JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Songzhi Xie,Long Zhao,Xiaojie Song,Maosheng Tang,Chuanfei Mo,Xiaohong Li
The use of bacteria as drug carriers meets several challenges, such as biocompatibility, motility deterioration after drug loading and lack of in vivo verification. Escherichia coli Nissle 1917 (EcN) is one of the best studied probiotic strains, and doxorubicin (DOX) is conjugated onto EcN in the current study via acid-labile linkers of cis -aconitic anhydride (EcN-ca-Dox), realizing the bacteria-directed accumulation and acid-responsive release of anticancer drugs in tumors. The drug conjugation has maintained the bacterial motion profiles of over 9 μm/s and cell viability of over 70%. After 3 h and 3 days of intravenous injection of EcN-ca-Dox, DOX accumulations in tumors are determined as 12.9% and 6.4% of the injected doses per gram of tissue, respectively, which are much higher than the commonly used nanocarriers . Compared with free DOX and DOX-conjugated EcN via stable linkers of succinic anhydride , the EcN-ca-Dox treatment improves the antitumor efficacy with respect to the tumor growth inhibition, prolongation of animal survivals, and apoptosis induction of tumor cells. In addition, EcN has been cleaned off from tumors and other tissues after antimicrobial treatment. Thus, the acid-labile EcN conjugates provide a safe and concise strategy to enhance the temporal and spatial controllability of anticancer drugs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2019
·Vol. 95
·期 1
·58-65
·
IF 2.256
Songtao Li,Hongling Zhao,Yanfang Fan,Guiqin Zhao,Ruxing Wang,Fuyu Wen,Jianping Wang,Xiaohui Wang,Yu Wang,Yang Gao
In this study, a peptide–drug conjugate was designed and synthesized by connecting a transferrin receptor (TfR)-targeted binding peptide analog BP9a (CAHLHNRS) with doxorubicin (DOX) through N-succinimidyl-3-maleimidopropionate (SMP) as the cross-linker. Confocal laser scanning microscopy results indicated that free DOX mainly accumulated in the nuclei of both TfR overexpressed HepG2 hepatoma cells and L-O2 normal liver cells expressing low level of TfR; most of the BP9a-DOX conjugate displayed cytoplasmic location, and its cellular uptake by HepG2 cells was obviously reduced by TfR blockage test. Nevertheless, the cellular uptake of this conjugate by L-O2 cells was much less than that of free DOX. Meanwhile, the BP9a-DOX conjugate exhibited lower in vitro antiproliferative activity against HepG2 cells than free DOX, but its cytotoxic effect on L-O2 cells was decreased compared with that of free DOX. These results suggest that BP9a could be applied as a potential TfR-targeted peptide vector for selective drug delivery.
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2021
·
IF 7.991
Chunxiao Gao,Yuanyuan Ma,Deyue Yan,Lianzhen Chen,Wei Yuan,Jie Ma
Nanodrug self-assembled by amphiphilic small molecules were proved to be important resource of medicine. In this study, a nanodrug of hydrophobic doxorubicin (DOX)linked to lactose (Lac) via pH sensitive acylhydrazide bond was used as a carrier to entrap the hydrophobic doxorubicin to form drug-loaded nanoparticles (Lac-DOX/DOX). We hope the increased drug to ligand ratio will improve the targeting efficiency of the nanodrug, which leads to better toxicity. The in vitro and in vivo experiments proved that with this nanodrug of Lac-DOX/DOX, we achieved active targeting, passive targeting and physical–chemical targeting through asialoglycoprotein receptor(ASGPR) on liver cancer cells, EPR effect of tumor tissue and acidic tumor microenvironment. This multiple combination can inhibit hepatoma cell proliferation, promote apoptosis, induce immunogenic cell death (ICD) and improve the anti-tumor effect.
