 cells. These results suggested that reduction-sensitive CSA-ss-DOCA micelles had the potential as intracellular targeted carriers of anticancer drugs.

Biodegradable Polymersomes as Nanocarriers for Doxorubicin Hydrochloride: Enhanced Cytotoxicity in MCF-7/ADR Cells and Prolonged Blood Circulation

Chao Yanhui,Liang Yuheng,Fang Guihua,He Haibing,Yao Qing,Xu Hang,Chen Yinrong,Tang Xing

Purpose DOX is one of the most potent anticancer drugs. But its short half-life and the occurrence of multi-drug resistance (MDR) markedly limit its clinical application. To solve these problems, we develop DOX loaded polymersomes (DOX polymersomes). Methods An methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone) (mPEG-b-PCL) copolymer was synthesized and used to prepare DOX polymersomes. The pharmaceutical properties of DOX polymersomes were characterized. The in vitro release profile of DOX from polymersomes was investigated. The in vitro cytotoxicity and cell uptake studies were performed on MCF-7 and MCF-7/ADR cells. The in vivo pharmacokinetic profiles were investigated on Sprague–Dawley rats. Results DOX polymersomes had a nano-scale particle size of about 60 nm with a hydrophobic membrane about 10 nm in thickness. Release of DOX from the polymersomes took place in a sustained manner. Cell experiments showed DOX polymersomes enhanced the cytotoxicity and the intracellular accumulation of DOX in MCF-7/ADR cells, compared with free DOX. In vivo pharmacokinetic study showed the DOX polymersomes increased the bioavailability and prolonged the circulation time in rats. Conclusions The entrapment of DOX in biodegradable polymersomes could enhance cytotoxicity in MCF-7/ADR cells and improve its in vivo pharmacokinetic profile.

Development of phosphonate-terminated magnetic mesoporous silica nanoparticles for pH-controlled release of doxorubicin and improved tumor accumulation

Erxi Che,Long Wan,Ying Zhang,Qinfu Zhao,Xiling Han,Jia Li,Jia Liu,Siling Wang

In this study, phosphonate-terminated magnetic mesoporous nanoparticles (pMMSNs) was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles (MSNs) and followed by grafting phosphonate group on to the surface of MMSNs. The carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer (VSM). pMMSNs had a spherical morphology and a pore size of 2.2 nm. From N 2 adsorption-desorption analysis, pMMSNs had a surface area of 613.4 m 2 /g and a pore volume of 0.78 cm 3 /g. Phosphonate modification improved the colloidal stability of MMSNs, and the hydrodynamic diameter of pMMSNs was around 175 nm. The hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from −19.3 mV to −28.8 mV pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of MMSNs. In addition, the rate and amount of release of doxorubicin (DOX) from DOX/pMMSNs was pH-dependent and increased with the decrease of pH. At pH 7.4, the release amount was quite low and only approximately 17 wt% of DOX was released in 48 h. At pH 5.0 and 3.0, the release rate increased significantly and the release amount achieved 31 wt% and 60 wt% in 48 h, respectively. To evaluate the magnetic targeting performance of pMMSNs, FITC labeled pMMSNs was injected into mice bearing S180 solid tumor. FITC labeled pMMSNs controlled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.

Development of Zwitterionic Polymer-Based Doxorubicin Conjugates: Tuning the Surface Charge To Prolong the Circulation and Reduce Toxicity

Zhen Wang,Guanglong Ma,Juan Zhang,Weifeng Lin,Fangqin Ji,Matthew T. Bernards,Shengfu Chen

Polymer–drug conjugates are commonly used as nano drug vehicles (NDVs) to delivery anticancer drugs. Zwitterionic polymers are ideal candidates to conjugate drugs because they show higher resistance to nonspecific protein adsorption in complex media than that of nonionic water-soluble polymers, such as poly(ethylene glycol). However, the charge balance characteristics of zwitterionic polymers used as NDVs will be broken from the inclusion of additional charged groups brought by conjugated drugs or functional groups, leading to the loss of resistance to protein adsorption. Consequently, the nonspecific protein adsorption on drug carriers will cause fast clearance from the blood system, an immune response, or even severe systemic toxicity. To overcome this drawback, a model zwitterionic polymer, poly(carboxybetaine methacrylate) (pCBMA), was modified by the introduction of a negatively charged component, to neutralize the positive charge provided by the model drug, doxorubicin (DOX). A DOX-conjugated NDV which possesses excellent resistance to nonspecific protein adsorption was achieved by the formation of a strongly hydrated pCBMA shell with a slightly negative surface charge. This kind of DOX-conjugated NDV exhibited reduced cytotoxicity and prolonged circulation time, and it accelerated DOX release under mild acid conditions. In tumor-bearing mouse studies a 55% tumor-inhibition rate was achieved without causing any body weight loss. These results indicate the importance of charge tuning in zwitterionic polymer-based NDVs.

