RSC Advances
·
2017
·Vol. 7
·期 20
·12185-12193
·
IF 3.108
Yuhua Zhang,Keming Jiang,Degang Qing,Bing Huang,Jiayi Jiang,Shumei Wang,Chunyan Yan
Camptotheca acuminata Decne (Nyssaceae) is a major natural source of the anticancer drug camptothecin (CPT) and its derivatives. The leaves and stems are two of the main regions that accumulate CPT in C. acuminata. In this study, we successfully isolated cambial meristematic cells (CMCs) and dedifferentiated cells (DDCs) from C. acuminata stems and leaves, identified their characteristic features using micrograph analysis, and assessed their hypersensitivity to γ-irradiation and zeocin. The growth and kinetics curves of CMCs and DDCs were also studied. Furthermore, the accumulation of CPT and 10-hydroxycamptothecin (HCPT)—a more potent and less toxic CPT derivative—was assessed by liquid chromatography, and the transcriptional levels of nine genes encoding key enzymes involved in CPT and HCPT biosynthesis was assessed using quantitative real-time polymerase chain reaction (PCR) in CMCs and DDCs. The results showed that CMCs induced were particularly hypersensitive to γ-irradiation and zeocin and presented with abundant and small vacuoles, whereas DDCs were not. The above morphological and physiological characteristics of CMCs were consistent with previous reports. B5 medium was determined as the best growth medium for CMCs and DDCs. The accumulation of CPT and HCPT was higher in CMCs than DDCs, and the expression of IPI, G10H, ASA1, TSB, TDC1, TDC2, and STR was significantly upregulated in CMCs compared with DDCs; HMGR2 and HMGR3 were downregulated in CMCs. We speculate that the high accumulation of CPT and HCPT in CMCs was due to the upregulation of these seven genes.
研究领域:
药理学
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植物生物学
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分子生物学
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产品关联
DOI
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2025
·
IF 6.2
Tengteng Yang,Wenquan Wang,Xiaoli Wang,Qiaowei Miao,Junhai Liu,Hansheng Wang,Lun Liu,Xiaohui Ji,Chenyang Wei
Camptothecin (CPT) has significant biological activity and has been extensively studied. This study established an efficient and green ultrasonic-assisted deep eutectic solvent (UAE-DES) and combined it with macroporous resin purification technology to extract and purify CPT and 10-hydroxycamptothecin (HCPT) from Camptotheca acuminata fruit. In total, 33 natural DES were prepared, among which choline chloride-1,4-butanediol was the most effective. The single-factor and response surface optimization extraction experiments were carried out to determine optimal conditions as follows: ultrasonic time = 27 min, solid-liquid ratio = 1:35 g/mL, ultrasonic temperature = 70 °C, DES moisture content, = 29 %, and total extraction rate = 0.1318 %. Furthermore, the scanning electron microscopy revealed that the UAE-DES treatment significantly disrupted the cell-wall structure of C. acuminata fruits, promoting the release of the target constituents. Moreover, AB-8-type macroporous resin was employed to optimize adsorption and desorption, which optimized 63.4 % and 77.3 % adsorption and desorption of CPT and HCPT, respectively. Density functional theory (DFT) was employed for assessing electrostatic potential (ESP), complexation energy, and reduced density gradient (RDG), to identify the non-covalent interactions between DES, conventional solvent ethanol, and CPT-like compounds during the extraction process. This study comprehensively explained the extraction mechanism and confirmed that DES had better extraction potential and good biocompatibility. These findings provide a theoretical basis and technical support for the green and efficient extraction and purification of CPT-like compounds.