✓ 已验证
DOI
高影响因子
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-17
·
IF 4.996
Zhang Ying,Li Kaiting,Han Xiaoyu,Chen Qing,Shao Lan,Bai Dingqun
In the course of chemotherapy for breast cancer, doxorubicin (DOX) is one of the most commonly prescribed agents. However, it has been recognized as clinically circumscribed on account of its poor selectivity and toxic reactions to normal tissues. Fortunately, the distinct merit of photochemical-responsive nanoparticle delivery systems to enhance cellular drugs uptake through localized concentration, adequate selective and minimizing systemic toxicity has aroused substantial interest recently. In this study, we synthesized photochemical-responsive nanoparticle by incorporating DOX, curcumin (CUR), and perfluorooctyl bromide (PFOB) into poly(lactic-co-glycolic acid) (PLGA) via double emulsification (DOX–CUR–PFOB–PLGA). The synthesized composite nanoparticles, which featured good ultrasound imaging, engendered photochemical activation for drug release when given laser irradiation. Cumulative release rates for DOX were 76.34%, and for CUR were 83.64%, respectively. Also, MCF-7 cells displayed significant intracellular DOX uptake and reactive oxygen species (ROS) levels, degraded cytoskeleton, and decreased cell growth and migration capacity. At the molecular level, cellular pAKT levels decreased, which resulted in downregulated HIF-1α and BAX/BCl-2 levels, leading to Caspase-3 activation and thus induction of apoptosis. Therefore, the photochemical-responsive nanoparticles possess the potential to elicit apoptosis in MCF-7 cells via enhanced DOX uptake.
✓ 已验证
DOI
PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
·
2025
·
IF 3.2
Sicong Xie,Cheng Chang,Rongxing Jiang,Lifeng Wang,Yunli Yang,Zongjin Li,Yang Zhang
PurposeThis study investigated the mechanism by which Rosmarinic acid (RA) may alleviate doxorubicin (DOX)- induced cardiomyocyte apoptosis.MethodsThe target genes of RA, DOX-related differentially expressed genes, and GEO database related genes were retrieved by bioinformatics analyses. The results of these analyses were further intersected to identify candidate genes. The protein-protein interaction network was constructed to develop the pharmacophore model. The molecular docking was simulated to determine the core target B-cell lymphoma 2-like 1 (BCL2L1) for subsequent molecular mechanism investigation in vitro. The effects of DOX and RA on the apoptosis of H9c2 cells were assessed using the CCK8 assay. The present study investigated the effect of RA on DOX-induced oxidative stress in cardiomyocytes. This investigation was conducted using an ELISA test and a DCFH-DA probe. The JC-1 probe was utilized to assess the effect of RA on DOX-induced cardiomyocyte mitochondrial membrane permeability. A Western blot assay was conducted to ascertain the activation of multiple signaling molecules, including those belonging to the BCL-2 and caspase-3 families, within the apoptosis pathway.ResultsA total of 17 differentially expressed genes (DEGs) were screened, and five genes were selected as hub DEGs. A subsequent KEGG enrichment analysis revealed that these DEGs were significantly enriched in various biological processes and pathways, including the MAPK signaling pathway, autophagy, apoptosis, and the TNF signaling pathway. The pharmacophore model and molecular docking of five candidate targets with RA were successfully established. It is noteworthy that DOX treatment led to a suppression of SOD and GSH levels, an exacerbation of oxidative stress, and a promotion of cardiomyocyte apoptosis. Furthermore, it has been demonstrated to suppress mitochondrial membrane permeability. Subsequent RT-qPCR analysis of the hub genes revealed that only BCL2L1 exhibited significant alterations. Treatment with DOX altered the expression levels of apoptosis-associated proteins, BCL-2 family members, and caspase-3 family members. However, the administration of RA mitigated the deleterious effects of DOX on cardiomyocytes.ConclusionsThe protective effects of RA may against myocardial cell apoptosis are likely mediated through its activation of BCL2L1 and inhibition of caspase cascade protein expression in myocardial cells.
✓ 已验证
DOI
PubMed
高影响因子
CARBON
·
2012
·
IF 5.378
Qi Zhang,Weiwei Li,Tao Kong,Ruigong Su,Ning Li,Qin Song,Mingliang Tang,Liwei Liu,Guosheng Cheng
We experimentally and theoretically investigated the influence of a model drug, doxorubicin (DOX) on GO interlayer interaction by evaluating the pyrolysis activation energy using thermogravimetric analysis and a mathematical model. It was found that the pyrolysis activation energy of DOX-loaded GO decreased from 145.8 to 119.5 kJ/mol with DOX loading content increasing from 0 to 186.6 w/w%. Theoretical simulation showed that the reduced activation energy could be ascribed to the gradually decreased interlayer interaction with DOX molecule intercalation. This involved distorted π–π stacking originating from the enlarged interlayer distance , and partially blocked interlayer hydrogen bonding . Our study suggested the possibility of tailoring the interlayer interaction and macroscopic properties of GO composites by controlling the density of molecules on the individual sheet, and offered a better understanding of inserted molecules causing interlayer interaction changes.
