INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2016
·
IF 3.138
Chao Chen,Yong Yu,Xiaoli Wang,Ping Shi,Yibing Wang,Ping Wang
Podophyllotoxin (PPT) offers a broad-spectrum of anticancer activities, but little has been reported for its controlled release. This work shows that by manipulating molecular interactions between PPT and Chitosan, efficient nanoscale capsulation of PPT can be realized. The drug encapsulation efficiency is as high as 52%, with a final particle drug loading in the order of 10% (wt/wt). It further demonstrates that changes in pH can also significantly affect the rate of drug release from the Chitosan nanoparticles. Upon contact with cancer cells, chitosan nanoparticles enable efficient internalization and drug release. In vitro evaluations with HepG-2 and MCF-7 cells indicate that the chitosan nanoparticle carriers can improve drug efficacy in comparison to free PPT, most likely by regulating the intrinsic apoptotic signaling pathway to induce apoptosis. Overall, PPT chitosan nanoparticles promise a safe and efficient drug delivery system for PPT.
研究领域:
药理学
·
生物材料
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Bingfeng Liang,Dangxia Zhou
Although podophyllotoxin (POD) demonstrates high efficiency to inhibit various cancers, its clinic application is limited to poor bioavailability. Nanoparticles derived from homodimeric prodrugs with high drug loading potential are emerging as promising nanomedicines. However, complete intracellular drug release remains a major hindrance to the use of homodimeric prodrugs-based nanomedicine. We sought to develop a reactive oxygen species (ROS) responsive POD dimeric prodrug by incorporating vitamin K3 (VK3) and Pluronic F127 to synthesize a spheroid nanoparticle (PTV-NPs). PTV-NPs with high POD content could release drugs under the ROS enrichment microenvironment in cancer cells. The released VK3 could produce abundant ROS selectively in tumor cells catalyzed by the overexpressed NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme. In turn, the resultant high ROS concentration promoted the conversion of POD dimeric prodrug to POD monomer, thereby achieving the selective killing of cancer cells with weak system toxicity. In vitro and in vivo studies consistently confirmed that PTV-NPs exhibit high drug loading potential and upstanding bioavailability. They are also effectively internalized by tumor cells, induce abundant intracellular ROS generation, and have high tumor-specific cytotoxicity. This ROS-responsive dimeric prodrug nanoplatform characterized by selective self-amplification drug release may hold promise in the field of antitumor drug delivery.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2017
·
IF 3.181
Ruige Yang,Xiaobo Huang,Zhiping Che,Yuanyuan Zhang,Hui Xu
Podophyllotoxin is isolated as a sustainable natural bioresource from the roots and rhizomes of Podophyllum hexandrum and Juniperus Sabina . In continuation of our program aimed at the discovery of biorenewable natural product-based pesticides, a series of 4α-acyloxy derivatives of 2'-chloro-5-bromopicropodophyllotoxin or 2',5-dibromopicropodophyllotoxin were synthesized by structural modification of podophyllotoxin, and evaluated as insecticidal and acaricidal agents against two serious agricultural pests, Mythimna separata Walker and Tetranychus cinnabarinus Boisduval. Among all derivatives, compounds 6a and 7a exhibited more promising insecticidal and acaricidal activities than podophyllotoxin, and the final mortality rates of 6a , 7a and 1 against M. separata (at 1 mg/mL) and T. cinnabarinus (at 0.5 mg/mL) were 50%/53.3%/36.7%, and 33%/41.8%/1.6%, respectively. This suggested that introduction of the acetoxy moiety at the C-4 position of 2'-chloro-5-bromopicropodophyllotoxin/2',5-dibromopicropodophyllotoxin was necessary for the insecticidal and acaricidal activities.
研究领域:
植物化学
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害虫管理
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农业科学
✓ 已验证
产品关联
DOI
高影响因子
Natural Product Communications
·
2019
·
IF 0.554
Cheng-Ting Zi,Liu Yang,Bang-Lei Zhang,Yan Li,Zhong-Tao Ding,Zi-Hua Jiang,Jiang-Miao Hu,Jun Zhou
Novel podophyllotoxin xyloside derivatives 8 to 11 were synthesized and evaluated for their cytotoxicities against a panel of 5 human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using [3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. These derivatives showed good to moderate activities, with compound 9 having an IC50 value of 4.42 μM against the A-549 cell line. Overall, compound 9 might be a promising candidate for further development.
