查找使用阿拉丁产品的科研文献

Acid-triggered drug release from micelles based on amphiphilic oligo(ethylene glycol)–doxorubicin alternative copolymers

Ying Wang,Qiaojie Luo,Rui Sun,Guangyu Zha,Xiaodong Li,Zhiquan Shen,Weipu Zhu

We report a facile strategy to synthesize pH-sensitive amphiphilic oligo(ethylene glycol) (OEG)–doxorubicin (DOX) alternative conjugates. Poly[oligo(ethylene glycol) malicate] (POEGM) with numerous pendent hydroxyl groups was first synthesized by the direct polycondensation of oligo(ethylene glycol) (OEG) with malic acid under mild conditions. Then, benzaldehyde groups were introduced into the POEGM backbone via esterification between the pendant hydroxyl groups and 4-formylbenzoic acid. DOX moieties were finally attached to the polymeric backbone via benzoic imine linkages to obtain the OEG–DOX conjugates. Because of the high molecular weight and alternate architecture, this type of amphiphilic OEG–DOX alternative conjugates can form stable micelles in aqueous solution with a high DOX loading content (38.2 wt%) and low critical micelle concentrations (0.021 mg mL−1). Due to the pH-sensitive benzoic imine linkages between the DOX moieties and polymeric backbone, DOX could be rapidly released from the micelles at pH 5.8, whereas only a minimal amount of DOX was released at pH 7.4 under the same conditions. The cytotoxicity assay indicates that the OEG–DOX conjugates show cytotoxic effects to MCF-7 tumor cells, while the corresponding polymer material POEGM–CHO exhibits a great biocompatibility for MCF-7 tumor cells. These pH-sensitive and high drug loading nano-carriers based on the OEG–DOX alternative conjugates provide a promising platform for targeted cancer therapy.

Redox-mediated dissociation of PEG–polypeptide-based micelles for on-demand release of anticancer drugs

Huiyun Wen,Haiqing Dong,Jie Liu,Aijun Shen,Yongyong Li,Donglu Shi

Intelligent nanoparticles are capable of prolonged blood circulation without leakage of the payload and fast drug release upon exposure to environmental stimuli, such as redox stimuli, and therefore are highly desirable for cancer therapy. In this study, polymeric micelles were designed and developed with a hydrophilic poly(ethylene glycol) (PEG) shell and a hydrophobic poly-L-phenylalanine (PPhe) core, linked by a redox cleavable bond, i.e. mPEG-SS-PPhe. The mPEG-SS-PPhe micelles were loaded with the anticancer drug doxorubicin (DOX) and shown an on-demand release profile in the presence of redox agents such as glutathione (GSH). Remarkably, the GSH-triggered micellar dissociation accelerated in vitro release of DOX 4.87 fold faster at 10 mM GSH than that without GSH at 12 h. An enhanced inhibitory effect of DOX-loaded mPEG-SS-PPhe micelles was achieved by improving the intracellular GSH levels. Confocal laser scanning microscopy and flow cytometric analyses of HeLa cells further confirmed that DOX accumulation was accelerated by elevating the extracellular GSH concentrations. In addition, mPEG-SS-PPhe micelles showed excellent biocompatibility on L929 and HeLa cell lines. These redox-sensitive polymeric micelles may provide more possibilities as promising carriers for on-demand drug release in a controlled manner.

Multi-kinetic analysis reveals drug release and structural dissociation behaviors of paclitaxel-loaded polymeric micelles