研究领域:
天然产物化学
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药物分析
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植物药学
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绿色化学
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分子互作机制
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Wenyan Guo,Yi Yang,Guangyuan Liu,Jiaojiao Zhao,Yuyu Zhang,Yahui Li,Bingkun Yang,Xiaoque Zhu,Dandan Li,Xia Qin,Panpan Zhang,Zuxiao Yang,Wei Guo,Dezhi Kong,Wei Zhang
Ethnopharmacological relevance Cepharanthine (CEP) is an alkaloid extracted from Stephania cephalantha Hayata, a traditional Chinese medicine (TCM) renowned for its heatclearing and dehumidifying properties. For centuries, Stephania cephalantha Hayata has been employed in the treatment of a wide range of diseases, including pain, edema, inflammation, and fever. Aim of the study Our research aims to investigate the role and mechanism of Cepharanthine in ameliorating uric acid (UA) induced neuroinflammatory responses. Materials and methods The Connectivity Map (CMap) was utilized to identify the therapeutic drug Cepharanthine, based on the proteomic disturbances associated with uric acid (UA). Limited proteolysis small molecule mapping (LiP-SMap) and thermal proteome profiling (TPP) technologies were used to identify the direct target proteins for UA and Cepharanthine. Additionally, we used the induced-fit docking algorithm integrated within the Schrodinger suite to explore the interactions between Cepharanthine and uric acid targets. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to determine the concentration of Cepharanthine in the mice cerebral cortex. The pro-inflammatory cytokine genes were also quantified by qPCR in U251 cells and in hyperuricemic mice. Results The findings indicated that uric acid increased the transcription of pro-inflammatory cytokines and the expression levels of proteins linked to inflammation in U251 cells. PPP2R1A was identified as a potential candidate for direct interaction with uric acid, potentially initiating inflammation. Based on the CMap prediction, Cepharanthine was identified as a candidate drug for interaction with PPP2R1A. TPP analysis indicated that Cepharanthine could reduce the thermal stability of PPP2R1A. Molecular docking confirmed that Cepharanthine could directly bind to PPP2R1A. Furthermore, the detection of Cepharanthine in the cerebral cortex suggested its ability to cross the blood-brain barrier. Proteomic analysis of Cepharanthine-treated mice revealed significant enrichments of differentially expressed proteins (DEPs) in inflammation-related pathways and biological processes. Additionally, Cepharanthine was effective in decreasing the expression of pro-inflammatory cytokine genes induced by uric acid in U251 cells and in hyperuricemic mice. Conclusion Cepharanthine could effectively alleviate hyperuricemia-induced neuroinflammation via binding to PPP2R1A. This study offers a novel approach for prevention and treatment of neurological diseases caused by hyperuricemia.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2019
·Vol. 20
·期 8
·1961
·
IF 4.183
Bing Yu,Qingye Meng,Hao Hu,Tao Xu,Youqing Shen,Hailin Cong
Polymeric micelles (PMs) have been applied widely to transport hydrophobic drugs to tumor sites for cancer treatment. However, the low load efficiency of the drug in the PMs significantly reduces the therapeutic efficiency. We report here that disulfide-linked camptothecin (CPT) as a kind of dimeric drug can be effectively embedded in the core of poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) PMs for improving drug-loading efficiency, and PEG can be used as a hydrophilic shell. Moreover, the dimeric CPT-loaded PCL–PEG–PCL PMs exhibited excellent solubility in phosphate-buffered saline (PBS) media and significant cytotoxicity to cancer cells.Keywords:dimeric drug;camptothecin;micelles;cancer therapy
研究领域:
药学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2014
·
IF 2.129
Linlin Wang,Yizhong Shen,Shaopu Liu,Jidong Yang,Wanjun Liang,Dan Li,Youqiu He
The interactions of topotecan hydrochloride (THC), neutral red (NR) and thioglycolic acid (TGA) capped CdTe/CdS quantum dots (QDs) built a solid base for the controlling of the fluorescent reversible regulation of the system. This study was developed by means of ultraviolet–visible (UV–vis) absorption, fluorescence (FL), resonance Rayleigh scattering (RRS) spectroscopy and transmission electron microscopy (TEM). Corresponding experimental results revealed that the fluorescence of TGA-CdTe/CdS QDs could be effectively quenched by NR, while the RRS of the QDs enhanced gradually with the each increment of NR concentration. After the addition of THC, the strong covalent conjugation between NR and THC which was in carboxylate state enabled NR to be dissociated from the surface of TGA-CdTe/CdS QDs to form more stable complex with THC, thereby enhancing the fluorescence of the TGA-CdTe/CdS QDs-NR system. What is more, through analyzing the optical properties and experimental data of the reaction between TGA-CdTe/CdS QDs and NR, the possible reaction mechanism of the whole system was discussed. This combination of multiple spectroscopic techniques could contribute to the investigation for the fluorescent reversible regulation of QDs and a method could also be established to research the interactions between camptothecin drugs and dyes.
研究领域:
药理学
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纳米生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2021
·
IF 8.109
R. Sun,Q. Luo,X. Li,X. Huang,L. Teng,Z. Shen,W. Zhu
PEGylated drugs and their self-assembled nanoparticles have been used as a first-line technology in nanomedicines . However, premature disassembly before reaching the lesions under dilute conditions limits their bioavailability. This challenge can be overcome by covalent crosslinking. However, undefined molecular structures of the prodrugs are introduced, which hinder large-scale production and clinical translation. Herein, a supramolecular PEGylated camptothecin nanodrug with a crosslinked architecture and defined molecular drug structure was developed. PEGylated mono-tetraethylenepentamine β-cyclodextrin (mPEG-TEPA-CD) and adamantane modified camptothecin (AD-SS-CPT) were first synthesized. The host-guest coupling of β-cyclodextrin (β-CD) and adamantine (AD) moieties between mPEG-TEPA-CD and AD-SS-CPT induced the formation of supramolecular PEGylated camptothecin, which could self-assemble into micelles in the aqueous medium. They were further stabilized by the addition of a diacrylate crosslinker for reaction with the amine groups on mPEG-TEPA-CD, maintaining the unaltered AD-SS-CPT. The nanodrugs can internalize into tumor cells quickly and release free camptothecin in response to glutathione . They also have prolonged blood circulation time and can accumulate efficiently at tumor sites, thus showing effective antitumor activity . This supramolecular drug delivery system provides a new strategy for the design of nanodrugs.
