BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Wei Fu,Zhiming Hong,Xujun You,Jing Din,Baishu Chen,Beibei Zhao,Gengyan Yuan,Qixin Li
Docetaxel (Doc) is the gold standard of care for castration-resistant prostate cancer (CRPC) patients, although the therapeutic effects are modest. Fuzheng Yiliu decoction (FZYL) comprises multiple herbs, and has been used for >10 years to treat various cancers, including hepatocellular tumors, malignant gastrointestinal tumors, and prostate cancer. In the study reported, we evaluated the anticancer effects of FZYL and of a combination of Doc and FZYL in CRPC tumor-bearing mice, and explored the underlying mechanisms. PC-3 tumor-bearing mice were treated with FZYL, Doc, Doc + FZYL or vehicle solution. Tumor volume was monitored, and tumor weight, proliferation and apoptosis of tumor tissues were measured. Deep sequencing was used to profile the miRNA expression patterns in tumor tissues. Our results suggested that FZYL alone could depress tumor growth, and the combination of Doc and FZYL treatment exhibited enhanced anticancer effects. Doc + FZYL regulated the expression of 10 miRNAs: miR-34b-5p, miR-674-3p, miR-140-3p, miR-342-3p, miR-214-3p, miR-149-5p, miR-378c, miR-29b-3p, miR-218-5p, and miR-378a-3p, involving in the PI3K-Akt pathway in the treatment of CRPC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Jing Li,Jun Zhang,Yiyue Wang,Xiao Liang,Zaitongguli Wusiman,Yunzhi Yin,Qi Shen
Metastasis impedes the successful chemotherapy for breast cancer. In this study, an Akt inhibitor (quercetin, Qu) was co-delivered with a chemotherapeutic agent (docetaxel, DTX) by using hyaluronic acid (HA)-modified nanoparticles (NPs) as vectors to block metastasis. Dual DTX/Qu-loaded HA/polylactic-co-glycolic acid–polyethyleneimine NPs (PP-HA/NPs) were prepared through a modified emulsion solvent evaporation technique. The particle size of PP-HA/NPs with narrow polydispersity was 209.8 ± 10.8 nm. Wound healing assay revealed that Qu co-delivery and HA modification elicited synergistic inhibitory effects on cell motility. The downregulation of p-Akt and matrix metalloproteinase-9 (MMP-9) expression contributed to the significant inhibition of cell migration and invasion with inhibition rates of 95.6% and 99.3%, respectively. Further studies indicated that PP-HA/NPs could be efficiently uptaken by 4T1 breast cancer cells and could further induce cytotoxicity, decrease colony formation and promote cell apoptosis. Biodistribution assay demonstrated PP-HA/NPs also enhanced drug accumulation in the tumor and lungs and predicted that PP-HA/NPs could be employed as an effective therapy for primary tumor and pulmonary metastasis . Therefore, PP-HA/NPs could be a promising delivery system to treat metastatic breast cancer effectively.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
细胞生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 5
·964
·
IF 6.525
Yingying Zhang,Hongxia Duan,Heming Zhao,Lingling Qi,Yanhong Liu,Zheao Zhang,Chao Liu,Liqing Chen,Mingji Jin,Youyan Guan,Zhonggao Gao,Wei Huang
Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways.Keywords:prostate cancer;androgen receptor;siRNA delivery;docetaxel;PSMA targeting
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Qingfa Guo,Fanyuan Kong,Xiaoru Pan,Shuhua Cao
Recent findings revealed that low-concentration paclitaxel(DTX) could enhance cytotoxicity by upregulating p53 expression in lung cancer cell lines. So, co-delivery of DTX and RFP-p53 gene with PEA nanoparticles (NPs) was studied. The prepared DTX loaded PEA NPs (PEA/DTX) were characterized by particle size distribution, morphology, zeta potential, and crystallography and cytotoxicity. Results showed that the PEA/DTX NPs had a mall particle size (≤100 nm), moderate zeta potential (≥40 mV) and drug loading of 9.0%, DTX was released from PEA/DTX NPs in an extended period in vitro. More important, agarose gel electrophoresis showed that PEA/DTX cationic NPs were able to completely bind RFP-p53 gene with mean particles size and zeta potential. Studies on cellular uptake of (PEA/DTX)/RFP-p53 NPs demonstrated that both drug and gene were effectively taken up by A549 tumor cells. It was found that intravenous injection of (PEA/DTX)/RFP-p53 NPs efficiently inhibited growth of subcutaneous A549 carcinoma in vivo (p < 0.05) and was significantly less side effect than that of mice treated with the other groups. Therefore, the (PEA/DTX)/RFP-p53 NPs might be a promising candidate for A549 cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2015
·Vol. 17
·期 5
·1-14
·
IF 2.184
Zhao Qian,Li Nannan,Shu Chang,Li Ruixin,Ma Xiaona,Li Xuequan,Wang Ran,Zhong Wenying