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Wei-liang Chen,Shu-di Yang,Fang Li,Ji-zhao Li,Zhi-qiang Yuan,Wen-jing Zhu,Yang Liu,Xiao-feng Zhou,Chun Liu,Xue-nong Zhang
Internal stimuli, such as intracellular lysosomal pH, enzyme, redox and reduction, can be applied to improve biological specificity of chemotherapeutic drugs for cancer therapy. Thus, functionalized copolymers based on their response to specific microenvironment of tumor regions have been designed as smart drug vesicles for enhanced anti-cancer efficiency and reduced side effects . Herein, we reported dually pH/reduction-responsive novel micelles based on self-assembly of carboxymethyl chitosan-cysteamine- N -acetyl histidine (CMCH-SS-NA) and doxorubicin (DOX). The tailor-made dually responsive micelles demonstrated favorable stability in normal physiological environment and triggered rapid drug release in acidic and/or reduction environment. Additionally, the nanocarriers responded to the intracellular environment in an ultra-fast manner within several minutes, which led to the pinpointed release of DOX in tumor cells effectively and ensured higher DOX concentrations within tumor areas with the aid of targeted delivery, thereby leading to enhanced tumor ablation. Thus, this approach with sharp drug release behavior represented a versatile strategy to provide a promising paradigm for cancer therapy.
✓ 已验证
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Yuling Bao,Qian Hu,Xiuping Wang,Xiaobo Feng,Yu He,Yuanyuan Guo,Dehao Fu
There are plenty of evidences to show that combining of chemotherapy and immunotherapy should be a very potent anti-cancer therapeutic method. In this research, we evaluated the anti-tumor activity of doxorubicin prodrug combined with erythrocyte membrane-enveloped polymer nano-vaccine against tumor in vitro and in vivo . We also analyzed the immune cell populations to investigate the effect in the tumor microenvironment and explored the inhibitory of lung metastasis. Our study showed that chemo-immunotherapy could inhibit the growth of melanoma tumor in mice. This combination approach promoted a stronger immune response by up-regulating the expression of dendritic cells and cytotoxic T cells in lymph nodes and increased the secretion of cytokines. It also restricted the immunosuppressive environment through inhibiting expression of regulatory T cells. It suggested that combination of prodrug and nano-vaccine achieved better anti-tumor effect than monotherapy, which should be widely valued and further studied to establish in a more economical and efficient way, expected to apply in the future clinical practice of cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Yuguang Yang,Wei Cui,Jie Zhao
Drug resistance is the main challenge in cancer treatment by chemotherapy. To overcome the problems, photodynamic therapy (PDT) can be introduced to increase the internalization of chemotherapeutics. Herein, we design and fabricate core-shell nanostructures for the increased therapy effect of drug resistant cancers. Human serum albumin (HSA) is conjugated with Rose Bengal (RB) (HSA-RB) to improve the endocytosis efficiency of the photosensitizer . Then we fabricated a core-shell nanostructure by coating with doxorubicin (DOX)-loaded CaCO 3 (CaCO 3 @DOX) with HSA-RB and dialdehyde carboxymethyl cellulose (DCMC) via a layer-by-layer technique. The formed CaCO 3 @DOX@(HSA-RB/DCMC) n nanostructures can be easily endocytosed by DOX resistant cancer cells (MCF-7/ADR) in the presence of low dose PDT, and greatly prevent the proliferation of cancer cells by the synergistic effect of PDT and chemotherapy. The nanostructures present efficient methods to solve drug resistance problems in the cure of cancers.
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Wenchuan She,Ning Li,Kui Luo,Chunhua Guo,Gang Wang,Yanyan Geng,Zhongwei Gu
Heparin drug conjugates are currently investigated as excellent candidates for drug delivery vehicles. In this study, we report the preparation and characterization of dendronized heparin–doxorubicin (heparin–DOX) conjugate as pH-sensitive drug delivery vehicle by combination of the features of dendrimer and heparin. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the dendronized heparin–DOX conjugate self–assembled into compact nanoparticles with negatively charged surface . The nanoparticles with 9.0 wt% (weight percent) of doxorubicin (DOX) showed pH-sensitive property due to the faster drug release rate at pH 5.0 and slow release rate at pH 7.4 aqueous. The nanoparticles were shown to effectively kill cancer cells in vitro . Notablely, the nanoparticles resulted in strong antitumor activity , high antiangiogenesis effects and induced apoptosis on the 4T1 breast tumor model due to the evidences from mice weight shifts, tumor weights, tumor growth curves, immunohistochemical assessment and histological analysis . It's also noteworthy that dendronized heparin and its nanoparticle with drug demonstrated no significant toxicity to healthy organs of both tumor–bearing and healthy mice, which was confirmed by histological analysis compared with free drug DOX. The dendronized heparin–DOX conjugate based nanopatilce with high antitumor activity and low side effects may be therefore a potential nanoscale drug delivery vehicle for breast cancer therapy.