研究领域:
药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2014
·Vol. 16
·期 8
·1-11
·
IF 2.278
Zhu Shaojia,Zhen Hong,Li Yongjun,Wang Ping,Huang Xiaoyu,Shi Ping
Graphene, a two-dimensional nanomaterial, has become a hot spot of research at the interface of nanotechnology and biomedicine. In this study, the oxidized form of graphene, graphene oxide (GO), was functionalized with 6-armed polyethylene glycol (PEG), which rendered it stable and biocompatible in physiological solution. The successful synthesis of PEGylated graphene oxide (GO-PEG) nanocarrier with low toxicity was confirmed by UV–Vis spectroscopy, Fourier-transform infrared spectroscopy, atomic force microscopy, and thermogravimetric analysis. By dynamic light scattering (DLS), the size distribution of the nanoparticles were shown to be 60–200 nm. Furthermore, a complex by loading an aromatic anticancer compound, podophyllotoxin (PPT), onto GO-PEG (GO-PEG/PPT) via π – π stacking and hydrophobic interactions was investigated. It was demonstrated that GO-PEG/PPT showed remarkably high cytotoxicity compared to free PPT in both the human cervical adenocarcinoma HeLa cell line and human hepatoma SMMC-7721 cell line. The loading and delivery of anticancer drugs using this kind of graphene-based nanocarrier may find potential application in biomedicine.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Yajing Liu,Shaojia Zhu,Kaizhi Gu,Zhiqian Guo,Xiaoyu Huang,Mingwei Wang,Hesham M. Amin,Weihong Zhu,Ping Shi
Theranostic prodrug therapy enables the targeted delivery of anticancer drugs with minimized adverse effects and real-time in situ monitoring of activation of the prodrugs. In this work, we report the synthesis and biological assessment of the near-infrared (NIR) prodrug DCM-S-PPT and its amphiphilic copolymer (mPEG-DSPE)-encapsulated nanoparticles. DCM-S-PPT is composed of podophyllotoxin (PPT) as the anticancer moiety and a dicyanomethylene-4H-pyran (DCM) derivative as the NIR fluorescent reporter, which are linked by a thiol-specific cleavable disulfide bond. In vitro experiments indicated that DCM-S-PPT has low cytotoxicity and that glutathione (GSH) can activate DCM-S-PPT resulting in PPT release and a concomitant significant enhancement in NIR fluorescence at 665 nm. After being intravenously injected into tumor-bearing nude mice, DCM-S-PPT exhibited excellent tumor-activated performance. Furthermore, we have demonstrated that mPEG-DSPE as a nanocarrier loaded with DCM-S-PPT (mPEG-DSPE/DCM-S-PPT) showed even greater tumor-targeting performance than DCM-S-PPT on account of the enhanced permeability and retention effect. Its tumor-targeting ability and specific drug release in tumors make DCM-S-PPT a promising prodrug that could provide a significant strategy for theranostic drug delivery systems.
研究领域:
药学
·
生物医学工程
·
癌症研究
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纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2019
·
IF 3.208
Cheng-Ting Zi,Liu Yang,Qing-Hua Kong,Hong-Mei Li,Xing-Zhi Yang,Zhong-Tao Ding,Zi-Hua Jiang,Jiang-Miao Hu,Jun Zhou
Background Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4β-triazolyl-podophyllotoxin glycosides show good anticancer activity, the per-acetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied.Methods A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure–activity relationship and the physicochemical property–anticancer activity relationship of these compounds.Results Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27±0.21 to 11.37±0.52 μM. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA < 20, ClogP > 2, MW > 700 Da, and RB > 10.Conclusion We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.
