JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2026
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IF 5.2
Li-jun Yang,Shuang Zhao,Sheng-xia Hu,Xin-yue Li,Xiao-hui Zhang,Le-han Wang,Ling Tang
Ovarian cancer (OC) remains highly lethal, primarily due to late-stage diagnosis, peritoneal metastasis, high recurrence rates, and a tumor microenvironment (TME) that suppresses immune responses, limiting treatment efficacy. To address these challenges, this study developed a novel targeted nanoplatform, PPT/FSHB-PNP-SA, to target intraperitoneal OC cells and inhibit there growth. The system utilizes an amphiphilic polymer (PNP-SA) formed by the covalent coupling of bioactive ginseng polysaccharide (PNP) with stearic acid (SA). PNP-SA self-assemble into microspheres, encapsulating the podophyllotoxin (PPT), and is modified with DSPE-PEG 2000 -FSHB on its surface. DSPE-PEG 2000 -FSHB enables the micelles to specifically target OC cells expressing the follicle-stimulating hormone receptor (FSHR). The PPT/FSHB-PNP-SA system exhibits dual anti-tumor effects: (1) PPT directly induces cancer cell apoptosis; (2) The PNP shell actively remodels the immunosuppressive TME by inhibiting immunosuppressive pathways and promoting M1 macrophage polarization. This combined chemotherapy-immunotherapy strategy, which integrates targeted delivery with TME remodeling, offers a promising treatment option for recurrent/resistant OC.
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Chemical Biology & Drug Design
·
2022
·Vol. 99
·期 6
·828-838
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IF 2.873
Yan Zhao,Danyao Li,Yun Han,Haohao Wang,Rui Du,Zhaowei Yan
Infantile hemangioma (IH) is a common benign endothelial cell tumor in infants and young children, sometimes accompanied by potential complications, and may develop into malignant tumors. Hemangioma endothelial cells (HemECs) are one of the main components of IH. Podophyllotoxin (PPT) has been reported to have many pharmacological activities, especially anti-tumor, but its high toxicity, poor water solubility, and serious gastrointestinal side effects limit its clinical application. In this study, we have designed and synthesized 20 ester derivatives by introducing Boc-amino acids or organic acids at the C-4 position of podophyllotoxin through esterification reactions. The cytotoxicity of these compounds was evaluated on HemECs. Changes in cell proliferation and apoptotic signaling pathways were studied by DAPI staining, colony formation assay, migration assay, measurement of reactive oxygen species (ROS) levels flow cytometry, and Western blot analysis. We found that eight of the compounds were more potent than PPT. Of these, compound V-31 was the most active (IC 50 = 0.079 ± 0.0049 µM). Further research indicated that compound V-31 inhibited its proliferation and migration, increased the level of ROS in cells, and induced apoptosis by downregulating p-PI3K, p-Akt, and Bcl-2, and upregulating cleaved caspase-3 and Bax. Our research provides the first insight into the application of PPT derivatives in HemECs, may provide an effective medicine for IH treatment.
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Pharmaceutics
·
2022
·Vol. 14
·期 9
·1765
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IF 6.525
Bo Yu,Yiping Shen,Xuejie Zhang,Lijuan Ding,Zheng Meng,Xiaotong Wang,Meihua Han,Yifei Guo,Xiangtao Wang
Owing to its pH-sensitive property and chelating Cu2+effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC50value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application.Keywords:poly(methacrylate citric acid);doxorubicin;pH sensitive;chelating Cu2+effect
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Journal of Inflammation Research
·
2022
·
IF 4.631
Huixia Feng,Guilin Chen,Yongli Zhang,Mingquan Guo
Background Dysosma versipellis ( D. versipellis ) has been traditionally used as a folk medicine for ages. However, the specific phytochemicals responsible for their correlated anti-inflammatory, anti-proliferative and antiviral activities remain unknown. Purpose This study aimed to explore the specific active components in D. versipellis responsible for its potential anti-inflammatory, anti-proliferative, and antiviral effects, and further elucidate the corresponding mechanisms of action. Methods Bioaffinity ultrafiltration coupled to liquid chromatography–mass spectrometry (UF-LC/MS) was firstly hired to fast screen for the anti-inflammatory, anti-proliferative and antiviral compounds from rhizomes of D. versipellis , and then further validation was conducted using in vitro inhibition assays and molecular docking. Results A total of 12, 12, 9 and 12 phytochemicals with considerable affinities to Topo I, Topo II, COX-2 and ACE2 were fished out, respectively. The anti-proliferative assay in vitro indicated that podophyllotoxin and quercetin exhibited comparably strong inhibitory rates on A549 and HT-29 cells compared with 5-FU and etoposide. Meanwhile, kaempferol displayed prominent dose-dependent inhibition against COX-2 with IC 50 value at 0.36 ± 0.02 μM lower than indomethacin at 0.73 ± 0.07 μM. Furthermore, quercetin exerted stronger inhibitory effect against ACE2 with IC 50 value at 104.79 ± 8.26 μM comparable to quercetin 3- O -glucoside at 135.25 ± 6.54 μM. Conclusion We firstly showcased an experimental investigation on the correlations between bioactive phytochemicals of D. versipellis and their multiple drug targets reflecting its potential pharmacological activities, and further constructed a multi-target and multi-component network to decipher its empirical traditional applications. It could not only offer a reliable and valuable experimental basis to better comprehend the curative effects of D. versipellis but also provide more new insights and strategies for other traditional medicinal plants.