研究领域:
药学
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纳米医学
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肿瘤学
✓ 已验证
DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2013
·Vol. 97
·期 21
·9365-9375
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IF 3.689
Pu Xiang,Qu Xixing,Chen Fei,Bao Jinku,Zhang Guolin,Luo Yinggang
Camptothecin (CPT), the third largest anticancer drug, is produced mainly by Camptotheca acuminata and Nothapodytes foetida . CPT itself is the starting material for clinical CPT-type drugs, but the plant-derived CPT cannot support the heavy demand from the global market. Research efforts have been made to identify novel sources for CPT. In this study, three CPT-producing endophytic fungi, Aspergillus sp. LY341, Aspergillus sp. LY355, and Trichoderma atroviride LY357, were isolated and identified from C. acuminata . Most CPT produced by these fungi was found in the fermentation broth, and their corresponding CPT yields were 7.93, 42.92, and 197.82 μg l −1 , respectively. The CPT-producing capability of LY341 and LY355 was completely lost after repeat subculturing. A substantial decrease of CPT production was also observed in the second generation of LY357. However, a stable and sustainable production of CPT was found from the second generation through the eighth generation of LY357. The fermentation medium, time, pH, temperature, and agitation rate were optimized for CPT production. Methyl jasmonate and XAD16 were proven to be an optimum elicitor and adsorbent resin, respectively, in view of that CPT yield was increased 3.4- and 11-fold through their use. A 50- to 75-fold increase of CPT yield was obtained when the optimized fermentation conditions, elicitor, and adsorbent resin were combined and applied to the culture of the seventh and eighth generations of LY357, and the highest CPT yield was 142.15 μg l −1 . The CPT-producing T. atroviride LY357 paves a potential to uncover the mysteries of CPT biosynthesis.
研究领域:
药用植物学
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微生物学
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药物开发
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Zhichao Wang,Qingyong Li,Xiuhua Zhao,Baihe Sun,Qiaochu Zhu,Wenqing Gao,Changlong Hua
The purpose of this work is to prepare a formulation using mannitol coupling Camptothecin (CPT) nanoparticles (CPT-NPs) to circumvent the difficult solubilization practice based on central composite experimental statistical design. CPT-NPs were prepared with a high-pressure homogenization technique method. The independent variables considered for the optimization of CPT-NPs were percentage of CPT in raw material (CPT and mannitol), concentration of CPT in working liquid, cycles numbers and homogenizer pressure for drug loading efficiency, particle size and polydispersity index. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized CPT-NPs showed an appropriate drug loading efficiency (18.09 ± 2.13%), a homogeneous particle size (165.33 ± 37.23 nm) and a low polydispersity index (0.29 ± 0.01). The CPT-NPs group show higher inhibition ratio (79.95%) of H22 tumor growth in vivo compared with TPT and CPT at the same dose. Changes in mice body weight demonstrate CPT-NPs have the lower toxicity. The results of biodistribution studies indicated the obviously superiority of CPT-NPs in increasing the accumulation of CPT within tumor. Overall, CPT-NPs under optimum conditions are considered to be potentially feasible to overcome formulation challenges for drug delivery.
研究领域:
药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 9
·5094-5102
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IF 7.79
Jing Liu,Can Wu,Guoru Dai,Feng Feng,Yuquan Chi,Keming Xu,Wenying Zhong
Tyroservatide (YSV) belongs to a class of bioactive peptides that have drawn considerable attention in the field of drug discovery, yet it displays limited potency and often requires a millimolar concentration to execute its cellular functions. To enhance the potency of the drug through a self-assembling strategy, we designed and synthesized a series of octapeptides through conjugation of YSV with a pentapeptide sequence bearing alternating hydrophobic and hydrophilic amino acids to promote their self-assembling capabilities. Initial screening for hydrogelation gave a novel octapeptide (denoted as 1-YSV hereafter) that was capable of self-assembling under physiological conditions to afford supramolecular nanofibers with enhanced anti-cancer efficacy compared to YSV itself. Interestingly, 1-YSV formed a robust co-assembly with the anticancer drug hydroxycamptothecin (HCPT) to afford 1-YSV/HCPT hydrogel, which not only greatly improved the viscoelastic properties of hydrogels, but also stabilized HCPT in the hydrogel matrix and avoided the agglomeration of drug molecules. Compared to HCPT solution, the hydrogel formulation of 1-YSV/HCPT demonstrated better efficacy against the proliferation of non-small cell lung cancer A549 cells both in vitro and in vivo. Finally, thanks to the pure amino acid-based composition, the 1-YSV/HCPT formulation exhibited excellent biocompatibility, giving a low hemolytic rate to red blood cells, with mild local tissue reactions and negligible systematic toxicities in mice.
