ADVANCED FUNCTIONAL MATERIALS
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2015
·Vol. 25
·期 47
·7317-7326
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IF 11.805
Shi-Ying Li,Li-Han Liu,Lei Rong,Wen-Xiu Qiu,Hui-Zhen Jia,Bin Li,Fei Li,Xian-Zheng Zhang
A dual-Förster resonance energy transfer (FRET)-based versatile prodrug (V-prodrug), in which the fluorescence of both 5(6)-carboxylfluorescein (FAM) and doxorubicin (DOX) can be quenched by 4-(dimethylaminoazo)benzene-4-carboxylic acid (Dabcyl) with high quenching efficiency, is developed in this paper. The V-prodrug can selectively bind to the α v β 3 integrin overexpressed cancer cells through the Arg-Gly-Asp (RGD) targeting moiety. After that, the acid-mediated DOX release of the V-prodrug can be real-time monitored by the increase of the red fluorescence from DOX. Thereafter, DOX-induced cell apoptosis can also be in situ assessed by the fluorescence recovery of the FAM, due to the caspase-3-mediated Asp-Glu-Val-Asp (DEVD) peptide sequence cleavage. This novel prodrug provides a cascaded imaging of real-time drug release and subsequent cell apoptosis, which enables the in situ detection of the cancer response and the therapeutic efficacy evaluation of the prodrug.
研究领域:
药理学
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生物医学工程
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分子生物学
·
癌症研究
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DOI
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 60
·36862-36872
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IF 3.119
Mengru Cai,Liuying Qin,Longtai You,Yu Yao,Huimin Wu,Zhiqin Zhang,Lu Zhang,Xingbin Yin,Jian Ni
Metal organic frameworks (MOFs) are widely used in drug carrier research due to their tunability. The properties of MOFs can be adjusted through incorporation of mono-substituents to obtain pharmaceutical carriers with excellent properties. In this study, different functional groups of –NH2, –CH3, –Br, –OH and –CH2CH are connected to MOF-5 to analyse the effect of mono-substituent incorporation on drug delivery properties. The resulting MOFs have similar structures, except for Br–MOF. The pore size of this series of MOFs ranges from 1.04 nm to 1.10 nm. Using oridonin (ORI) as a model drug, introduction of the functional groups appears to have a significant effect on the drug delivery performance of the MOFs. The IRMOFs can be ranked according to drug-loading capacity: MOF-5 > HO–MOF-5 > H3C–MOF-5 = Br–MOF-5 > H2N–MOF-5 > CH2CH–MOF-5. The ORI release from ORI @IRMOFs is explored at two different pH values: 7.4 and 5.5, and the ORI@IRMOFs are ranked according to the cumulative release percentage of ORI: ORI@MOF-5 > ORI@Br–MOF-5 > ORI@H3C–MOF-5 > ORI@H2N–MOF-5 > CH2CH–MOF-5 > ORI@ HO–MOF-5. In particular, the release behaviour of ORI@MOFs is described through a new model. The different drug delivery performance of MOFs may be due to the complex interactions between MOFs and ORI. In addition, the introduction of single substituents does not change the biocompatibility of MOFs. MTT in vitro experiments prove that this series of MOFs has low cytotoxicity. This study shows that the incorporation of single substituents can effectively adjust the drug delivery behaviour of MOFs, which is conducive to realization of personalized drug delivery modes. The introduction of active groups can also facilitate post-synthesis modification to achieve coupling of targeting groups. MOFs incorporated with single substituents perform favorably in terms of use as biomedical drug delivery alternative carriers in effective drug payload and flexible drug release.