研究领域:
药理学
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肿瘤学
·
有机化学
✓ 已验证
DOI
高影响因子
PLoS One
·
2013
·Vol. 8
·期 8
·e72099
·
IF 3.73
Juan Li,Hua Sun,Lu Jin,Wei Cao,Jin Zhang,Chong-Yi Guo,Ke Ding,Cheng Luo,Wen-Cai Ye,Ren-Wang Jiang
Podophyllotoxin (POD) is a lignan-type toxin existing in many herbs used in folk medicine. Until now, no effective strategy is available for the management of POD intoxication. This study aims to determine the protective effects of flavonoids (quercetin and kaempferol) on POD-induced toxicity. In Vero cells, both flavonoids protected POD-induced cytotoxicity by recovering alleviating G2/M arrest, decreasing ROS generation and changes of membrane potential, and recovering microtubule structure. In Swiss mice, the group given both POD and flavonoids group had significantly lower mortality rate and showed less damages in the liver and kidney than the group given POD alone. As compared to the POD group, the POD plus flavonoids group exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde levels, and increases in superoxide dismutase and glutathione levels. Histological examination of the liver and kidney showed less pathological changes in the treatment of POD plus flavonoids group. The protective mechanisms were due to the antioxidant activity of flavonoids against the oxidative stress induced by POD and the competitive binding of flavonoids against POD for the same colchicines-binding sites. The latter binding was confirmed by the tubulin assembly assay in combination with molecular docking analyses. In conclusion, this study for the first time demonstrated that the coexisting flavonoids have great protective effects against the POD toxicity, and results of this study highlighted the great potential of searching for effective antidotes against toxins based on the pharmacological clues.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 3
·784
·
IF 5.4
Xinhui Wang,Yuequan Wang,Jiaxin Yu,Qian Qiu,Rui Liao,Shenwu Zhang,Cong Luo
Podophyllotoxin (PPT) has shown strong antitumor effects on various types of cancers. However, the non-specific toxicity and poor solubility severely limits its clinical transformation. In order to overcome the adverse properties of PPT and explore its clinical potential, three novel PTT−fluorene methanol prodrugs linked by different lengths of disulfide bonds were designed and synthesized. Interestingly, the lengths of the disulfide bond affected the drug release, cytotoxicity, pharmacokinetic characteristics, in vivo biodistribution and antitumor efficacy of prodrug NPs. To be more specific, all three PPT prodrugs could self-assemble into uniform nanoparticles (NPs) with high drug loading (>40%) via the one-step nano precipitation method, which not only avoids the use of surfactants and cosurfactants, but also reduces the systemic toxicity of PPT and increases the tolerated dose. Among the three prodrug NPs, FAP NPs containing α-disulfide bond showed the most sensitive tumor-specific response and fastest drug release rate, thus demonstrating the strongest in vitro cytotoxicity. In addition, three prodrug NPs showed prolonged blood circulation and higher tumor accumulation. Finally, FAP NPs demonstrated the strongest in vivo antitumor activity. Our work will advance the pace of podophyllotoxin towards clinical cancer treatment.Keywords:podophyllotoxin;chemotherapy;prodrug;tumor-specific response;nanodrug delivery system
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2025
·
IF 4.3
Jiangxiu Niu,Ming Yuan,Liye Wang,Pei Zhang,Xingang Cui,Yanli fan,Xianghui Liu,Jucai Wang
Podophyllotoxin (POD) serves as the primary therapeutic agent for the external management of genital warts. However, traditional POD tinctures often cause severe systemic adverse reactions, due to the drug being absorbed through the skin into the bloodstream. Therefore, it is particularly important to develop new topical preparations for POD to enhance topical administration and reduce systemic absorption. Herein, POD-loaded keratin-functionalized transfersomes (POD-KTFs) were developed and characterized, and the skin permeation and deposition, the intradermal fluorescence distribution, and the influence of POD-KTFs on a skin structure were evaluated. The hydrodynamic diameter and surface potential of POD-KTFs were 183.1 nm and −33.9 mV, respectively. The image of scanning electron microscopy (SEM) indicated that the POD-KTFs had a spherical appearance. The X-ray diffraction (XRD) pattern confirmed that POD mainly existed in its amorphous form in POD-KTFs. Meaningfully, POD-KTFs increased the deposition of POD in porcine ear skin by 2.14 and 1.80 times, respectively, compared to the POD tincture and POD-loaded transfersomes (POD-TFs), while the transdermal penetration of POD in POD-KTFs was obviously less than that of POD tincture (p < 0.001) and POD-TFs (p < 0.01). Using coumarin-6 as a fluorescent probe, fluorescence imaging of skin sections revealed that the POD-KTFs were mainly distributed in the epidermis. In addition, POD-TFs could promote the drug to pass through the stratum corneum (SC) by affecting the structure of the SC on the skin surface. Therefore, this study might provide an efficient way to improve the topical delivery of POD to the epidermis of the skin, thereby enhancing the therapeutic effect of genital warts.