研究领域:
药学
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生物材料学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Ran Hao,Meng Jiao,Xingguo Xu,Di Wu,Haiying Wei,Leyong Zeng
Delivery nanosystems were popularly developed to improve chemotherapy efficacy, but the non-specific leakage of drugs was still not satisfactory. Here, using gold nanocages (AuNCs) as carrier and thermo-sensitive liposome (TSL) as protection shell, a camptothecin (CPT) loaded delivery nanosystem (AuNCs/CPT@TSL) was designed for photothermal-modulated drug release, by which the non-specific leakage of CPT was avoided, and the combination of photothermal therapy (PTT) and chemotherapy was achieved. In the simulated tumor microenvironment (pH=5.5), the TSL shell protected CPT from leakage at 37℃, and the release rate of CPT was only 11.4%. However, the release rate of CPT greatly increased to 85.4% by elevating temperature to 45℃. The photothermal conversion efficiency of AuNCs/CPT@TSL reached up to 46.1%. When the incubation temperature was 37℃, the cell survival rate was reduced to 43.6% in AuNCs/CPT, but was still above 90% in AuNCs/CPT@TSL, demonstrating the good protection of TSL shell. Under the combination of PTT/chemotherapy, the cell viability greatly decreased to 10.9%, and the tumors completely disappeared, confirming the safe and reliable antitumor effect of AuNCs/CPT@TSL.
研究领域:
纳米医学
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肿瘤学
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药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 8
·3277-3286
·
IF 5.251
Jun Li,Zu-E. Hu,Xian-Ling Yang,Wan-Xia Wu,Xiu Xing,Bo Gu,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
Dual stimuli-responsive camptothecin polymeric prodrugs (CPT Prodrugs) with grafted structures were designed via chemoenzymatic methods and combined with doxorubicin (DOX) for synergistic drug delivery to improve anticancer efficiency. The CPT Prodrugs loaded DOX with a high efficiency through the cooperative contribution of several interaction forces. The produced amphiphilic polymeric prodrugs loaded with DOX, referred to as DOX@CPT Prodrugs, formed homogeneous spherical micelles of appropriate sizes (sub-50 nm). The DOX@CPT Prodrug micelles showed excellent stability in release experiments under in vitro physiological conditions and maintained over 80% drug loading after 4 weeks when stored at 4 °C. Under weakly acidic pH and reduced glutathione (GSH) conditions, the DOX@CPT Prodrugs with high disulfide and tertiary amine content achieved synergistic release of the two loaded drugs and biodegraded into low-molecular-weight compounds. The cell experiments confirmed that the internalization of DOX@CPT Prodrugs into cancer cells was greatly improved by nearly 30% compared with that of free drugs. Furthermore, the synergistic drug delivery system exhibited superior anticancer efficiency with highly improved cell selectivity ratios (up to 127.0%) and greatly enhanced synergistic effects (up to 23.9%) benefiting from good long-term stability, better internalization by cells and sensitive pH and GSH dual-responsivity. In addition, the DOX@CPT Prodrugs with suitable sizes and good water solubility also exhibited a greater penetrability in the case of simulating solid tumors than the free drugs. These results demonstrate the potential of DOX@CPT Prodrugs as biodegradable, dual-responsive combination therapy nanocarriers for synergistic anticancer treatment.
研究领域:
药学
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肿瘤学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2014
·
IF 1.357
Yan-Ling Luo,Jing-Yu Fu,Feng Xu,Ya-Shao Chen,Bin Zhang
Thermo-sensitive poly(N-isoproplacrylamide)m-block-hydroxyl-terminated polybutadiene-block-poly(N-isoproplacrylamide)m (PNIPAMm-b-HTPB-b-PNIPAMm, m = 1 or 2) block copolymers, AB4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with HTPB as central blocks, and characterization was performed by 1H NMR, Fourier transform infrared, and size exclusion chromatography. The multiblock copolymers could spontaneously assemble into more regular spherical core–shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension, nanoparticle analyzer, transmission electron microscope (TEM), dynamic light scattering, and UV–vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm, and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature of about 33–35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks, and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles.
研究领域:
高分子化学
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药物递送系统
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生物材料
✓ 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）