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 8
·期 1
·189-200
·
IF 5.251
Jianghua Li,Yang Zhang,Chao Cai,Xiaozhi Rong,Meng Shao,Jiarui Li,Chendong Yang,Guangli Yu
Hepatocellular carcinoma (HCC) patients suffer from severe pain due to the serious systemic side effects and low efficiency of chemotherapeutic drugs, and it is important to develop novel drug delivery systems to circumvent these issues. In this study, a series of galactose-based glycopolymers, poly(N-(prop-2-enoyl)-β-D-galactopyranosylamine)-b-poly(N-isopropyl acrylamide) (pGal(OH)-b-pNIPAA), were prepared through a sequential reversible addition-fragmentation chain transfer (RAFT) polymerization and tetrabutylammonium hydroxide (TBAOH)-mediated removal of acetyl groups. Hydrophilic doxorubicin hydrochloride was introduced to undergo collaborative assembly with poly(N-(prop-2-enoyl)-β-D-peracetylated galactosamine)-b-poly(N-isopropyl acrylamide) (pGal(Ac)-b-pNIPAA) via TBAOH treatment. pGal-b-pNIPAA/doxorubicin (DOX) delivery nanoparticles (GND NPs) formed by collaborative assembly were fully characterized by NMR, TEM and FT-IR, indicating the well-controlled formation of particles with uniform size and high efficiency in terms of drug loading and encapsulation compared with conventional adsorption methods. Meanwhile, the GND NPs were observed to be rapidly disintegrated under acidic conditions and resulted in an increased release of DOX. Cellular experiments showed that pGal-b-pNIPAA/DOX is apparently an asialoglycoprotein receptor (ASGPR)-mediated target of HCC, resulting in enhanced cellular uptake to HepG2 cells and anti-tumor efficacy in vitro. Furthermore, GND NPs III exerted more sustainable and effective anti-tumor effects compared to free DOX on a transgenic zebrafish TO(KrasG12V) model in vivo. These results indicated that the biocompatible nanomaterials developed by collaborative assembly with galactosyl diblock glycopolymers and DOX may serve as a promising candidates for targeting therapy of HCC.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2017
·
IF 2.31
Mazhar Ali Raja,Muhammad Arif,Chao Feng,Shah Zeenat,Chen-Guang Liu
A novel pH-responsive polymer based on amphiphilic N-acetyl histidine and arginine-grafted chitosan was synthesized using N-acetyl histidine as hydrophobic segment and arginine as hydrophilic segment by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-mediated coupling reactions as anticancer drug delivery system for doxorubicin. The structure of the synthesized polymer was confirmed by Fourier transform infrared and 1H nuclear magnetic resonance analysis. Due to self-association behavior, N-acetyl histidine and arginine-grafted chitosan structured nanoparticles with in size range of 204 nm. N-acetyl histidine and arginine-grafted chitosan with different substitution degree of N-acetyl histidine were initially prepared and characterized. The critical micelle concentration decreased with increasing substitution degree of N-acetyl histidine. Furthermore, N-acetyl histidine and arginine-grafted chitosan nanoparticles exhibited an acidic pH-triggered aggregation and disassembling nature. The doxorubicin-encapsulated nanoparticles based on synthesized conjugate (N-acetyl histidine and arginine-grafted chitosan/doxorubicin nanoparticles) showed a sustained drug release pattern, which could be hastened under acidic pH conditions but delayed with increasing substitution degree of N-acetyl histidine. Anticancer effects demonstrated that N-acetyl histidine and arginine-grafted chitosan/doxorubicin nanoparticles could suppress both sensitive and resistant human breast tumor cell line (MCF-7) efficiently in a dose- and time-dependent pattern. Confocal microscopy results evidenced increased cellular uptake and enhanced retention of the synthesized nanoparticles in drug-resistant cells demonstrating better efficacy of nanoparticles over native doxorubicin. These results suggest that N-acetyl histidine and arginine-grafted chitosan/doxorubicin nanoparticles might be promising carriers for delivery of hydrophobic drug doxorubicin against drug-resistant tumors.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）