SEPARATION AND PURIFICATION TECHNOLOGY
·
2018
·
IF 3.927
Guoqiang Cui,Xuebing Yang,Tingting Liu,Zaizhi Liu,Lei Yang
An efficient approach for enzyme-enhanced extraction using an ionic liquid solution (ILEEE) of the major alkaloidal components camptothecin (CPT) and 10-hydroxycamptothecin (HCPT) from the samara of Camptotheca acuminata is presented. The enzyme pretreatment in an aqueous ionic liquid (IL) media was used for the enhancement of extraction yield. The activity of hemicellulase was investigated in various ILs with imidazolium-based cations ([C 2 MIM] + , [C 4 MIM] + , [C 6 MIM] + , [C 8 MIM] + , [C 10 MIM] + ) and anions (Br − , Cl − , Ac − , HSO 4 − , NO 3 − ). The optimal ionic liquid for the hemicellulase extraction process was found to be a 0.75 M [C 8 MIM]Br aqueous solution. Single factor experiments and Box–Behnken design found the optimal operational parameters for ILEEE to be an incubation temperature of 40 °C, incubation time of 12 h, extraction phase of pH 4, liquid-solid ratio of 30 mL/g, 0.75 M [C 8 MIM]Br and a hemicellulase concentration of 0.441 mg/mL. Under these optimized extraction conditions, the total yield of CPT and HCPT was 1043 ± 51.2 μg/g. SEM images of the samples revealed that hemicellulases hydrolyze the cell wall, leading to structure breakdown, which enabled [C 8 MIM]Br to have a high dissolving power for the targeted components. These factors are the main causes for the increasing in the total yield of the CPT and HCPT when using the ILEEE extraction method.
研究领域:
药学
·
化学工程
·
生物技术
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DOI
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2013
·Vol. 299
·期 3
·1509-1515
·
IF 1.467
Liu Zhen-feng,Wang Guo-lin,Dong Meng-jie,Jin Jian-wen,Li Jia-jun,Zhang Qian,Zhao Kui,Yang Shu-ye,Lin Xiang-tong
The preparation of 10-(2-[ 18 F]fluoroethoxy)-20( S )-camptothecin, a potential positron emission tomography tracer for the imaging of topoisomerase I in cancers, is described. 10-(2-[ 18 F]Fluoroethoxy)-20( S )-camptothecin was synthesized by the [ 18 F]fluoroalkylation of the corresponding hydroxy precursor molecule with 2-[ 18 F]fluoroethyl bromide ([ 18 F]FEtBr) in dimethylsulfoxide (DMSO) at 55 °C for 20 min; this was followed by purification using high performance liquid chromatography (HPLC) with a total preparation time of 60 min. The overall radiochemical yield was approximately 5.4–12 % (uncorrected), and the radiochemical purity was above 96 %.
研究领域:
药理学
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核医学
·
肿瘤学
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产品关联
DOI
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 9
·5380-5396
·
IF 6.895
Yalin Sun,Yan Liang,Na Hao,Xiaoheng Fu,Bin He,Shangcong Han,Jie Cao,Qingming Ma,Wen Xu,Yong Sun
9-Nitro-20(S)-camptothecin (9-NC) is a broad-spectrum antitumor drug used in tumor treatments, but its clinical applications and antitumor efficacy are limited by its structural instability, poor solubility, and extremely low drug utilization in tumor tissues. In this study, enzyme-sensitive nuclear-targeted dual-functional polymeric micelles were developed for 9-NC delivery with a high drug loading content (12.93 ± 0.88%), steady-state circulation, and a rapid attack at the “heart” of tumor cells. Briefly, chrysin (CHR) as a π-conjugated moiety was immobilized on the PCL terminal in the TAT–PCL amphiphiles and combined with the ALAL peptide as a linker on HA chains to yield the ultimate CHR–PCL–TAT–ALAL–HA (HATPC) amphiphiles. Spherical 9-NC-loaded micelles were obtained from the self-assembly of the dual-functional amphiphiles comprising HATPC and 9-NC with uniform nanosize (121.6 ± 5.79 nm), well-distributed morphology (PDI: 0.256), and negative surface charge (−23.2 ± 0.5 mV), yielding high stability during blood circulation. In this drug delivery system, HA acts as an active tumor-targeting instrument via CD44-receptor-mediated endocytosis; further, the ALAL peptide could be cutoff in the lysosomes of the tumor cells due to the high expression of cathepsin B, leading to lysosomal escape, while the secondary polymeric micelles targeted the tumor cell nucleus via the exposed TAT peptide. The enzyme sensitivity and nuclei targetability of the 9-NC/HATPC micelles were confirmed by dynamic light scattering and confocal laser scanning microscopy analyses. As compared to free 9-NC and traditional mPEG2k–PCL2k polymeric micelles, 9-NC/HATPC micelles were the most concentrated in the tumor cell nucleus; therefore, they exhibited the highest cytotoxicity against SKOV3 tumor cells both in vitro (IC50 = 0.03 μg mL−1) and in vivo. This enzyme-sensitive nuclear-targeted dual-functional drug delivery system involving HATPC provided a new and promising strategy for enhanced 9-NC delivery and antitumor efficacy.