Runtong Zhang,Mingyang Zhao,Yi Lu,Huiping Lu,Jingkai Gu,Jun He,Wei Wu

Polymeric micelles (PMs) may undergo structural dissociation with concurrent release and redistribution of payload and carrier material, processes that are difficult to resolve by conventional bulk pharmacokinetic analysis. Here, paclitaxel (PTX)-loaded methoxy poly(ethylene glycol)-poly(D,L-lactide) (mPEG-PLA) PMs were used to investigate the multi-kinetic interplay among drug payload, copolymer material, and PM particles during serum incubation and after intravenous administration. Serum was separated by gradient density ultracentrifugation (GDUC) into lipoprotein-rich, PM-density, and lipoprotein-deficient serum (LPDS) fractions. PTX and mPEG-PLA in each fraction were quantified by LC–Q-TOF/MS, whereas PM particles in the validated PM-density fraction were assessed by ACQ1-based fluorescence bioimaging. During in vitro serum incubation, separated PMs largely maintained their initial PTX-to-micelle ratio; released PTX redistributed mainly to LPDS, while part of the mPEG-PLA shifted toward HDL and LPDS. After intravenous administration, the PTX-to-micelle ratio declined rapidly, whereas mPEG-PLA and PM-associated fluorescence persisted longer, revealing early drug–carrier uncoupling. These findings demonstrate that PTX release, carrier–material redistribution, and PM disposition are interconnected but asynchronous. Fraction-resolved integration of PTX pharmacokinetics, mPEG-PLA materiokinetics, and PM particokinetics provides mechanistic information beyond bulk pharmacokinetics or particle tracking alone and offers a practical framework for evaluating drug-loaded PM formulations. A refined gradient density ultracentrifugation strategy integrating LC–Q-TOF/MS and ACQ fluorescence imaging enables fraction-resolved analysis of paclitaxel, carrier material, and polymeric micelles. Comparative multi-kinetic analysis reveals distinct drug–carrier behaviors during serum incubation and systemic circulation, highlighting asynchronous drug release, carrier redistribution, and particle disposition. Download: Download high-res image (300KB) Download: Download full-size image

Effect of Hydrophobicity of Core on the Anticancer Efficiency of Micelles as Drug Delivery Carriers

Chun-Yang Sun,Yin-Chu Ma,Zi-Yang Cao,Dong-Dong Li,Feng Fan,Jun-Xia Wang,Wei Tao,Xian-Zhu Yang

Recently, micelles, which are self-assembled by amphiphilic copolymers, have attracted tremendous attention as promising drug delivery systems for cancer treatment. Thus, the hydrophobic core of the micelles, which could efficiently encapsulate small molecular drug, will play a significant role for the anticancer efficiency. Unfortunately, the effect of hydrophobicity of micellar core on its anticancer efficiency was rarely reported. Herein, the amphiphilic diblock polymers of poly(ethylene glycol) and polyphosphoester with different side groups (butyl, hexyl, octyl) were synthesized to tune the hydrophobicity of the micellar core. We found that the in vitro cytotoxicity of the DOX-loaded micelles decreased with the increasing hydrophobicity of micellar core due to the drug release rate. However, following systemic delivery, the DOX-loaded micelles with the most hydrophobic core exhibited the most significant inhibition of tumor growth in a MDA-MB-231 tumor model, indicating the importance of hydrophobicity of core on the antitumor efficacy of drug delivery systems.

Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy

Zhiqiang Ma,Pengwei Hu,Changyong Guo,Dan Wang,Xingjie Zhang,Min Chen,Qirong Wang,Miao Sun,Peiyu Zeng,Fengkun Lu,Linhong Sun,Lan She,Hongtao Zhang,Jianzhong Yao,Feng Yang

Anti-tumor efficacy of c(RGDfK)-decorated polypeptide-based micelles co-loaded with docetaxel and cisplatin

Wantong Song,Zhaohui Tang,Dawei Zhang,Ying Zhang,Haiyang Yu,Mingqiang Li,Shixian Lv,Hai Sun,Mingxiao Deng,Xuesi Chen

There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG- g -Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly( l -glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG- g -Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an α v β 3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.

Salt/pH dual-responsive supramolecular brush copolymer micelles with molecular recognition of nucleobases for drug delivery

