JOURNAL OF MICROENCAPSULATION
·
2019
·
IF 2.04
Yingting Wang,Along Zuo,Xiaoyan Huang,Ying Ying,Xinsheng Shu,Xianxiong Chen,Yatao Yang,Junxian Ma,Guimiao Lin,Xiaomei Wang,Lin Mei,Gan Liu,Yingying Zhao
Taxane-based chemotherapy-loaded drug delivery systems have great potential for cancer treatment. The docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS) nanoparticles and the docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate) (PAM-PBLG) nanoparticles were designed using a modified nanoprecipitation method. The particle size, encapsulation efficiency (EE), and in vitro release characteristics of the nanoparticles were tested. The effects of the two nanoparticles on the cellular uptake and cell viability on human cervical cancer cell line Hela and the human breast cancer cell line MCF-7 were compared. Furthermore, their antitumor efficiency was evaluated through in vivo tumour growth experiment in comparison with free DTX. PAM-PBLG-b-TPGS nanoparticles displayed high EE, smaller diameter, and a nice releasing profile. Besides, based on the high EE and ‘self-controlled’ drug release of the DTX-loaded PAM-PBLG-b-TPGS nanoparticles, they exhibited stronger cytotoxicity (lower survival rate) and higher uptake rate than DTX-loaded PAM-PBLG nanoparticles in Hela cells and MCF-7 cells. Furthermore, compared with DTX-loaded PAM-PBLG nanoparticles and free DTX, DTX-loaded PAM-PBLG-b-TPGS nanoparticles produced a potent anti-tumour effect. Thus, the DTX-loaded PAM-PBLG-b-TPGS nanoparticles provide a novel attractive nanocarrier for the DTX delivery of chemotherapy to human breast cancer cells and human cervical cancer cells.
研究领域:
药剂学
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肿瘤学
·
纳米技术
·
药物递送系统
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yang Fan,Qingjie Wang,Guimei Lin,Yanbin Shi,Zili Gu,Tingting Ding
In this study, novel prodrug-modified cationic liposome nanocomplexes (Combo NCs) were reported for gemcitabine (GEM) and docetaxel (DTX) co-delivery. This nanoplatform exhibited multiple favorable characteristics, such as a ‘green’ fabrication with a one-step chemical reaction, appropriate size (∼200 nm) and distribution (PDI < 0.2), low zeta potential (−31.1 mv), high drug-loading efficiency (9.3% GEM plus 3.1% DTX, wt%) and pH and enzymatic dual-stimulus-responsive release properties. Immunofluorescence and cellular uptake studies showed that Combo NCs efficiently targeted overexpressed CD44 in MDA-MB-231 carcinoma. In vitro studies revealed that Combo NCs played a critical role in the synergistic induction of cytotoxicity, apoptosis and inhibition of wound healing. Combo NCs were confirmed to exhibit great potency for increasing S phase arrest and remodeling the CDA and dCK balance by decreasing the mRNA expression of CDA down to 0.09-fold and increasing the mRNA expression of dCK by 1.36-fold, remarkably increasing the dCK/CDA ratio to 15.3-fold compared with the blank control. The biodistribution results obtained in vivo revealed an effective accumulation in tumor foci. All of these advantages of Combo NCs contributed to their remarkable anti-tumor efficacy without systemic toxicity as well as their apoptosis-enhancing and anti-proliferative capacities, as determined by TUNEL and Ki67 immunohistochemistry in vivo . Consequently, such a rationally contemplated co-delivery system demonstrated the promising potential of clinical applications for triple-negative breast cancer therapy. State of Significance The Combo NCs were innovatively applied for co-delivery of hydrophilic GEM and hydrophobic DTX. The ester bond linking and shielding effect of HA-GEM made the carriers achieve synchronous release properties, which was determined in in vitro release study. Due to the HA modification, the vectors own great potency for positive targeting to CD44 overexpressed triple-negative breast cancer cells MDA-MB-231. Cytotoxicity and apoptosis studies confirmed the targeting effect and synergism between two drugs. Interestingly, we found in cell cycle study, drug combinations (free combination or Combo NCs) didn’t show a rise in G2M phase, which was significantly higher when treated DTX alone. We further discovered the role of DTX in combinations may involve in modulating GEM associated enzymes thus enhancing the efficacy of GEM. Consequently, this nanoplatform provided a novel solution for achieving targeted co-delivery and potentiating effect in cancer therapy.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2016
·Vol. 12
·期 7
·1463-1477
·
IF 3.929
Huang Jingbin,Tao Chun,Yu Yuan,Yu Feifei,Zhang He,Gao Jie,Wang Dong,Chen Yan,Gao Jing,Zhang Guoqing,Zhou Guichen,Liu Junjie,Sun Zhiguo,Sun Duxin,Zou Hao,Xu Hao,Lu Ying,Zhong Yanqiang
Breast cancer stem cells (BCSCs) are implicated in the initiation and progression of breast cancer and are responsible for metastasis and recurrence. In this study, we attempted to simultaneously target differentiated breast cancer cells (DBCCs) and BCSCs by using a combination of docetaxel
(DTX)- and sulforaphane (SFN)-loaded poly(D, L-lactide-coglycolide)/hyaluronic acid (PLGA-b-HA)-based nanoparticles. BCSCs were identified as having an ESA+CD44+CD24– phenotype, which exhibited docetaxel resistance. Drug-loaded nanoparticles exhibited
enhanced cytotoxicity towards both DBCCs and BCSCs compared with free drugs. SFN-loaded nanoparticles were more effective in inhibiting BCSCs than free SFN in vitro by down-regulating β-catenin expression. In vivo analysis of anti-tumor activity showed that the combination
therapy with DTX- and SFN-loaded nanoparticles had the strongest antitumor efficacy. In vivo analysis of anti-BCSCs activity showed that the self-renewal ability of BCSCs was strongly inhibited in DTX- and SFN-loaded nanoparticle-treated groups. In conclusion, the combination of SFN-
and DTX-loaded PLGA-b-HA nanoparticles shows therapeutic potential in the treatment of breast cancer by simultaneously targeting DBCCs and BCSCs.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）