JOURNAL OF BIOMATERIALS APPLICATIONS
·
2021
·
IF 2.646
Qiang Li,Dongsheng Fu,Jie Zhang,Tianyang Li,Huifang Wang,Wenjuan Hou,Baolong Niu,Ruijie Guo,Yiming Liu
Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting dual-agent delivery nanoparticles were prepared, into which hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic curcumin (CUR) were entrapped. Tyrosine (Tyr) was grafted onto poly(aspartic acid) (PASP) to produce PASP-Tyr, the following reaction between hyaluronic acid (HA) and ethylenediamine (EDA) modified PASP-Tyr formed the nanocarrier HA-EDA-PASP-Tyr (HEPT), and the loading capacity was up to 50.9 ± 4.3% for CUR and 26.0 ± 1.9% for DOX. The spherical HEPT with the mean particle size of 142.9 ± 11.4 nm expanded and deformed into petaloid pattern with an increased size of about 2 µm when triggered by the acidic microenvironment. In vitro anticancer activity evaluation revealed that the co-loaded (DOX+CUR)@HEPT nanoparticles presented higher cytotoxicity against HCT-116 cells compared with that of the free combination of (DOX+CUR). Confocal laser scanning microscopy observation indicated that HEPT carrier promoted cellular uptake of drugs by means of active targeting capacity of HA ligand. With high loading capacity and tailored carrier structure, the nanoparticles formulations may offer a new strategy for cancer treatment.
研究领域:
药剂学
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肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 8
·3277-3286
·
IF 5.251
Jun Li,Zu-E. Hu,Xian-Ling Yang,Wan-Xia Wu,Xiu Xing,Bo Gu,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
Dual stimuli-responsive camptothecin polymeric prodrugs (CPT Prodrugs) with grafted structures were designed via chemoenzymatic methods and combined with doxorubicin (DOX) for synergistic drug delivery to improve anticancer efficiency. The CPT Prodrugs loaded DOX with a high efficiency through the cooperative contribution of several interaction forces. The produced amphiphilic polymeric prodrugs loaded with DOX, referred to as DOX@CPT Prodrugs, formed homogeneous spherical micelles of appropriate sizes (sub-50 nm). The DOX@CPT Prodrug micelles showed excellent stability in release experiments under in vitro physiological conditions and maintained over 80% drug loading after 4 weeks when stored at 4 °C. Under weakly acidic pH and reduced glutathione (GSH) conditions, the DOX@CPT Prodrugs with high disulfide and tertiary amine content achieved synergistic release of the two loaded drugs and biodegraded into low-molecular-weight compounds. The cell experiments confirmed that the internalization of DOX@CPT Prodrugs into cancer cells was greatly improved by nearly 30% compared with that of free drugs. Furthermore, the synergistic drug delivery system exhibited superior anticancer efficiency with highly improved cell selectivity ratios (up to 127.0%) and greatly enhanced synergistic effects (up to 23.9%) benefiting from good long-term stability, better internalization by cells and sensitive pH and GSH dual-responsivity. In addition, the DOX@CPT Prodrugs with suitable sizes and good water solubility also exhibited a greater penetrability in the case of simulating solid tumors than the free drugs. These results demonstrate the potential of DOX@CPT Prodrugs as biodegradable, dual-responsive combination therapy nanocarriers for synergistic anticancer treatment.
研究领域:
药学
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肿瘤学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Jiahui He,Wei Wang,Huicong Zhou,Pan She,Pantian Zhang,Yi Cao,Xuefei Zhang
A novel cytocompatible and pH-sensitive amphiphilic polymeric prodrug named as mPEG- b -norbornene functional PLA-graft-Doxorubicin (mPEG- b -PLA- g -DOX) was synthesized by ROP (ring-opening polymerization), then condensation and followed by click reaction. The polymeric carriers were grafted with triazo group. Doxorubicin (DOX) was modified by the cyclooctyne via condensation reaction and conjugated to the polymeric carriers through the SPAAC (Strain-Promoted Alkyne-Azide Cycloaddition) click reaction. There was a Schiff base between the DOX and cyclooctyne which could result in the pH stimuli-responsiveness for controlled release of anti-cancer drug. The resultant mPEG- b -PLA- g -DOX prodrug was characterized by the 1 H NMR, GPC and HPLC. The content of DOX in prodrug reached 17.4% as measured by the UV spectrum. The amphiphilic polymeric prodrug could self-assemble into micelle which was characterized by the dynamic light scattering (DLS) and scanning electron microscope (SEM). The profile of in vitro drug release exhibited enhanced drug release at acidic pH (pH = 5.3) compared with neutral pH (pH = 7.4). The results of MTT assay showed that the amount of DOX required for MCF-7 cells was reduced after DOX molecules were prepared into polymer prodrug, which was conducive to reducing side effects under the premise of ensuring inhibitory effect.