Dali Wang,Xiuying Huan,Lijuan Zhu,Jinyao Liu,Feng Qiu,Deyue Yan,Xinyuan Zhu

A new type of salt/pH dual-responsive micelles based on supramolecular amphiphilic brush copolymers, poly(2-hydroxyethyl metharylate)-g-(poly(ε-caprolactone)-adenine:uracil-poly(ethylene glycol)) (PHEMA-g-(PCL-A:U-PEG)) was developed for the anticancer drug delivery owing to the fact that the tumor tissues show low pH and high salt concentration. The supramolecular structure of brush copolymer was confirmed by variable-temperature 1H NMR and Fourier transform infrared spectroscopy (FTIR). Doxorubicin (DOX) as a model anticancer drug was efficiently loaded into the supramolecular micelles (up to 70%) due to the compact structure of brush polymer. The cumulative release profile of the DOX-loaded micelles showed a low level of drug release (about 20 wt% in 25 h) at pH 7.4 with a low salt concentration, and was significantly accelerated at a lower pH (5.0) and a high salt concentration (over 70 wt% in 6 h), exhibiting an salt/pH dual-responsive controlled drug release capability. Methyl tetrazolium (MTT) assay showed that DOX-loaded micelles had high anticancer efficacy against Hela cancer cells and blank micelles had a very low cytotoxicity. These supramolecular brush copolymer micelles possess many favorable traits, such as low cytotoxicity and excellent biodegradability, adequate drug loading capacity, and rapid drug release in response to the intracellular level of pH and salt concentration, which endow them as a promise candidate for delivering anticancer drugs.

Improved oral bioavailability, cellular uptake, and cytotoxic activity of zingerone via nano-micelles drug delivery system

Zhumei Ge,Qilong Wang,Qin Zhu,Mukhtar Yusif,Jiangnan Yu,Ximing Xu

Herein, a nano-micelle drug delivery system was developed to orally improved zingerone’s bioavailability and its antitumor effect. Indeed, zingerone-loaded d-α-tocopheryl polyethylene glycol succinate micelles (ZTMs) were effectively prepared, characterised and assessed. The ZTMs had diameter, polydispersity index, and zeta potential of 50.62 ± 0.25 nm, 0.168 ± 0.006, and −28.07 ± 0.33 mV, respectively, coupled with a high entrapment efficiency (m/m, %) were 94.71 ± 2.02. The release rate of ZTMs in three media was significantly greater than that of free zingerone. Intriguingly, results obtained from pharmacokinetic studies showed that the oral bioavailability of the ZTMs was enhanced by 5.10 times in comparison with the free zingerone. Further, the half inhibitory concentration (IC50) of ZTMs and free zingerone was 7.56 μg/ml and 14.30 μg/ml, respectively, on HepG2 cells. Hence, ZTMs may be used as a potential approach to enrich the solubility, bioavailability, and concomitant anti-proliferative effect of zingerone in vitro.

Oxidation of Sodium Deoxycholate Catalyzed by Gold Nanoparticles and Chiral Recognition Performances of Bile Salt Micelles

Jing Wang,Xu Xu,Hao Chen,Shuai-Shuai Zhang,Yin-Xian Peng

Au nanoparticles (NPs) were prepared by UV light irradiation of a mixed solution of HAuCl4and sodium deoxycholate (NaDC) under alkaline condition, in which NaDC served as both reducing agent and capping agent. The reaction was monitored by circular dichroism (CD) spectra, and it was found that the formed gold NPs could catalyze the oxidation of NaDC. A CD signal at ~283 nm in the UV region was observed for the oxidation product of NaDC. The intensity of the CD signal of the oxidation product was enhanced gradually with the reaction time. Electrospray ionization (ESI) mass spectra and nuclear magnetic resonance (NMR) spectra were carried out to determine the chemical composition of the oxidation product, revealing that NaDC was selectively oxidized to sodium 3-keto-12-hydroxy-cholanate (3-KHC). The chiral discrimination abilities of the micelles of NaDC and its oxidation product, 3-KHC, were investigated by using chiral model moleculesR,S-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate (R,S-BNDHP). Compared with NaDC, the micelles of 3-KHC displayed higher binding ability to the chiral model molecules. In addition, the difference in binding affinity of 3-KHC micelles towardsR,S-isomer was observed, andS-isomer was shown to preferentially bind to the micelles.Keywords:noble metal nanoparticles;catalytical oxidation;chiral recognition;bile salts;supramolecular chemistry

Cryo-TEM and rheological study on shear-thickening wormlike micelles of zwitterionic/anionic (AHSB/SDS) surfactants

Shuo Lu,Qiliang Mei,Jiayi Chen,Zhe Wang,Wenhong Li,Chunyan Feng,Xuefeng Li,Jinfeng Dong

