Insect Science
·
2025
·
IF 3
Yi Ding,Yuntian Cui,Huijie Xie,Jinhui Liang,Huan Liu,Fenghou Yuan,Tian Liu
The mode of action of botanical pesticides is often complex. In this study, camptothecin (CPT), a plant-derived compound, was found to alter the mechanical properties of the cuticle in the lepidopteran pest, Ostrinia furnacalis . CPT treatment resulted in a thinner, distorted cuticle with significantly reduced pigmentation. Fourier transformed infrared spectroscopy indicated decreased tyrosine-mediated crosslinking and melanin formation, while metabolomics showed a significant reduction in N -acetyldopamine content, with no reduction in dopamine or related precursors. Despite a slight increase in laccase 2 transcript levels, laccase activity was significantly reduced in CPT-fed larvae, suggesting that CPT may inhibit laccase translation or zymogen activation. This reduction in laccase activity led to impaired sclerotization and pigmentation, producing a disordered cuticle with weakened mechanical properties. These findings provide new insights into the mode of action of botanical pesticides and their potential to regulate insect cuticle formation.
研究领域:
昆虫学
·
植物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED RADIATION AND ISOTOPES
·
2012
·
IF 1.172
Zhen-feng Liu,Guo-lin Wang,Meng-jie Dong,Qian Zhang,Jia-jun Li,Kui Zhao,Shu-ye Yang,Xiang-tong Lin
10-[ 11 C]methoxy-20(S)-camptothecin was synthesized automatically. The radiochemical yield was 30%–50% (all calculated at EOB, n =20) with [ 11 C]methyl triflate as a methylating agent. The radiochemical purity was greater than 96%, and the specific activity was 8.72±2.18 GBq/μmoL at EOS . Biodistribution showed that 10-[ 11 C]methoxy-20(S)-camptothecin is characterized by quick clearance from the blood and by significant uptake in the liver (5.72±1.92% ID/g at 15 min), intestines (2.43±0.38% ID/g at 15 min), and kidney (1.57±0.85% ID/g at 15 min). Micro-PET imaging clearly showed high radioactivity accumulation in liver, intestines and bladder, indicating that the primary modes of excretion of the radiotracer are through the hepatobiliary system and, to a lesser extent, through the renal system.
研究领域:
药理学
·
核医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
·
IF 4.787
Chaoyu Liu,Jiang Yuan,Xiaoming Luo,Maohua Chen,Zhoujiang Chen,Yuancong Zhao,Xiaohong Li
It is one of the challenges for a wide clinical application of polymer micelles to address the structure disintegration and premature drug release before reaching a pathological site. In the current study, folic acid (FA)-decorated polymer–drug conjugates (FSC) were synthesized with disulfide linkages between camptothecin (CPT) and amphiphilic poly(ethylene glycol)-b-poly(ε-caprolactone) (PECL) copolymers. FSC conjugates were proposed to assemble into micelles with a hydrophobic core of PCL segments and CPT and a hydrophilic corona of PEG segments. The addition of hexadecanol during micelle formation (FSC-16) was proposed to modulate the interactions of hydrophobic segments in micelles and enhance the reductive sensitivity. FSC-16 micelles were obtained with critical micelle concentration of around 2 μg/mL and an average size of around 200 nm, and the conjugated CPT was rapidly released out in response to glutathione. The reductive sensitivity was also demonstrated with respect to the changes of micelle size and morphologies as well as the fluorescent intensity of pyrene loaded in micelles. Benefiting from the FA receptor-mediated uptake and the reduction-sensitive release of CPT, significant cytotoxicity and cell apoptosis were identified for FSC-16 micelles against SKOV-3 cells with strong expressions of FA receptors. Flow cytometry and confocal laser scanning microscopy analyses demonstrated that CPT was distributed into nuclei after cellular uptake and intracellular release from FSC-16 micelles. Thus, the FA-decorated and reduction-sensitive micelles assembled from polymer–drug conjugates show advantages in inhibiting premature release during circulation, enhancing cellular uptake at the tumor tissues, and promoting intracellular release and nuclei location of the active moieties.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 21
·10277-10287
·
IF 7.233
Chun Tian,Jinyun Niu,Xuerui Wei,Yujie Xu,Lifen Zhang,Zhenping Cheng,Xiulin Zhu
The performance of functional polymer nanomaterials is a vigorously discussed topic in polymer science. We devoted ourselves to investigating polymer nanomaterials based on near-infrared (NIR) fluorescence imaging and polymer prodrug in this study. Aza-boron dipyrromethene (BODIPY) is an important organic dye, having characteristics such as environmental resistance, light resistance, high molar extinction coefficient, and fluorescence quantum yield. We incorporated it into our target monomer, which can be polymerized without changing its parent structure in a polar solvent and copolymerized with water-soluble monomer to improve the solubility of the dye in an aqueous solution. At the same time, the hydrophobic drug camptothecin (CPT) was designed as a prodrug monomer, and the polymeric nanoparticles (NPs) with NIR fluorescence imaging and prodrug were synthesized in situ in reversible addition–fragmentation chain transfer (RAFT)-mediated aqueous dispersion polymerization. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed the final uniform size of the dual-functional polymeric NPs morphology. The dual-functional polymeric NPs had a strong absorption and emission signal in the NIR region (>650 nm) based on the fluorescence tests. In consideration of the long-term biological toxicity, confocal laser scanning microscopy (CLSM) results indicated that the dual-functional NPs with controlled drug content exhibited effective capability of killing HeLa cells. In addition, in vivo imaging of the dual-functional NPs was observed in real time, and the fluorescent signals clearly demonstrated the dynamic process of prodrug transfer.