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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.
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Feng Huixia,Chen Guilin,Zhang Yongli,Guo Mingquan
Podophyllum sinense (P. sinense) has been used as a traditional herbal medicine for ages due to its extensive pharmaceutical activities, including antiproliferative, anti-inflammatory, antiviral, insecticidal effects, etc. Nevertheless, the specific bioactive constituents responsible for its antiproliferative, anti-inflammatory, and antiviral activities remain elusive, owing to its complicated and diversified chemical components. In order to explore these specific bioactive components and their potential interaction targets, affinity ultrafiltration with multiple drug targets coupled with high performance liquid chromatography/mass spectrometry (UF–HPLC/MS) strategy was developed to rapidly screen out and identify bioactive compounds against four well-known drug targets that are correlated to the application of P. sinense as a traditional medicine, namely, Topo I, Topo II, COX-2, and ACE2. As a result, 7, 10, 6, and 7 phytochemicals were screened out as the potential Topo I, Topo II, COX-2, and ACE2 ligands, respectively. Further confirmation of these potential bioactive components with antiproliferative and COX-2 inhibitory assays in vitro was also implemented. Herein, diphyllin and podophyllotoxin with higher EF values demonstrated higher inhibitory rates against A549 and HT-29 cells as compared with those of 5-FU and etoposide. The IC50 values of diphyllin were calculated at 6.46 ± 1.79 and 30.73 ± 0.56 μM on A549 and HT-29 cells, respectively. Moreover, diphyllin exhibited good COX-2 inhibitory activity with the IC50 value at 1.29 ± 0.14 μM, whereas indomethacin was 1.22 ± 0.08 μM. In addition, those representative constituents with good affinity on Topo I, Topo II, COX-2, or ACE2, such as diphyllin, podophyllotoxin, and diphyllin O-glucoside, were further validated with molecular docking analysis. Above all, the integrated method of UF–HPLC/MS with multiple drug targets rapidly singled out multi-target bioactive components and partly elucidated their action mechanisms regarding its multiple pharmacological effects from P. sinense, which could provide valuable information about its further development for the new multi-target drug discovery from natural medicines.
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NATURAL PRODUCT RESEARCH
·
2021
·
IF 2.862
Meitao Duan,Ahmed Mahal,Ban Mohammed,Yongyan Zhu,Huaming Tao,Shaoyu Mai,Maysoon Al-Haideri,Quanhong Zhu
Three new derivatives of tetrahydrocurcumin 6, 7 and 9 have been prepared as potent antitumor agents using copper(II)-catalyzed ‘click chemistry’. Their structures were identified using 1H-NMR, 13C-NMR and HRMS techniques. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay has been carried out to investigate the in vitro cytotoxicity against human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2) and human colon carcinoma (HCT-116). Compound 6 has showed significant inhibitory activity against HCT-116 cell line with an IC50 value of 17.86 μM compared to tetrahydrocurcumin (50.96 μM) and positive control etoposide (19.48 μM) while showed no inhibitory activity against NCM460 cell line. Compounds 7 showed moderate inhibitory activity compared to tetrahydrocurcumin and etoposide while compound 9 showed no obvious inhibitory activity. The results suggested further structure modifications of tetrahydrocurcumin to improve its anticancer activity.
