PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2019
·
IF 2.87
Shu Xu,Bi Wang,Linwei Li,Qian Zhou,Mei Tian,Xingzeng Zhao,Jian Peng,Fei Liu,Yu Chen,Yannan Xu,Xu Feng
Rice blast caused by Magnaporthe oryzae B. Couch is one of the most devastating diseases on rice. Camptothecin (CPT), which was primarily isolated from Camptotheca acuminata , is well-known for its anti-tumor activities, and is also developed as a potential biological pesticide . We previously investigated the anti-microbial activities of CPT against 11 fungi, 3 oomycetes , and 4 bacteria, and found that CPT was strongly effective against M. oryzae , indicating its potential as a lead for developing fungicide against rice blast. However, the anti-fungal effects of CPT on M. oryzae need further elucidation. In this study, the anti-fungal activities of CPT against M. oryzae were further investigated, which revealed that CPT was effective against M. oryzae both in vitro and in vivo . The transcriptome of M. oryzae was analyzed after CPT treatment, which showed that CPT had a strong inhibitory effect on ‘translation’ and ‘carbohydrate metabolism/energy metabolism’ of M. oryzae . Some physiology characteristics of M. oryzae were also assayed, which confirmed that CPT inhibited RNA synthesis , protein synthesis , and carbohydrate metabolism/energy metabolism of M. oryzae , and caused membrane damage. The molecular simulation result showed that CPT binds to the interface of DNA-topoisomerase I complex of M. oryzae . In conclusion, CPT is a promising lead for developing fungicide against rice blast. CPT may bind to DNA-topoisomerase I complex of M. oryzae , thus affecting ‘translation’ and ‘carbohydrate metabolism/energy metabolism’, leading to cell death.
研究领域:
植物病理学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2014
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IF 3.785
Xin-Jiang Tang,Min Han,Bo Yang,You-Qing Shen,Zhong-Gui He,Dong-Hang Xu,Jian-Qing Gao
Camptothecin (CPT) nanosuspension was prepared by anti-solvent precipitation with TPGS as stabilizer to improve the solubility, stability and antitumor activity of CPT. And an increased solubility, stability and dissolution rate was achieved after nanosuspension being prepared. While, enhanced intracellular accumulation and cellular cytotoxicity was also observed for CPT nanosuspension than that of CPT solution.In addition, nanosuspension could increase bioavailability and intratumor accumulation of CPT in vivo after intravenous administration, and then produced a much higher antitumor effect and biocompatibility than that of CPT solution. Meanwhile, an enhanced cellular CPT uptake in hypoxic or acid conditions could also be observed for nanosuspension. As a result, nanosuspension represents a potentially feasible formation for insoluble drug in antitumor research.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
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IF 3.756
Qin Tang,Fangling Ji,Jingyun Wang,Lianying Guo,Yachen Li,Yongming Bao
Quercetin (Qu) is known as a dietary antioxidant with numerous bioactivities, but its function in anti-cancer has not been fully investigated. Here, we show that Qu at low doses (≤ 10 μM) significantly enhances the inhibition of 10-hydroxy camptothecin (HCPT) on the proliferation of MCF7, BGC823 and HepG2 cells. A plasmid DNA relaxation assay indicates that the inhibition of HCPT on the catalytic activity of topoisomerase I (Topo I) is increased by Qu at 10 μM. Compared to the treatment by Qu or HCPT alone, phosphorylation at Ser 139 of γH2A.X in MCF7 cells starts to increase significantly (P < 0.05) at 6 h when treated by the combination of 10 μM Qu and 0.62 μM HCPT. Moreover, the combinational group successively arrests MCF7 cells at G1, S and G2/M phases from 12 h to 48 h via up-regulation of p21 and induces apoptosis at 24 h by triggering intrinsic cell death pathways. In addition, the inhibition effects of the combinational group on the proliferation of MCF7 cells are eliminated by pretreatment with 100 μM Z-VAD-FMK (a caspase inhibitor). Finally, by using nude mice xenografting assay of MCF7 cells, we demonstrate that tumor inhibition rates of combinational group are significantly higher than single-drug group. In summary, the synergic anti-cancer mechanism of Qu and HCPT in MCF7 cells is through the combined inhibitory effects of Qu and HCPT on Topo I, which synergistically induce cell cycle arrest and apoptosis by triggering DNA damage.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 17