研究领域:
药学
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肿瘤学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Meijia Song,Yan Liang,Keke Li,Jing Zhang,Nan Zhang,Baocheng Tian,Jingtian Han
Tumor targeted drug delivery system has been developed as a promising approach to improve cancer chemotherapy . The design of hyaluronic acid (HA)-modified nanocarriers has been proven to be effective for targeting CD44 overexpressing tumor cells. Moreover, combination therapy can improve the therapeutic effect and delay the development of drug resistance. In this study, doxorubicin (DOX) and paclitaxel (PTX) co-loaded liposomal delivery system modified with an acid-cleavable cholesterol-HA conjugate (Chol-HA) was prepared by post-insertion method. The dual-drug co-loaded HA modified liposome (HA-D/P-Lip), had a suitable particle size of 125.5 ± 0.79 nm with negative surface charge of −9.56 ± 0.62 mV, and acceptable encapsulation efficacy of 93.6 ± 0.51% (DOX) and 70.4 ± 1.46% (PTX). In vitro drug release study showed that the cumulative release of both drugs over 72 h were much higher in pH 5.5 phosphate buffer than that in pH 7.4 phosphate buffer. In vitro cytotoxicity study against MCF-7 breast cancer cells illustrated superior cytotoxicity and obvious synergistic effect in comparison to free drug or single drug loaded liposome via MTT assay. In vitro cellular uptake study demonstrated a higher cell internalization of HA-DOX-Lip compared with DOX loaded non-modified liposome (DOX-Lip) and free DOX. Therefore, the pH-sensitive HA-targeted liposome may be a useful targeted nanocarrier for efficient tumor therapy.
研究领域:
肿瘤学
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药剂学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 8
·1709
·
IF 4.2
Yanru Hu,Peng Liu
The diselenide bond has attracted intense interest in redox-responsive drug delivery systems (DDSs) in tumor chemotherapy, due to its higher sensitivity than the most investigated bond, namely the disulfide bond. Here, a diselenide-bridged doxorubicin dimeric prodrug (D-DOXSeSe) was designed by coupling two doxorubicin molecules with a diselenodiacetic acid (DSeDAA) molecule via α-amidation, as a redox-triggered drug self-delivery system (DSDS) for tumor-specific chemotherapy. The drug release profiles indicated that the D-DOXSeSecould be cleaved to release the derivatives selenol (DOX-SeH) and seleninic acid (DOX-SeOOH) with the triggering of high GSH and H2O2, respectively, indicating the double-edged sword effect of the lower electronegativity of the selenide atom. The resultant solubility-controlled slow drug release performance makes it a promising candidate as a long-acting DSDS in future tumor chemotherapy. Moreover, the interaction between the conjugations in the design of self-immolation traceless linkers was also proposed for the first time as another key factor for a desired precise tumor-specific chemotherapy, besides the conjugations themselves.
研究领域:
药物化学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL RESEARCH
·
2017
·Vol. 34
·期 10
·2172-2184
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IF 3.002
Yin Xuelei,Chi Yingying,Guo Chuanyou,Feng Shuaishuai,Liu Jinhu,Sun Kaoxiang,Wu Zimei
Purpose To investigate the potential of a reduction-sensitive and fusogenic liposomes, enabled by surface-coating with chotooligosaccharides (COS) via a disulfide linker, for tumor-targeted cytoplasmic drug delivery. Methods COS (MW2000-5000) were chemically tethered onto the liposomes through a disulfide linker (-SS-) to cholesterol (Chol). Doxorubicin (DOX) was actively loaded in the liposomes. Their reduction-sensitivities, cellular uptake, cytotoxicity, pharmacokinetics and antitumor efficacy were investigated. Results The Chol-SS-COS/DOX liposomes (100 nm) had zeta potential of 33.9 mV and high drug loading (13% w /w). The liposomes were stable with minimal drug leakage under physiological conditions but destabilized in the presence of reducing agents, dithiothreitol (DTT) or glutathione (GSH) at 10 mM, the cytosolic level. MTT assay revealed that the cationic Chol-SS-COS/DOX liposomes had higher cytotoxicity to MG63-osteosarcoma cells than non-reduction sensitive liposome (Chol-COS/DOX). Flow cytometry and confocal microscopy revealed that Chol-SS-COS/DOX internalized more efficiently than Chol-COS/DOX with more content to cytoplasm whereas Chol-COS/DOX located around the cell membrane. Chol-SS-COS/DOX preferentially internalized into MG63 cancer cell over LO2 normal liver cells. In rats both liposomes produced a prolonged half-life of DOX by 4 - 5.5 fold ( p < 0.001) compared with the DOX solution. Chol-SS-COS/DOX exhibited strong inhibitory effect on tumor growth in MG63 cell-bearing nude mice ( n = 6), and extended animal survival rate. Conclusions Reduction-responsive Chol-SS-COS liposomes may be an excellent platform for cytoplasmic delivery of anticancer drugs. Conjugation of liposomes with COS enhanced tumor cell uptake, antitumor effect and survival rate in animal models.
