ACS Applied Bio Materials
·
2020
·
IF 0
Shuting Lu,Xiaocheng Fan,Henan Wang,Yuliang Zhao,Wancheng Zhao,Mengzhu Li,Rongyao Lv,Ting Wang,Tiedong Sun
Betulinic acid (BA) is a natural antitumor agent and has biological activity against multiple human tumor cell lines with low cytotoxicity to normal cells, while the high hydrophobicity and the short half-life of this compound limit its clinical application. Here, gelatin-based dual-targeted nanoparticles of BA are promising to solve this problem. Hydrophobic BA is loaded in cyclodextrin to increase its solubility and prolong the circulation time in vivo. The nanoscale drug delivery systems can further enhance the bioavailability and the antitumor effect of BA and are passively targeted to the tumor tissue sites by enhanced permeability and retention effect. The RGD sequence of gelatin specifically recognizes tumor cells and brings agents into tumor cells. The nanoparticles were characterized by transmission electron microscopy, Fourier transform infrared, nuclear magnetic resonance, etc. In addition, we observed antitumor activity of the nanoparticles using both cell-based assays and mouse xenograft tumors, which proved that betulinic acid/gelatin-γ-cyclodextrin nanoparticles had a better tumor inhibition effect than betulinic acid/γ-cyclodextrin inclusion compound.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2022
·Vol. 110
·期 8
·1789-1795
·
IF 3.405
Xuan Chen,Shuting Lu,Fengrong Gong,Xiaoyu Sui,Tingting Liu,Ting Wang
Betulinic acid (BA), a natural pentacyclic lupine-type triterpene, has shown its prominent efficiency on the selective antitumor activity. However, its poor water solubility and bioavailability have limited its application. Herein, targeting nanoparticles were prepared to improve BA-based liposome (BL)'s restricted chemotherapeutic efficacy. Multi-layers membranes from the cancer cells were added as highly penetrative targeting ligands to functionalize the BA-based liposomes. In vitro experiments including the MTT assay and the fluorescence imaging of live/dead staining were adopted to prove its great inhibition in the growth of tumor cells. And it manifests that the antitumor efficacy of BL coated with cell membranes (BLCM) achieves nearly 4.3 times as that of BL under the same conditions in the MTT experiments. In addition, the fluorescence imaging stained with DAPI-FITC was applied to prove the targeting positioning effects on the BLCM. In a nutshell, the nanomedicine has good targeting antitumor efficacy and has great potential in being applied for the personalized cancer clinical treatment.
研究领域:
药理学
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 4
·948
·
IF 3.267
Yuqin Yang,Tianxin Xie,Xuehao Tian,Nana Han,Xiaojing Liu,Hongshan Chen,Jinchai Qi,Feng Gao,Wen Li,Qianwen Wu,Su Huo,Yuhao Gu,Ziqi Dai,Penglong Wang,Haimin Lei
Betulinic acid (BA) is a star member of the pentacyclic triterpenoid family, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, 21BA-nitrogen heterocyclic derivatives were synthetized, in addition to four intermediates, 23 of which were first reported. Moreover, they were screened for in-vitro cytotoxicity against four tumor cell lines (Hela, HepG-2, BGC-823 and SK-SY5Y) by a standard methylthiazol tetrazolium (MTT) assay. The majority of these derivatives showed much stronger cytotoxic activity thanBA. Remarkably, the most potent compound7e(the half maximal inhibitory concentration (IC50) of which was 2.05 ± 0.66 μM) was 12-fold more toxic in vitro thanBA-treated Hela. Furthermore, multiple fluorescent staining techniques and flow cytometry collectively revealed that compound7ecould induce the early apoptosis of Hela cells. Structure–activity relationships were also briefly discussed. The present study highlighted the importance of introducing nitrogen heterocyclic rings into betulinic acid in the discovery and development of novel antitumor agents.Keywords:betulinic acid;BA-nitrogen heterocyclic derivatives;antitumor;Hela;flow cytometry
研究领域:
药物化学
·
肿瘤学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Huafang Ding,Xiaqing Wu,Junhui Pan,Xing Hu,Deming Gong,Guowen Zhang
Betulinic acid (BA), an important pentacyclic triterpene widely distributed in many foods, possesses high antidiabetic activity. In this study, BA was found to exhibit stronger inhibition of α-glucosidase than acarbose with an IC50 value of (1.06 ± 0.02) × 10–5 mol L–1 in a mixed-type manner. BA bound with α-glucosidase to form a BA−α-glucosidase complex, resulting in a more compact structure of the enzyme. The obtained concentrations and spectra profiles of the components resolved by the multivariate-curve resolution–alternating least-squares confirmed the formation of the BA−α-glucosidase complex. Molecular docking showed that BA tightly bound to the active cavity of α-glucosidase, which might hinder the entrance of the substrate leading to a decline in enzyme activity. The chemical modification of α-glucosidase verified the results of the computer simulation that the order of importance of the four amino acid residues in the binding process was His > Tyr > Lys > Arg.
研究领域:
药理学
·
生物化学
·
计算生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）