研究领域:
药剂学
·
皮肤科
·
纳米技术
·
药物递送
·
生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2017
·Vol. 13
·期 11
·1435-1445
·
IF 4.521
Wang Tingting,Song Yonghong,Zhang Wencheng,Wu Zeyu,Li Fei,Su Yang,Yang Yi,Li Fangyuan,Chen Pengpeng,Wang Jing,Wu Qiang,Sun Xiaolian,Lu Yang,Ling Daishun
As a phenyltetralin-type lignin isolated from roots and rhizomes of Podophyllum hexandrum, podophyllotoxin (POD) possesses a great deal of biological activities, especially the anticancer activity via preventing the division of cancerous cells. However, its practical clinical
application as an anticancer agent is hindered by its poor water solubility and serious side effects. Herein, we enclosed the POD into the hydrophobic cavity of natural phosphatidylcholine based liposomes to improve its solubility and thus, enhance the chemotherapeutic effect. Modified gold
nanorods (GNRs) were further conjugated onto the liposomal POD composite (GLP) for enhanced photothermal stability. The extinction coefficient of GLP aqueous dispersion at 808 nm was calculated to be 8.08 Lg–1 cm–1, and the photothermal conversion efficiency
was calculated to be 46.1%. In addition, the release of POD from GLP composite was effectively triggered by NIR irradiation. Compared with the cellular viabilities in the single chemotherapy group (54.6%) and the single photothermal therapy group (66.9%), only 10.3% 4T1 cells were survived
after photothermal and chemotherapy simultaneously in the GLP group after exposure to 808 nm NIR laser at an intensity of 1.0 W/cm2 for 5 min. The cytotoxicity and hemolysis assay further demonstrated the excellent biocompatibility of POD based liposomal composite. Overall, the
GNRs conjugated liposomal POD is a promising therapeutic nanoagent for synergistic chemo-thermal therapy.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2018
·Vol. 17
·期 5
·6506-6514
·
IF 1.922
Yan Gao,Kai Han,Qi Wang,Zhili Hu,Qingxiu Liu,Lishi Liu,Kang Zeng
Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV). Podophyllotoxin (POD), a cytotoxic compound, is able to effectively treat HPV; however, the severe irritation side effects of POD restrict its use as a treatment for CA. The aim of the present study was to construct novel POD‑loaded nanostructured nanolipid carriers (POD‑NLCs) and evaluate their physicochemical characteristics and cytotoxicity. POD‑NLCs (0.5%) were prepared using emulsion‑evaporation and low temperature‑solidification methods with optimized conditions and preparations. Subsequently, the POD‑NLCs were physicochemically characterized and their in vitro and in vivo release efficiencies and in vitro cytotoxicity were studied. The prepared POD‑NLCs had an average particle size, ζ potential, polydispersity index and encapsulation efficacy of 178.5±20 nm, ‑27±0.5 mV, 0.18±0.01 and 82.9±2%, respectively. In vitro and in vivo release studies demonstrated that POD‑NLCs are able to provide sustained drug delivery for 72 h in vitro and 10 h in the mucosa. Compared with a tincture formulation of POD (POD‑T), POD‑NLC induced less inflammatory cytokine production in the cervical mucous and led to a decreased histopathological score. In addition, a cytotoxicity assay demonstrated that inhibition of the POD‑NLCs was 98.4% at 24 h and remained >98% up to 72 h. Furthermore, more cells were arrested in the G2/M phase of the cell cycle following POD‑NLC treatment compared with the POD‑T treatment. The present study provides evidence that POD‑NLC is a promising delivery system for the treatment of CA.
研究领域:
药学
·
药物递送系统
·
病毒学
·
性传播疾病
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）