·3918-3928
·
IF 5.344
Lu Lu,Bing Li,Chuanchuan Lin,Ke Li,Genhua Liu,Zengzilu Xia,Zhong Luo,Kaiyong Cai
Tumor cell-targeting drug delivery systems are of great importance to anti-tumor therapy in clinics. Owing to the overexpression of the asialoglycoprotein receptor (ASGPR) on the membrane of hepatoma carcinoma cells, the conjugation of lactose on the surface of drug delivery systems has already shown significant advantages for targeting tumor cells. In this study, a disulfide bond-conjugated prodrug targeting delivery system consisting of camptothecin (CPT) and lactose (LA) was synthesized, which was denoted as CPT-S-S-LA. Camptothecin and lactose act as the chemotherapy drug and targeting ligand in the drug delivery system, respectively. Since CPT-S-S-LA is an amphiphilic compound, it can self-assemble into nanoparticles with a diameter of around 110 nm. The CPT-S-S-LA nanoparticles displayed controllable drug release behavior in the physiological environment. Unlike the free CPT, the CPT-S-S-LA nanoparticles firstly assembled at the tumor sites via the enhanced permeability and retention (EPR) effect, and then were phagocytized by the tumor cells with ASGP receptor-mediated endocytosis. Finally, the antitumor agent CPT was released for killing tumor cells, which have a high glutathione (GSH) concentration environment. The nanoparticles displayed favorable ability to target hepatoma carcinoma cells rather than the normal HUVEC cells in vitro. Both the in vitro and in vivo studies demonstrated that the CPT-S-S-LA nanoparticles display enhanced antitumor ability and reduced side effects. Thus, active targeting prodrug delivery systems should be a promising strategy for liver tumor therapy.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
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IF 9
Qian Ao,Han Xu,Song Bo,He Yuchen,Yang Shengxiang
Camptothecin (CPT), a pharmacologically important indole alkaloid, requires efficient and selective separation for pharmaceutical applications. In this study, a novel biochar-based surface molecularly imprinted polymer (CPT/BC-SMIP) was successfully synthesized via optimized free radical polymerization, combining the high surface area, excellent adsorption capacity, and environmental friendliness of biochar with the specificity of surface molecular imprinting technology. Characterization results confirm the formation of well-defined imprinting cavities on the CPT/BC-SMIPs, which exhibit excellent molecular recognition and thermal stability. Adsorption studies reveal that CPT adsorption adheres to pseudo-second-order kinetics, achieving equilibrium within 40 min at 298.15 K, with a maximum adsorption capacity of 82.37 mg·g −1 . Notably, the material maintains over 89 % of its initial adsorption capacity after six consecutive adsorption-desorption cycles, demonstrating outstanding reusability. Selectivity experiments validate the superior recognition capability of CPT/BC-SMIPs for CPT, with an imprinting factor of 2.51, while selectivity factors for structural analogs (10-HCPT, 7-ECPT, EVO, and BBR) are recorded at 2.29, 2.32, 2.87, and 2.81, respectively. In practical applications, the material effectively isolates CPT from Camptotheca fruit extracts, achieving recovery rates between 100.25 % and 107.75 %, with relative standard deviations below 3.24 %, indicating promising practical utility. Overall, this study provides a novel approach for the efficient separation and purification of bioactive compounds from natural products and underscores the promising application of CPT/BC-SMIPs in pharmaceutical separation processes. The material's superior adsorption capacity, selectivity, and stability position it as a strong candidate for industrial-scale CPT purification.