Abstract A novel antitumor drug delivery system, docetaxel (DTX)-loaded oxidized single-wall carbon nanohorns (oxSWNHs) with anti-VEGF monoclonal antibody (mAb) as a target agent was constructed. DTX was absorbed onto the oxSWNHs via the physical adsorption or π–π interaction. DSPE–PEG–COOH was non-covalently wrapped to the hydrophobic surface of oxSWNHs to improve its water solubility and biocompatibility. The mAb was bonded to the PEG through amide bond. The DTX@oxSWNHs-PEG-mAb (DDS) exhibited suitable particle size (191.2 ± 2.1 nm), good particle size distribution (PDI: 0.196), and negative zeta potential (−24.3 ± 0.85 mV). These features enhanced permeability and retention (EPR) effect and reduced the drug molecule uptake by the reticuloendothelial system. The in vitro drug release followed non-Fickian diffusion ( n = 0.6857, R = 0.9924) with the cumulative release of DTX 59 ± 1.35 % at 72 h. Compared with free DTX, the DDS enhanced the cytotoxicity in MCF-7 cell lines in vitro efficiently (IC 50 : 2.96 ± 0.6 μg/ml), and provided higher antitumor efficacy (TGI: 69.88 %) in vivo. The histological analysis indicated that the DDS had no significant side effect. Therefore, the new DDS is promising to attain higher pharmaceutical efficacy and lower side effects than free DTX for cancer therapy. The research demonstrated that DTX@oxSWNHs-PEG-mAb might have promising biomedical applications for future cancer therapy. Graphical Abstract
研究领域:
纳米医学
·
肿瘤学
·
药剂学
✓ 已验证
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2021
·
IF 6.598
Lingxiao Li,Shiyi Zuo,Fudan Dong,Tian Liu,Yanlin Gao,Yinxian Yang,Xin Wang,Jin Sun,Bingjun Sun,Zhonggui He
Homodimeric prodrug-based self-assembled nanoparticles, with carrier-free structure and ultrahigh drug loading, is drawing more and more attentions. Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage. The influence of the linkages on the self-assembly, in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research. Herein, three docetaxel (DTX) homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages. Interestingly, compared with the other two linkages, the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs, thus improving the stability, circulation time and tumor targeting of prodrug nanoassemblies. Besides, the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells. Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells, their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells, which finally “turned the table”. Our study illustrates the crucial role of linkages in homodimeric prodrugs, and gives valuable proposal for the development of advanced nano-DDS for cancer treatment.
研究领域:
药学
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2018
·
IF 2.297
Yunzhi Yin,Yiyue Wang,Jun Zhang,Jing Li,Jingjing Chen,Qi Shen
Docetaxel (DTX) is one kind of well-known anticancer drugs against tumors. GDC0941 was used to inhibit PI3K/Akt signal pathway and improve anti-tumor activity. PLGA-PEG-R7 (poly lactic-co-glycolic acid polyethylene glycol bending with cell penetrating peptide R7)/poly sulfadimethoxine-Folate nanoparticles (R7/PSD-Fol NPs) were made to load DTX and GDC0941 simultaneously. In vitro, the release capacity of DTX and GDC0941 inside nanoparticles was determined and both drugs could release from nanoparticles to 70% within 48h. The result of flow cytometry showed that GDC0941 had no interference on cell uptake and R7/PSD-Fol NPs could enhance MCF-7 cells uptake the most significantly. In cell colony study, GDC0941 could further improve the anti-tumor effect of DTX and inhibit the formation of cell clones on the basis of enhancing the uptake of R7/PSD-Fol NPs. The capability of cell colony formation was as follows: DTX > DTX + GDC0941 > R7 NPs > R7/PSD-Fol NPs. The expression of cell apoptosis proteins treated with R7/PSD-Fol NPs was the lowest. The addition of GDC0941 could decrease the full-length content of apoptotic proteins caspase-3 and caspase-9. In vivo, pharmacokinetic parameters results showed us that GDC0941 had no interference on pharmacokinetic study. Main pharmacokinetic parameters of DTX suspension and R7/PSD-Folate NPs suspension showed significant differences.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2014
·
IF 0.872
Ruiduan Li,Jianjun Zhang,Jianfeng Chen,Wei Teng,Jiexin Wang,Caixia Li
Hybrid nanoparticles based on lactide and poly(ethylene glycol) were composed of a copolymer , poly(2-amino,1,3-propanediol carbonic ester-co-lactide) [P(LA-co-CA)], and a graft copolymer , poly(2-amino,1,3-propanediol carbonic ester-co- l -lactide)-g-methoxy-poly(ethylene glycol) [P(LA-co-CA)-mPEG]. The hybrid nanoparticles were prepared using emulsion solvent diffusion method. The copolymer of poly(2-benzyloxy amide,1,3-propanediol carbonic ester-co-lactide) was prepared using ring-opening polymerization with diethylzinc (ZnEt 2 ) as a catalyst, and then took off benzyl oxygen group to obtain P(LA-co-CA). P(LA-co-CA)-mPEG by grafting methoxy-PEG-propionaldehyde (mPEG-ALD) on P(LA-co-CA). With docetaxel as a model drug, the morphology of nanoparticles was characterized by scanning electron microscopy (SEM) and the size and size distribution were determined by dynamic light scattering (DLS). The size of DTX-loaded particle was approximately 110 nm. The size scale prevents them from uptake by the reticulo-endothelial system and accumulation at the target site through the enhanced permeability and retention effect. In MTT assay, the results showed that the polymers are non-cytotoxic. The study points to the potential application of the composite nanoparticles in biomedical applications, including tissue engineering and controlled drug delivery.