Poly(methyl methacrylate)/poly(ethylene glycol)/poly(ethylene glycol dimethacrylate) micelles: Preparation, characterization, and application as doxorubicin carriers

Lili Yu,Lin Yao,Jing You,Yihui Guo,Liyan Yang

A crosslinked amphiphilic copolymer [poly(ethylene glycol) (PEG)–poly(methyl methacrylate) (PMMA)–ethylene glycol dimethacrylate (EGDM)] composed of PMMA, PEG, and crosslinking units (EGDM) was synthesized by atom transfer radical polymerization to develop micelles as carriers for hydrophobic drugs. By adjusting the molar ratio of methyl methacrylate and EGDM, three block copolymer samples (P0, P1, and P2) were prepared. The measurement of gel permeation chromatography and 1 H-NMR indicated the formation of crosslinked structures for P1 and P2. Fluorescence spectroscopy measurement indicated that PEG–PMMA–EGDM could self-assemble to form micelles, and the critical micelle concentration values of the crosslinked polymer were lower than those of linear ones. The prepared PEG–PMMA–EGDM micelles were used to load doxorubicin (DOX). The drug-loading efficiencies of P1 and P2 were higher than that of P0 because the crosslinking units enhanced the micelles' stability. With increasing drug-loading contents, DOX release from the micelles in vitro was decreased, and in the crosslinked formulations, the release rate was also slower. An in vitro release study indicated that DOX release from the micelles for the linear samples was faster than that for crosslinked micelles. The drug feeding amount increased and resulted in an increase in the drug-loading content, and the loading efficiency decreased. These PEG–PMMA–EGDM micelles did not show toxicity in vitro and could reduce the cytotoxicity of DOX in the micelles; this suggested that they are good candidates as stable drug carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 39623.

Cancer therapy and fluorescence imaging using the active release of doxorubicin from MSPs/Ni-LDH folate targeting nanoparticles

Dian Li,Yu-Ting Zhang,Meng Yu,Jia Guo,Deeptangshu Chaudhary,Chang-Chun Wang

Hierarchical structured nanomaterials with diverse functionality, such as magnetic susceptibility , stimuli-responsiveness, environmental sensing and biocompatibility, are highly sought after for biomedicine and biodetection alike. In this study, we designed and fabricated a new kind of multifunctional core/shell nanospheres as biodegradable targeted drug carriers, the controlled drug release progress and therapeutic effect were monitored in-situ by the fluorescent state of the cells. Firstly, the core/shell nanospheres with biodegradability were synthesized using magnetic supraparticles (MSPs) as core and the layered double hydroxide (LDH) as shell via a hydrothermal route, the reaction parameters were well investigated to obtain the desired structure of the LDH shell. The anti-cancer drug doxorubicin was modified with carboxyl group (DOX-COOH) and loaded in the shell of MSPs/LDH nanospheres via an anion-exchange intercalation. To endow the nanospheres with tumor-targeting capability, IDA (iminodiacetic acid)-modified folate was successfully immobilized onto the surface of LDH shell using chelating interaction. These nanospheres behaved as multifunctional carriers for targeted delivery of anti-cancer drug, doxorubicin (DOX), within Hela cells and thus, these nano-drugs exhibited clear cytotoxicity and inhibition toward Hela cells as compared to normal cell-lines of HEK 293T cells. Interestingly, after the internalization of these nano-drugs, there was a sharp contrast in illumination between the tumorous Hela cells and the normal HEK 293T cells, the acidic cytoplasm of Hela cell stimulated DOX-COOH in LDH shell quickly degraded into positive-charged DOX, and then rapidly escaped from the positive-charged intercalation of LDH shell by strong repulsive interaction, the released DOX rapidly lit up the whole tumor cells in a short time, but only very weak light was found in HEK 293T cells.