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产品关联
DOI
高影响因子
Nanomedicine
·
2019
·
IF 4.717
Wei He,Yawei Du,Wenya Zhou,Chen Yao,Xinsong Li
Aim: A redox-triggered camptothecin (CPT) liposomal system was developed for an improved clinical potential in tumor therapy. Materials & methods: CPT–phosphorylcholine conjugates (CPT–SS–GPCs: CPT–SS–3–GPC and CPT–SS–11–GPC) were synthesized by conjugating CPT to glycerylphosphorylcholine via disulfide bond linker. CPT–SS–GPCs could be assembled into liposomes. Different in vitro and in vivo analyses were used to evaluate the anticancer activities of CPT–SS–GPCs. Results: CPT–SS–GPCs liposomes exhibited extremely high drug loading and uniform size of 150–200 nm. Moreover, the rapid release of parent CPT in reductive condition and high cellular uptake of CPT–SS–GPCs liposomes were observed. At last, in vitro and in vivo anticancer assay showed the enhanced efficacy of CPT–SS–GPCs liposomes. Conclusion: Redox-triggered CPT–SS–GPC liposomes have great potential in tumor therapy.Graphical abstract
研究领域:
药学
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
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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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Ping Luo,Yu Luo,Jin Huang,Wei Lu,Dajun Luo,Jiahui Yu,Shiyuan Liu
In this research, a reduction-degradable supramolecular micelle delivery system of camptothecin (CPT) was developed to enhance the stability of CPT in aqueous media. Firstly, Michael addition polymerization occurred between N, N ’-bis(acryloyl) cystamine (BAC) and mono(6-(2-aminoethyl)amino-6-deoxy)-β-cyclodextrin (CDen) to produce the reduction-degradable polymer of BAC-CDen. And adamantyl-modified polyethylene glycol monomethyl ether (mPEG-Ad) was further encapsulated into it to gain supramolecular micelles of mPEG-Ad@BAC-CDen. Then mPEG-Ad@BAC-CDen/CPT supramolecular micelles could be easily obtained by incorporation of CPT into mPEG-Ad@BAC-CDen via dialysis method. The particle size of supramolecular micelles increased from 106 nm (bare micelles) to 142 nm (CPT loaded micelles), suggesting their passive targeting potential to tumor tissue. Owing to the reduction degradability of disulfide linker in main chain of BAC-CDen, the CPT could be sustainably released from the above micelles with the gradual cleavage of polymer in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition. It was noted that the stability of CPT in aqueous media was remarkably improved in the mPEG-Ad@BAC-CDen supramolecular micelles, which effectively protected the active lactone ring of CPT from hydrolysis under physiological condition. Besides, compared with free CPT, the CPT-loaded supramolecular micelles showed much lower cytotoxicity against L929 cell line. All these results suggested the potential utilization of the mPEG-Ad@BAC-CDen supramolecular micelles as the carriers of hydrophobic drugs with better stability and lower cytotoxicity. And the resulted anti-tumor CPT supramolecular micelles can be delivered to tumor cells with a high selectivity.
研究领域:
药剂学
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肿瘤学
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生物化学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2026
·
IF 6.2
Qiang Wang,Wenqian Qian,Boxu Liang,Xianghuang Mei,yuchao lu,Wei Guo,Xiao Duan
Camptothecin (CPT) is a highly potent antitumor agent with severe systemic toxicity in clinical application. To employ the endogenous molecule of oxidized glutathione (GSSG) as carrier for CPT delivery could simultaneously avoid the carrier’s accumulative toxicity and drug’s systemic toxicity. The poly-GSSG was conjugated with CPT to develop a glutathione-responsive nanomedicine (Poly GSSG-CPT). The structure of poly GSSG-CPT was confirmed through FT-IR, NMR, and MALDI-TOF analyses. The cumulative CPT release rate from Poly GSSG-CPT reached 97.9% at 120 h in a 10 mg·mL-1 glutathione (GSH) environment measured by UV-Vis spectroscopy. CCK-8 assays and flow cytometry experiments exhibited similar cell inhibitory effects between Poly GSSG-CPT and CPT. Furthermore, laser scanning confocal microscopy (CLSM) and in vivo imaging (IVIS) showed that Poly GSSG-CPT could localize to cell nuclei within 6 h and accumulate in tumor tissue within 48 h. Tumor-bearing mice studies and histopathological analyses confirmed that Poly GSSG-CPT could significantly enhance antitumor efficacy and reduce systemic toxicity compared to free CPT. Altogether, the nanomedicine of Poly GSSG-CPT based on GSSG and CPT showed the superior stability in aqueous environment, higher tumor inhibition ability and lower side effects in vivo, demonstrating that the endogenous molecule as carriers is a better choice for developing nanomedicine with higher therapeutic efficacy and lower systemic toxicity
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yadong Liu,Yifan Xue,Junjie Tang,Peng Zhang,Changjiang Liu,Dalin Wu,Jie Liu
Porphyrin-based photosensitizers are extensively utilized in the realm of photodynamic therapy, capitalizing on their advantageous optical, chemical, and electronic properties. Nonetheless, their application is often constrained by their pronounced hydrophobicity. Structures with a high load capacity and excellent biocompatibility are preferred options to circumvent this obstacle. Herein, we constructed a novel porphyrin–camptothecin (CPT) polymer, which is composed of amphiphilic oxazoline segments, and the drug monomers containing disulfide bonds are modified on the hydrophobic chain of polyoxazoline. The polyoxazoline–porphyrin–CPT (OPC) polymer can self-assemble into nanoparticles in the aqueous phase, possesses excellent stability, and generates abundant singlet oxygen (1O2) under laser irradiation. Additionally, the OPC nanoparticles exhibit satisfactory biocompatibility and high light toxicity against 4T1 cells. In the microenvironment of the tumor, drugs were released from the OPC nanoparticles owing to the high concentration of GSH, causing direct damage to the tumor cell, achieving the combination of photo-chemotherapy. The findings of this research indicate that polyoxazoline porphyrin demonstrates adaptability as a nanoplatform for cancer treatment.