Hypothesis Shear-thickening micelles were mostly made of cationic surfactants , but shear-thickening was rarely reported in the zwitterionic/anionic surfactants. Since wormlike micelles were essential in shear-thickening systems, it should be common for the hybrid wormlike micelles formed by zwitterionic/anionic surfactants, and their fundamental features need to be clarified. Experiments The micellization of zwitterionic surfactant homologies alkyl dimethyl amidopropyl hydroxyl sulfobetaine (AHSB) and sodium dodecyl sulfate (SDS) in brine was studied, and various environmental factors were considered systematically. Light scattering, rheology, zeta potential , 1 H NMR and cryo-TEM techniques were employed to characterize the AHSB/SDS wormlike micelles. Findings AHSB/SDS hybrid wormlike micelles were formed in a wide x SDS region to endow them with apparent viscosities, in which the electrostatic and hydrophobic interactions between AHSB and SDS molecules were critical. AHSB with the longer tail, the higher c AHSB and c NaCl were advantageous to enhance the viscosity because of the longitudinal growth of wormlike micelles. The shear-thickening AHSB/SDS samples were commonly composed of unbranched wormlike micelles with various length, and the shear-induced alignment of wormlike micelles was the major cause as verified by cryo-TEM. Moreover, the quantitative relationships on the critical shear rate ɣ̇ c were established, and the activation energies were obtained from the temperature-dependent ɣ̇ c .

Investigation of the in vivo integrity of polymeric micelles via large Stokes shift fluorophore-based FRET

Houbing Zhang,Hongjun Li,Zhiting Cao,Jinzhi Du,Lifeng Yan,Jun Wang

Polymeric micelles hold great potential for anticancer drug delivery. Sufficient integrity of polymeric micelles after intravenous injection is critical for successful drug delivery to solid tumors , but accurate measurement of the in vivo micellar integrity remains challenging. Methods based on Förster resonance energy transfer (FRET) to monitor the in vivo micellar integrity are frequently used. However, the self-quenching effect of these FRET fluorophores used has been improperly ignored and has caused inaccurate measurements. Herein, we report a FRET-based approach using the large Stokes shift (LSS) fluorophores NBD-X and MS735 as the donor and acceptor, respectively, to investigate the integrity of polyethylene glycol- block -poly(ε-caprolactone) (PEG-PCL) micelles. We established a mathematical formula for the integrity calculation, and an in vitro verification experiment showed that the formula results exactly matched the simulated results. Our results demonstrated that PEG-PCL micelles gradually dissociated in blood circulation, but approximately 60% of the micelles in plasma remained intact 72 h after intravenous ( i.v. ) injection. This LSS fluorophore-based FRET approach can be used to accurately monitor the integrity of nanoparticles , and this study demonstrates that most of PEG-PCL micelles maintain their aggregation state during blood circulation for anticancer drug delivery.

Research on the Blocking Reaction Kinetics and Mechanism of Aqueous Polyurethane Micelles Blocked by 2,4,6-Trichlorophenol

Hongchuan Wu,Zhiguo Li,Long Bai,Libin Zhu,Jiyou Gu

The blocked terminal-isocyanate (NCO) aqueous polyurethane micelles were prepared by using the 2,6-hexamethylene diisocyanate (HDI), polyethylene glycol (PEG), dimethylol propionic acid (DMPA), and 2,4,6-trichlorophenol (TCP) as blocking agent. This paper was focused on the kinetics research of the TCP blocking terminal-NCO of pre-polymer, which occurred during the preparation process of TCP blocked aqueous polyurethane micelles. The kinetics parameters were obtained in the absence and presence of dibutyl tin dilaurate (DBTDL) as catalyst, respectively. Furthermore, the mechanism for TCP blocking terminal-NCO of pre-polymer was explored. The results showed that the blocking reaction was second order reaction, and the reaction activation energy was 43.890 KJ/mol without catalyst. In the presence of DBTDL, the blocking reaction activation energy was reduced to 34.412 KJ/mol, and the reaction rate was improved significantly. In addition, TCP blocking terminal-NCO of pre-polymer could be ascribed to the nucleophilic addition between nucleophilic phenolic hydroxyl of TCP and the carbon atom of -NCO group.