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CHINESE JOURNAL OF CHEMISTRY
·
2020
·Vol. 38
·期 7
·690-696
·
IF 3.826
Jiali Sun,Qi Wei,Na Shen,Zhaohui Tang,Xuesi Chen
Summary of main observation and conclusion Physical encapsulation of drugs into polymer micelles is a common method of loading hydrophobic drugs. Methoxy polyethylene glycol-poly( D , L -lactide) (mPEG-PDLLA) is one of the most commonly used drug carrier. At present, whether a carrier is suitable for the loading of a certain drug is determined by drug loading experiments. This process costs a lot of time. Therefore, an efficient predicting method to avoid time-consuming tests is critical. In this study, we prepared mPEG 5k -PDLLA 5k and used it to load a series of drugs. Three parameters were used to test the miscibility of mPEG 5k -PDLLA 5k with drugs, including absolute difference in Hildebrand solubility parameters (|Δ δ |), Flory–Huggins interaction parameter ( χ ) and the distance ( D value) calculated from the two-dimensional solubility parameters. We found the two-dimensional solubility parameters obtained from JB2013 group contribution (GC) method was useful. By comparing the drug loading content (DLC) with the D value, we found that when the D value was less than 5.0 (MJ/m 3 ) 1/2 , the miscibility of drug and mPEG 5k -PDLLA 5k was good and drug loading capability was high; when the D value was more than 8.0 (MJ/m 3 ) 1/2 , the drug was barely loaded. Thus, this work provided a rationale to qualitatively predict the loading capability of mPEG 5k -PDLLA 5k for hydrophobic drugs.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Mei Dong,Cheng Zhao,Yongfang Huang,Ke Zheng,Guanhu Bao,Fenglin Hu,Fan Peng,Mingjun Chen,Zengzhi Li,Ruili Lu
ABSTRACT Cordyceps chanhua on artificial media has been approved as a medicine food homology product. However, the metabolites have not been extensively studied. HPLC-HRMS analysis showed that there were 11 main metabolites in the EtOAc extract including 4 probable unknown compounds. Fumosoroseain A with anti-aging effects is the most abundant known compound and was identified from C. chanhua for the first time. The second abundant compound is N 6 -(2-Hydroxyethyl) adenosine, a typical metabolite of C. chanhua . All the known compounds have consistent health function with that of the fungus. HRMS, 1D and 2D NMR analyses revealed that compounds 2 , 3, and 4 are new nucleosides named as chanhuanosides A, B, and C. Compound 1 is the known compound cordyrrole B isolated from C. chanhua for the first time whose structure is firstly confirmed by single crystal X-ray analysis. Bioactivity analysis revealed that 1 - 4 significantly inhibited pancreatic lipase acitivty, and strongly promoted the proliferation of RAW264.7 and 293 T cells, suggesting that they might have ant-obesity, immunoregulation, and renal protection functions. Structure-bioactivity analysis revealed that the esterification on ribose can increase their bioactivity. Present metabolites study suggests that C. chanhua cultured on the artificial medium is a promising health food.
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JOURNAL OF CHROMATOGRAPHY A
·
2023
·
IF 4.1
Lidong Cheng,Zhiqing Mo,Qiongzhi Zhang,Man Yang,Xianglin Liao,Liyu Qiu,Shizhong Wang,Xixiang Yang,Xiaogang Hu
A novel hydroxylpropyl cellulose (HPC) modified graphene oxide (GO)-based molecularly imprinted polymers (HPC-GO-MIP) have been developed as a solid phase extraction (SPE) material for the selective separation and extraction of podophyllotoxin. In this strategy, the cellulose with rich hydroxyl groups was introduced to form bi-functional monomers with methacrylic acid to provide more recognition sites for the improving of extraction efficiency, then GO was added as a two-dimensional substrate for MIP to improve the material morphology and surface area. The extraction performances of obtained HPC-GO-MIP material were tested, and the results prove its high efficiency and selectivity for podophyllotoxin extraction. The saturated adsorption capacity reached 23.1 μg/mg, and high enrichment efiiciency of 463.8 folds was realized under the premise of ensuring the recovery rate. The selective imprinting factor was much higher than those of kaempferol and quercetin, which were the main compounds in podophyllum fruit. Under the optimized SPE conditions, the HPC-GO-MIP based SPE-HPLC method showed the detection limit of 14.2 ng/mL for podophyllotoxin assay. When applied to podophyllum fruit samples, the material showed excellent ability of selective separation and enrichment of podophyllotoxin, and the relative standard deviations (RSD) of intra and inter batches were less than 8.1 % and 5.7 % in real samples detection. The HPC-GO-MIP SPE method broadened the application for high multiple extraction in trace analyte samples and provided a valuable solution to improve the selective separation and detection.
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Oncologie
·
2023
·Vol. 25
·期 3
·233-243
·
IF 0.9
Simin Deng,Yuan Xu,Binbin Gao,Tingting Yu,Lun Kuang,Bo’ang Han,Shaolun Feng,Haodong Chi,Qing Cao,Shen Yue,Chen Liu
Objectives
The Sonic hedgehog (SHH) signaling is essential in animal development and tissue homeostasis. Aberrant activation of SHH pathway has been implicated in tumorigenesis and progression of several cancers, including ovarian cancer. Therefore, targeting SHH pathway may pave the way for successful ovarian cancer treatment.
Methods
To identify the potential SHH inhibitors from traditional Chinese medicines, we herein employed two in vitro cell models. In addition, western blotting and quantitative real-time PCR were performed to evaluate the inhibitory activity of Anemarrhenasaponin I (An-I) on SHH signaling in ovarian cancer cells. Cell proliferation assay and transwell assay were used to assess the effect of An-I on tumorigenicity. We also applied RNA-seq to examine the potential mechanism of An-I against ovarian cancer.
Results
Drug screening results showed that An-I drastically inhibited SHH signaling. More importantly, An-I effectively suppressed ovarian cancer cell proliferation and aggressiveness. RNA-seq-based transcriptome data showed that An-I affected ovarian cancer cells by suppressing SHH-WNT-Matrix metalloproteinases (MMPs) pathway.
Conclusions
An-I suppressed ovarian cancer progression by inhibiting SHH-WNT-MMP signaling transduction, providing a new treatment strategy for ovarian cancer.
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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.
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危险品化学品经营许可证（带存储）