研究领域:
生物材料学
·
药剂学
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2018
·
IF 4.56
Shu Han,Ruiyang Sun,Hong Su,Jing Lv,Huan Xu,Di Zhang,Yuanshan Fu
This study aimed to investigate the ability of the novel materials D -α-tocopheryl poly(2-ethyl-2-oxazoline) succinate (TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and 1 H-NMR. The buffering capacity of polyethylene glycol- distearoyl phosphatidylethanolamine (PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel (DOC) liposomes (TPOS-DOC-L) had a slower drug-release rate at pH 7.4 similar to PEGylated-DOC liposomes (PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes (TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4 ( P < 0.01). Conversely, for PEGylated C6 liposomes (PEG-C6-L) and conventional C6 liposomes (C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes (DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-L significantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.
研究领域:
药剂学
·
药物递送系统
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 28
·18004-18011
·
IF 4.036
Lingling Xu,Chuan Zhou,Fan Wang,Huiqin Liu,Guangyuan Dong,Siyi Zhang,Tao Liu
In this study, a drug delivery system was prepared by grafting the targeting molecule arginine-glycine-aspartic acid (RGD) onto hyperbranched polyglycerol (HPG)-modified β-cyclodextrin (β-CD-HPG) for the targeted inhibition of nasopharyngeal carcinoma (NPC) cells. The obtained β-CD-HPG-RGD with a relatively small size and low surface charge delivered docetaxel (Doc) effectively and displayed a targeting effect to human NPC HNE-1 cells, as confirmed by confocal laser scanning microscopy and flow cytometry. The in vitro drug release analysis exhibited the controlled drug release kinetics of the β-CD-HPG-RGD/Doc nanomedicine. β-CD-HPG-RGD/Doc effectively inhibited the proliferation of HNE-1 cells and promoted apoptosis. Moreover, its biocompatibility in vitro and in vivo was assessed. The results indicate that the β-CD-HPG-RGD/Doc nanomedicine has potential application in NPC targeting therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Bingjun Sun,Cong Luo,Lin Li,Menglin Wang,Yuqian Du,Donghua Di,Dong Zhang,Guolian Ren,Xiaolei Pan,Qiang Fu,Jin Sun,Zhonggui He
Nanostructured lipid carriers (NLC) have been considered as promising vehicles for oral delivery of taxanes, such as docetaxel (DTX). However, the low drug loading capability (∼5%, w/w) has greatly limited their clinical application. In response to this challenge, a novel lipophilic oleate prodrug of DTX (DTX-OA) was synthesized and efficiently encapsulated in NLC using core-match technology, in which liquid lipid (OA) was used as core matrix to enhance compatibility with DTX-OA. DTX-OA-NLC showed uniform particle size of about 100 nm with markedly high drug loading capability (∼23% of DTX, w/w) compared with DTX-NLC (∼5%, w/w). Besides, DTX-OA-NLC showed better colloidal stability and slower drug release property compared with DTX-NLC. The prepared NLC could be accumulated more easily in MDCK cells than drug solution, and clathrin-mediated endocytosis was the main endocytosis pathway. In situ single-pass intestinal perfusion (SPIP) and intestinal biodistribution studies demonstrated the improved membrane permeability and intestinal wall bioadhesion of NLCs. The bioavailability of DTX-OA-NLC showed 4.04-fold and 2.06-fold higher than DTX solution and DTX-NLC, respectively. These results suggest that the core-matched prodrug-NLC is a promising platform to facilitate the oral delivery of DTX.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Jingbin Huang,He Zhang,Yuan Yu,Yan Chen,Dong Wang,Guoqing Zhang,Guichen Zhou,Junjie Liu,Zhiguo Sun,Duxin Sun,Ying Lu,Yanqiang Zhong
To develop biodegradable docetaxel-loaded self-assembled nanoparticles of poly ( d , l -lactide-co-glycolide)/hyaluronic acid block copolymers were successfully synthesized. These copolymers could form nanoparticles with small size (<200 nm), an acceptable CMC (∼7.9 mg/L), typical core/shell structure and superior stability in one week. DTX-loaded PLGA 502H -b-HA 5.6k nanoparticles (DTX/SANPs) showed a biphasic release pattern within 120 h, and exhibited enhanced cytotoxicity toward CD44-overexpressing MDA-MB-231 cells. Cellular uptake study indicated that PLGA 502H -b-HA 5.6k nanoparticles (SANPs) were taken up in MDA-MB-231 cells by CD44-mediated endocytosis . Pharmacokinetics study revealed DTX/SANPs could prolong the circulation of DTX in the blood. In vivo studies demonstrated that SANPs exhibited enhanced tumor targeting and antitumor activity with lower systemic toxicity. In conclusion, DTX/SANPs have great potential for targeted chemotherapy for CD44-overexpressing breast cancer.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）