研究领域:
药剂学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Tingxian Liu,Mingfang Wang,Tianqi Wang,Yao Yao,Na Zhang
The greatest challenge in combining chemotherapy and gene therapy is the construction of a suitable platform for the co-delivery of the drug and the therapeutic gene. In this study, a simplified and effective system for the co-loading and intracellular co-delivery of doxorubicin (Dox) and siRNA was developed. Oligodeoxynucleotides with CGA repeating units (CGA-ODNs) were introduced to load Dox. The loading mechanism was based on the ability of Dox to intercalate within double-stranded 5′-GC-3′ or 5′-CG-3′ sequences. Poly(ethyleneimine) (PEI) was used to condense siRNA and Dox loaded CGA-ODNs (CGA-ODNs-Dox) to obtain Dox and siRNA co-loaded nanocomplexes (PEI/CGA-ODNs-Dox&siRNA, PDR). The cellular uptake of PDR in A549 and HepG2 cells was 39.52% and 36.78%, respectively, indicating that the co-loading and co-delivery effect was achieved through the mono-loading method. An in vitro drug release study indicated that CMCS-poly(ethylene glycol) (PEG)-NGR (CPN) modified PDR (CPN-PDR) displayed a pH-triggered drug release property due to the reversed surface charge of CMCS in an acidic environment. Cellular uptake studies also confirmed that the disassembly of CPN-PDR was induced by an acidic pH in the extracellular matrix. Moreover, lysosomal escape of both Dox and siRNA was observed. Successful accumulation of Dox in the cell nucleus and siRNA in the cytoplasm was also demonstrated. Consequently, the novel construction of a simplified loading method and high co-delivery efficiency was proven to be a promising platform for the co-delivery of drug and siRNA.
研究领域:
药学
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分子生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2016
·
IF 0
Xia Dong,Chang Wei,Hongli Chen,Jingwen Qin,Jie Liang,Deling Kong,Tianjun Liu,Feng Lv
Real-time tracking of a drug delivery system and its therapeutic effects in vivo are crucial to designing a novel pharmaceutical system and revealing the mechanism of drug therapy. Multispectral fluorescence imaging can locate the drug and carrier simultaneously without interference. This advanced method enables the tracking of a drug delivery system. Herein, a doxorubicin (Dox) loaded zinc phthalocyanine incorporated hydrogel was developed as a dual fluorescent drug delivery system to monitor the release of the drug and the degradation of the carrier. An injectable thermosensitive hydrogel based on a four-arm poly(ethylene glycol) (PEG)–poly(ε-Caprolactone) (PCL) copolymer was prepared and characterized with a zinc phthalocyanine core as the drug carrier. The hydrogel degradation and drug delivery in vivo were tracked by a multispectral fluorescence imaging system in nude mice bearing hepatic tumors. Moreover, the real-time tumor inhibition progress was tracked in vivo for 18 days by bioluminescence imaging. A multispectral analysis can separate the fluorescence signals from the drug and carrier in the Dox loaded hydrogel and provide their location in the tumor tissue. The drug release and hydrogel degradation can be drastically tracked respectively without mutual interference. The fluorescence imaging results reveal improved tumor inhibitory effects of the Dox loaded hydrogel. Optical imaging allows for visible tracking of the entire drug delivery process. The Dox loaded phthalocyanine incorporated thermosensitive hydrogel is a potential visible drug delivery system for tumor therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
CELL PROLIFERATION
·
2018
·Vol. 51
·期 5
·e12488
·
IF 4.936
Tingting Kong,Liying Hao,Yuanyuan Wei,Xiaoxiao Cai,Bofeng Zhu
Objectives Carbon dots (CDs) are one of the most promising carbon-based materials in bioimaging and drug/gene delivery applications. In this study, we have attempted to study the drug carrying capacity of highly fluorescent CDs for delivery of doxorubicin (DOX) and investigate the therapeutic activity of the CDs-DOX drug delivery system. Materials and methods Carbon dots were synthesized by means of a hydrothermal approach with mixing citric acid and ethylenediamine. The properties of CDs were characterized in respects of spectral property, zeta potential, particle morphology and chemical composition. The drug loading efficiency (DLE) and release profile of CDs-DOX were determined by a fluorescence spectrophotometer. We investigated the cellular toxicity and pharmaceutical activity of CDs and CDs-DOX in L929 cells and MCF-7 cells by the CCK-8 assay. We also studied the cellular uptake of CDs-DOX with the methods of confocal microscopy and flow cytometry. In addition, the effect of CDs-DOX on cell apoptosis was assessed by flow cytometry. Results The obtained CDs possessed good biocompatibility and showed a potential capacity of promoting proliferation. DOX was successfully conjugated to CDs through electrostatic interaction, and the results of the DLE and loading content (DLC) suggested a relatively high drug loading capacity of CDs. Compared with free DOX, the CDs-DOX complex had a higher cellular uptake and better anti-tumour efficacy on MCF-7 cells. Conclusions The results of this study indicated that the CDs-DOX drug delivery system had a potential value in cancer chemotherapeutic application.