研究领域:
高分子科学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2013
·Vol. 130
·期 6
·4137-4146
·
IF 1.395
Yan-Ling Luo,Xiao-Li Yang,Feng Xu,Ya-Shao Chen,Zhuo-Ma Ren-Ting
A novel A 2 BA 2 -type thermosensitive four-armed star block copolymer, poly( N -isopropyl acrylamide) 2 - b -poly(lactic acid)- b -poly( N -isopropyl acrylamide) 2 , was synthesized by atom transfer radical polymerization and characterized by 1 H-NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography. The copolymers can self-assemble into nanoscale spherical core–shell micelles. Dynamic light scattering, surface tension, and ultraviolet–visible determination revealed that the micelles had hydrodynamic diameters ( D h ) below 200 nm, critical micelle concentrations from 50 to 55 mg/L, ζ potentials from −7 to −19 mV, and cloud points (CPs) of 34–36°C, depending on the [Monomer]/[Macroinitiator] ratios. The CPs and ζ potential absolute values were slightly decreased in simulated physiological media, whereas D h increased somewhat. The hydrophobic camptothecin (CPT) was entrapped in polymer micelles to investigate the thermo-induced drug release. The stability of the CPT-loaded micelles was evaluated by changes in the CPT contents loaded in the micelles and micellar sizes. The MTT cell viability was used to validate the biocompatibility of the developed copolymer micelle aggregates. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4137–4146, 2013
研究领域:
材料科学
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2013
·Vol. 97
·期 21
·9365-9375
·
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
·
微生物学
·
药物开发
✓ 已验证
DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2019
·
IF 5.107
Ting Wang,Pengfei Li,Yao Sun,Xiaomei Song,Hao Li,Liting Qin,Juying Zhou,Qin Huang,Fuhou Lei
In this work, camptothecin (CPT) molecularly imprinted polymer (MIP) microspheres were prepared via membrane emulsification-suspension polymerization using ethylene glycol maleic rosinate acrylate as a crosslinker, acrylic acid as a functional monomer, and CPT as a template molecule. The MIPs were characterized by scanning electron microscopy, laser granulometry, nitrogen sorption porosimetry, and thermogravimetric analysis. The results indicated that the MIPs had a regular spherical shape with porous surfaces and particle sizes mainly ranging from 3 to 5 μm. The surface areas of the MIPs and non-molecularly imprinted polymer (NIP) microspheres were 89.44 and 86.91 m 2 g −1 , respectively, and their respective average pore sizes were 11.42 and 10.84 nm. Furthermore, the MIPs and NIPs exhibited excellent thermal stabilities. The HPLC columns prepared with the MIPs and NIPs as the chromatographic stationary phase showed good fluidity. The effect of the MIP column on CPT was evaluated with HPLC, and the selectivity and separation performance of the MIP and NIP columns for CPT and 10-hydroxycamptothecin were evaluated. The chromatographic thermodynamics and separation mechanism were also studied. Finally, the MIP column was successfully applied to the separation and purification of CPT from an extract of Camptotheca acuminata fruit, and the reusability of the MIP column was also investigated.