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Wenxiu He,Yue Jiang,Qian Li,Di Zhang,Zhonghao Li,Yuxia Luan
Self-assembled nanovehicles of chemotherapy drug with photothermal agent are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most of the drugs and photothermal agents have poor water solubility and poor interactions to drive the formation of self-assembled nanovehicles, which is a bottleneck of co-assembled drug/photothermal agent for cancer therapy. Here, we proposed a versatile strategy to create self-assembled chemo-photothermal therapy nanoplatform based on the chemical modification of photothermal agent and drug. The IR-780 and camptothecin (CPT) were chosen as the studied models since they are important photothermal agent and anticancer drug, both of which have such poor water solubility with strong itself molecular interactions that they cannot co-assemble together. IR-780 was modified with an active targeting ligand lactobionic acid (LA) to result in amphiphilic IR780-LA while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through a disulfide linkage to realize its assembly. Well-defined nanoparticles (NPs) could be created through the co-assembling of IR780-LA and CPT-ss-CPT. The IR780-LA/CPT-ss-CPT nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive and enhanced synergistic chemo-photothermal therapy nanoplatform against tumors. Specifically, our chemical modification strategy offers a universal way to create self-assembled chemo-photothermal therapy nanoplatform, which solves the bottleneck of co-assembled drug/photothermal agent for cancer therapy. Statement of Significance Self-assembled nanoparticles of chemotherapeutics with photothermic drugs are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most drugs have too poor solubility and interactions to form into self-assembled nanoparticles. We proposed a versatile strategy to create co-assembled chemo-photothermal therapy nanoparticles based on the chemical modification of common drugs. The IR-780 was modified with an active targeting ligand LA to result in amphiphilic IR780-LA molecules, while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through disulfide linkage. Well-defined IR780-LA/CPT-ss-CPT nanoparticles were created through the co-assembling of IR780-LA and CPT-ss-CPT. The nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive, active targeting chemo-photothermal therapy nanoplatform against tumors. Our strategy offers a versatile way to construct smart chemo-photothermal therapy nanoplatform from common drugs.
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Ke Ma,Jingtao Shi,Yuxin Pei,Zhichao Pei
Most carrier-based nano drug delivery systems (nano-DDSs) are subjected to complex preparation or purification processes, metabolic instability and potential systemic toxicity. To overcome these issues, it is urgent to develop a multifunctional carrier-free nano-DDS that can be fabricated by a simple approach for enhanced anticancer efficacy. In this work, the carrier-free supramolecular nanoprodrug (CF SNPD) based on lactose (Lac) functionalized dimeric camptothecin (CPT) was developed, in which Lac and CPT were conjugated by the aromatized thioacetal (ATA, a reactive oxygen species (ROS)-responsive bond). The obtained Lac-ATA-CPT 2 prodrug and the photosensitizer Chlorin e6 (Ce6) formed CF SNPD (denoted as [email protected] 2 NPs) in water by supramolecular self-assembly. The design of dimeric CPT endowed [email protected] 2 NPs with ultrahigh drug-loading capacity (up to 94%) and excellent stability. The Lac-functionalized CF SNPD displayed active specific targetability to HepG2 cells resulting from the carbohydrate-protein interactions. Furthermore, the fluorescence signal of Ce6 facilitated the precise tracking and localization of [email protected] 2 NPs within the cell. Meanwhile, the ROS generated by Ce6 not only cleaved ATA linker to trigger on-demand CPT release, but also exhibited a killing effect on tumor cells, enabling synergistic therapy via CPT-mediated chemotherapy (CT) and Ce6-induced photodynamic therapy (PDT). Therefore, the multifunctional CF SNPD may be one of the promising therapeutic options for liver cancer.