研究领域:
药学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Chaoping Fu,Hailiang Li,Nannan Li,Xiangwan Miao,Minqiang Xie,Wenjun Du,Li-Ming Zhang
A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by 1 H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition.
研究领域:
药剂学
·
肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Ying Wang,Feng Bai,Qiang Luo,Mingliang Wu,Gang Song,Hongmei Zhang,Jian Cao,Yanqing Wang
Lycium barbarum polysaccharide-doxorubicin (LBP-DOX) nanoparticles were synthesized via a one-step Schiff base reaction between oxidized Lycium barbarum polysaccharide (oxidized LBP) and doxorubicin (DOX). The structure of LBP-DOX nanoparticles was characterized by multi-spectral methods, 1 H nuclear magnetic resonance ( 1 H NMR), transmission electron microscopy (TEM), and thermo gravimetric analysis (TGA). The rheological properties of LBP-DOX nanoparticles were studied. With the increase of shear rate, the viscosity of LBP and LBP-DOX nanoparticles gradually decreases at 25 °C. Under the same strain, the storage modulus (G′) and loss modulus (G″) of LBP-DOX nanoparticles were inferior to LBP. The DOX release from LBP-DOX nanoparticles was pH-dependent and was accelerated by decreasing pH. Cytotoxicity study showed that the LBP-DOX nanoparticles have significantly enhanced cytotoxicity in vitro, especially for human Hepatic cancer cell line HepG2.
研究领域:
药学
·
肿瘤学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 112
·92292-92302
·
IF 3.84
Meng Cai,Mengyuan Ye,Xingxing Shang,Honghao Sun,Mingxing Liu,Hongmei Sun,Zhuo Ma,Hongda Zhu
Polymeric micelles as nanocarrier-based drug delivery systems provide an innovative platform for selectively delivering active molecules and offer better antitumour activity. However, circulation stability in vivo, controllable drug intracellular release and high targeting efficiency are several practical challenges for micelles. Therefore, we developed cRGD-modified and shell crosslinked micelles (RSCMs) based on amphiphilic poly(styrene-co-maleic anhydride) (SMA). RSCMs exhibited a spherical shape and were homogeneous with an average diameter of 106.1 nm and a low polydispersity of 0.087. In comparison, after crosslinking the micelles possessed better stability against dilution and stronger redox-response towards dithiothreitol (DTT). The SMA micelles displayed high drug loading capacity for hydrophobic DOX with a drug loading of approximately 14.1–19.2% (w/w) and an encapsulation efficiency of 72.1–82.7% (w/w). The in vitro release studies of shell crosslinked micelles showed that DOX release was minimal (<25%, 24 h) under physiological conditions. However, in the presence of 10 mM DTT, accelerated release of DOX was achieved (60%, 24 h). MTT assays in B16F10 cells indicated that RSCMs displayed low cytotoxicity up to a concentration of 500 μg ml−1. Moreover, the IC50 value showed that cRGD-DOX-ss-M could be more effective than other groups. In vitro, cellular uptake was further studied with confocal laser scanning microscopy and flow cytometry, both the qualitative and quantitative results demonstrated that cRGD-DOX-ss-M possessed much better specificity to cancer cells and superior stimulated release property in cytoplasm. Notably, cRGD-DOX-ss-M could more efficiently be delivered to and release into the nuclei of αvβ3 integrin over expressing tumor cell line (B16F10) than counterparts of integrin-deficient tumor cells (Hela). Thus, these cRGD-modified redox-sensitive micelles have appeared as a technology platform with great potential for targeted anticancer drug delivery and release for integrin over expressing tumor cells.
研究领域:
药剂学
·
肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）