研究领域:
药学
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纳米技术
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生物医学工程
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xikuang Yao,Changrui Sun,Fei Xiong,Weina Zhang,Wenjing Yao,Yinghui Xu,Wenpei Fan,Fengwei Huo
Nanomedicine-enhanced immunogenic cell death (ICD) has attracted considerable attention for its great potential in cancer treatment. Even though polyethylene glycol (PEG) is widely recognized as the gold standard for surface modification of nanomedicines, some shortcomings associated with this PEGylation, such as hindered cell endocytosis and accelerated blood clearance phenomenon, have been revealed in recent years. Notably, polysarcosine (PSar) as a highly biocompatible polymer can be finely synthesized by mild ring-opening polymerization (ROP) of sarcosine N-carboxyanhydrides (Sar-NCAs) and exhibit great potential as an alternative to PEG. In this article, PSar-b-polycamptothecin block copolymers are synthesized by sequential ROP of camptothecin-based NCAs (CPT-NCAs) and Sar-NCAs. Then, the detailed and systematic comparison between PEGylation and PSarylation against the 4T1 tumor model indicates that PSar decoration can facilitate the cell endocytosis, greatly enhancing the ICD effects and antitumor efficacy. Therefore, it is believed that this well-developed PSarylation technique will achieve effective and precise cancer treatment in the near future.
研究领域:
肿瘤学
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药剂学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ASIA-PACIFIC ENTOMOLOGY
·
2024
·
IF 1.1
Jun-li Lv,Wen-qing Lai,Lei Pang,Xiao-ying Zhang,Kai-yi Zheng,Qiang Zhang,Zhan-peng Lu,Zhi-sheng Wang,Fasihul Lisan,Xue-yang Wang,Lu-feng Hu,Ming-jie Deng
Camptothecin (CPT) is derived from Camptotheca acuminate and its main action is the inhibition of the DNA topoisomerase I (Top I) complex. Therefore, CPT and its derivatives are always used as antitumor and antimicrobial agents and also have some insecticidal effects. However, the mode of action underlying the toxicity of CPT to the virulence of pests is still not fully understood. In this study, the effects of CPT on Spodoptera frugiperda ( S. frugiperda ) were determined by performing toxicity assessments, metabolomics, and mechanism analysis. The results showed that CPT increased the efficiency of inhibition of larval weight in a dose and time-dependent manner. In addition, the metabolomics of 5th-instar larval hemolymph was determined by UPLC-MS/MS and 1 H NMR analysis. UPLC-MS/MS analysis showed that the energy metabolic pathway was more important than the amino acid pathway for the resistance of S. frugiperda to CPT. Furthermore, metabolites involved in the energy metabolic pathway were analyzed using 1 H NMR, and fumarate and pyruvate were identified as interesting metabolites. Bioassays confirmed that they play a key role in enhancing the resistance of S. frugiperda larvae to CPT. Finally, the underlying mechanisms were found to be related to the restorative effects of the two metabolites on metabolic pathways associated with the TCA cycle. In a word, CPT is a potential biological insecticide that exhibits a strong toxicological effect against S. frugiperda by inhibiting the TCA cycle, which provides theoretical support for applying CPT in the control of pests.
研究领域:
昆虫学
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药理学
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代谢组学
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毒理学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）