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Yin-Peng Bai,Cheng-Jie Yang,Nan Deng,Mi Zhang,Zhi-Jun Zhang,Lei Li,Yong Zhou,Xiong-Fei Luo,Chuan-Rui Xu,Bao-Qi Zhang,Yue Ma,Ying-Qian Liu
A series of new 7-ethyl-10-fluoro-20-O-(cinnamic acid ester)-camptothecin derivatives were synthesized and evaluated for cytotoxicity against four human tumor cell lines including HepG2 (hepatocellular carcinoma), SW480 (colorectal cancer), A2780 (ovarian cancer), and Hucct1 (intrahepatic cholangiocarcinoma). The results of cytotoxic activities in vitro showed that most of the camptothecin derivatives harbor promising cytotoxic activity against tested tumor cell lines. Among them, compound XJS-11 exhibited broad-spectrum inhibitory activities against HepG2, SW480, A2780, and Hucct1 cell lines with IC 50 values of 0.03, 0.09, 0.22, and 0.32 μM, respectively. Further investigation demonstrated that compound XJS-11 exhibited more effective growth inhibition against a variety of human hepatoma cells (Sk-hep-1, Hep3B and Huh7) and lower cytotoxicity against immortalized normal human liver cell line L02 than the positive control topotecan . Especially, XJS-11 showed higher selective toxicity in two kinds of human hepatoma cells and immortalized normal human liver cell line (IC 50(L-02) /IC 50(HepG2) = 113.20; IC 50(L-02) /IC 50(Hep3B) = 85.60) than topotecan (IC 50(L-02) /IC 50(HepG2) = 9.45; IC 50(L-02) /IC 50(Hep3B) = 8.52). Mechanistically, XJS-11 induced cell cycle arrest and cell apoptosis in HepG2 and Hep3B cells by inhibiting Top I activity in a manner similar to that of topotecan. Meanwhile, XJS-11 could attenuate the tumor growth in both xenograft and primary HCC mouse models. In addition, the acute toxicity assay showed that XJS-11 did not cause lethality or significant body weight loss with a single intraperitoneal dose at 100 mg/kg or with an intraperitoneal dose at 25 mg/kg for 7 days. Moreover, unlike topotecan, XJS-11 had no apparent toxicity to the mouse liver, kidney, and hemopoietic system of the C57BL/6 mice. Taken together, XJS-11 merits further development as a new generation of the camptothecin-derived drug candidate.
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DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 4
·815
·
IF 3.06
Zhaoxia Jin,Ruyi Wan,Ruxue Yan,Yingying Su,Honglan Huang,Lihan Zi,Fang Yu
Camptothecin (CPT) has strong antitumor activity and is used as an anticancer therapeutic agent. To better understand and decipher the pathway of CPT biosynthesis inCamptotheca acuminata, the main purpose here was focused on creating an effective extraction strategy for a rich intermediate metabolite profile. In the present study, a 70% aqueous acetonitrile was verified as an optimal extraction solvent for microwave-assisted extraction (MAE) of metabolites by spiking experiments. Based on multi-objective optimization, the best extraction conditions of a solid-liquid ratio of 1:20, microwave power of 230 W, and a time of 4 min were achieved using a full factorial 34experimental design. Crude extracts obtained from the shoot apex ofC. acuminatausing MAE have been qualitatively profiled by high-performance liquid chromatography coupled with linear ion trap quadrupole-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap-MS/MS) and a HPLC triple quadrupole-MS (HPLC-TSQ-MS) analysis was conducted for their metabolite content in different tissues. CPT, and ten related metabolites and their isomers, including tryptamine, loganic acid, secologanic acid, strictosidinic acid, strictosamide, strictosamide epoxide, strictosamide diol, strictosamide ketolactam, pumiloside, and deoxypumiloside, were detected and tentatively identified. Scanning electron microscopy (SEM) imaging of the shoot apex demonstrated that severe cell disruption was evident after intensified extraction processes. The study showed the difference of metabolite profiles and the enhancement of metabolite content after microwave-pretreated techniques, and the established MAE procedure is an effective methodology to preserve valuable metabolite compounds for analysis.Keywords:microwave assisted extraction;Taguchi experimental design;metabolites;camptothecin;HPLC-LTQ-MS/MS
研究领域:
植物化学
·
药物化学
·
分析化学
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DOI
PubMed
高影响因子
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