研究领域:
材料科学
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药学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Hao Chen,Dong Ye,Yuan Huang,Xinxin Luo,Xiaoyuan Wu,Jinzhi Zhang,Qichao Zou,Hangxing Wang,Suxiao Wang
Protein corona formation can lead to obstructive screening of targeting groups of nanoparticles (NPs). Also, the targeting groups are subjected to physiochemical interactions when exposed to solvents. Here, these two factors can influence NP targeting efficiency. Therefore, it is necessary to prepare a general method of preparing an anti-fouling NPs with protected targeting groups. Here, we designed α-amylase-starch double-layer coated poly (methyl methacrylate- co -acrylic acid) NPs (α-ams-SCMMA NPs), functionalized with aptamer targeting groups and doped with Tetrakis(para-hydraoxylphenyl) porphyrin (TPPOH) as a payload drug. Natural polysaccharide starch and enzyme α-amylase were applied here for thermo-sensitive activation of starch hydrolyzation in order to render the NPs' self-polishing from protein corona effects. During incubation with serum media, the protein corona was formed at the exterior shell of NPs, while the self-polishing process was activated to remove the “protein fouling” when the incubation temperature increased to 37 °C (body temperature). Mechanistically, the starch layer of α-ams-SCMMA NPs was readily hydrolysed by α-amylase, whereby the adsorbed protein corona could be efficiently eliminated and the targeting groups were then presented. With this unique self-polishing NP design, we believe our method can be applied for potential NP applications in cancer therepy due to excellent antifouling property and protected targeting groups.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
材料科学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Yunjian Yu,Jie Li,Yufei Zhang,Zhuang Ma,Haonan Sun,Xiaosong Wei,Yayun Bai,Zhongming Wu,Xinge Zhang
Intracellular bacteria-mediated antibiotic tolerance, which acts as a “Trojan horse,” plays a critical and underappreciated role in chronic and recurrent infections. Failure of conventional antibiotic therapy is often encountered because infected cells prevent drug permeation or the drug concentration is too low at the site of resident bacteria. New paradigms are therefore urgently needed for intracellular anti-infective therapy. Here, a novel therapeutic was developed for targeted delivery of antibiotics into bacteria-infected macrophages to improve drug accumulation in intracellular niches and bactericidal activity of antibiotics against intracellular pathogens. This hierarchical nanoplatform includes a glycocalyx-mimicking shell that enables rapid uptake by macrophages. Subsequently, the targeting moieties are activated in response to the bacteria, and the release of entrapped antibiotics is triggered by bacteria and bacteria-secreted enzymes . The self-immolative drug delivery nanoplatform eliminates intracellular pathogenic bacteria residing in macrophages more efficiently compared to drugs alone. The in vivo dynamically monitored nanosystem also efficiently inhibited the growth of intracellular Staphylococcus aureus in infected muscles of mice with negligible systemic toxicity. The novel dual-targeting design of an all-in-one therapeutic platform can be used as an alternative strategy to reanimate antibiotic therapy against multifarious intracellular bacterial infections.
研究领域:
纳米技术
·
药学
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传染病学
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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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Juang Wang,Zilong Zhou,Fang Zhang,Hui Xu,Wenli Chen,Tingting Jiang
We demonstrated a novel nanocomposite based on fluorescent turn-on gold nanostars for simultaneous tumor targeting photothermal therapy (PTT) and feedback apoptosis imaging of the self-therapeutic effect. In this theranostic agent ( [email protected] ), gold nanostars (AuNSs) and fluorescent dye Atto 655, as a fluorophore/quencher pair, were conjugated to form intermolecular fluorescence quenching in virtue of the linkage of a caspase-3 responsive peptide. Folic acid targeting moiety facilitated the selective accumulation in cancer cells via receptor-mediated endocytosis. Upon photo irradiation, [email protected] demonstrated excellent photothermal effect and induced cell death with apoptosis related mechanism. The typical apoptosis-effector proteases, caspase-3, was subsequently activated and terminated intramolecular fluorescent quenching process. Obvious fluorescence recovery could be applied to precisely assess the activated caspase-3 expression and the real time therapeutic efficacy. This novel versatile nanocomposite could serve as a theranostic agent for tumor targeting PTT and also provide self-therapeutic monitoring for precise cancer therapeutic applications.
研究领域:
纳米技术
·
癌症治疗
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生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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