研究领域:
药学
·
分离科学
·
材料科学
✓ 已验证
产品关联
DOI
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
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
高影响因子
POLYMER
·
2010
·
IF 3.573
Honglei Fan,Jin Huang,Yaping Li,Jiahui Yu,Jinghua Chen
This research is aimed to develop a reduction-degradable micelle delivery system based on polymer-camptothecin (CPT) conjugate in order to enhance the solubility and stability of CPT in aqueous media. Firstly, disulfide-linked poly(amido amine) (SS-PAA) containing alkyne groups was synthesized by Michael addition polymerization between propargyl amine and N , N ′-bis(acryloyl) cystamine (BAC). And then, azide-functionalized CPT derivatives were conjugated with SS-PAA by click cycloaddition. Further grafting of residual alkyne groups in SS-PAA with azide-terminated poly(ethylene glycol) methyl ether (mPEG) gave mPEG- g -SS-PAA-CPT conjugate. At last, micelles with size of ca. 88 nm were fabricated from mPEG- g -SS-PAA-CPT conjugate, suggesting their passive targeting potential to tumor tissue. It was worthy of note that the drug-loaded system of mPEG- g -SS-PAA-CPT micelles improved the solubility and stability of CPT in aqueous media. Owing to the reduction degradability of disulfide linker in main chain of mPEG- g -SS-PAA-CPT, the CPT sustainably release from micelles together with the gradual cleavage of polymer in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition while almost no change occurred at the level of DTT corresponding to extracellular condition. Furthermore, the cell viability results showed the essential decrease of cytotoxicity to L929 cell line. These results present a strategy in designing anti-tumor CPT-polymer conjugates for highly selective delivery to tumor cells.
研究领域:
药学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yefeng He,Siqi He,Hongji Wang,Xiaoyu Li,Liying Cui,Zhongkai Liu,Shengkai Liu,Xiaoshuai Wang,Mengqi Liu,Yujie Fu,Zhiguo Liu
Cyclodextrin-based metal-organic frameworks (γ-CD-MOFs) are promising biocompatible nanocarrier. However, it faces the problem of poor stability in aqueous solution. This study explores camptothecin delivery using a natural polymer-based shell (chitosan/carboxylated cellulose nanofibers) modified γ-CD-MOF core, establishing a novel strategy for safe and efficient CPT delivery. The γ-CD hydrophobic cavities significantly enhance CPT solubility and loading. The fabricated nanocarrier achieve CPT loading and encapsulation efficiencies of 26.4 ± 2.52 % and 70.2 ± 2.88 % respectively. Furthermore, the CPT load nanocarrier demonstrate <5 % hemolysis at the concentration of 800 μg/mL, exhibit drug release behavior conforming to the Higuchi equation, and show significant antiproliferative effects against MDA-MB-231 cells.
研究领域:
药剂学
·
纳米技术
·
材料科学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
·
植物生物学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOCONJUGATE CHEMISTRY
·
2024
·
IF 4
Yang Tao,Maoxin Du,Meihua Zhu,Yinyue Wang,Yusong Fei,Yu-Qiang Zhao,Junjie Ma,Ruifeng Fan,Fang Dai,Jingchao Chen,Junlin Yin,Baomin Fan,Guangzhi Zeng
The peptide–drug conjugate (PDC) has emerged as one of the new approaches for cancer therapy, which has the advantages of improved drug target ability and reduced adverse effects compared with the traditional chemotherapy. CD133 is a surface antigen specific to cancer stem cells, which are thought to be responsible for the self-renewal, proliferation, metastasis, and chemoresistance of cancer cells. A PDC for CD133 was designed by us, and it consists of CD133 targeting peptide LS-7 (amino acid sequence LQNAPRS), a pH-sensitive linker (succinyl), and a cytotoxic payload, the cytotoxic molecule camptothecin (CPT) with potent toxicity in vivo and in vitro. An antitumor study exhibited that the conjugate LS-7-CPT has not only improved its cytotoxicity in tumor cells but also retained its anticancer effect in vivo. In addition, the acute toxicity in mice of LS-7-CPT has been improved and the maximum tolerated dose has been increased by at least 56.2-fold. Pull-down and in vivo fluorescent imaging results indicated that LS-7-CPT was enriched in mice tumors by targeting CD133 protein. As far as we know, this is the first report for a PDC molecule designed for CD133, which is important for the study of CPT drug development.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
癌症研究
✓ 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）