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  • 1
    Online Resource
    Online Resource
    Sensitive Tumor Cell Line for Annonaceous Acetogenins and High Therapeutic Efficacy at a Low Dose for Choriocarcinoma Therapy
    American Scientific Publishers ; 2021
    In:  Journal of Biomedical Nanotechnology Vol. 17, No. 10 ( 2021-10-01), p. 2062-2070
    Details
    In: Journal of Biomedical Nanotechnology, American Scientific Publishers, Vol. 17, No. 10 ( 2021-10-01), p. 2062-2070
    Abstract: Annonaceous acetogenins (ACGs) have attracted much attention because of excellent antitumor activity. However, the lack of selectivity and the accompanying serious toxicity have eventually prevented ACGs from entering clinical application. To decrease the side effects of ACGs, the cytotoxicity of ACGs on 10 types of tumor cell lines was investigated by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-te trazolium (MTS) test to identify one that was very sensitive to ACGs. Meanwhile, ACGs nanoparticles (ACGs-NPs) were prepared using poloxamer 188 (P188) as an excipient so as to solve the problem of poor solubility and the in vivo delivery of ACGs. ACG-NPs were 163.9±2.5 nm in diameter, negatively charged, and spherical with a high drug loading content (DLC) of 44.9±1.2%. MTS assays demonstrated that ACGs had strong cytotoxicity against JEG-3, HeLa, SiHa, MCF-7, A375, A2058, A875, U-118MG, LN- 229, and A431 cells, among which JEG-3 cell line was extremely sensitive to ACGs with a 50% inhibitory concentration (IC50) value of 0.26 ng/mL, a very encouraging discovery. ACGs-NPs demonstrated very good dose-dependent antitumor efficacy in a broad range of 45?1200 μg/kg on JEG-3 tumor-bearing mice. At a very low dose (1200 μg/kg), ACGs-NPs achieved a high tumor inhibition rate (TIR) of 77.6% through oral administration, displaying a significant advantage over paclitaxel (PTX) injections that are currently used as first-line anti-choriocarcinoma drugs. In the acute toxicity study, the half lethal dose (LD50) of ACGs-NPs was 135.5 mg/kg, which was over 100 times as of the effective antitumor dose, indicating good safety of ACGs-NPs. ACGs-NPs show promise as a new type of and potent anti-choriocarcinoma drug in the future.
    Type of Medium: Online Resource
    ISSN: 1550-7033
    URL: Article
    DOI: 10.1166/jbn.2021.3175
    Language: English
    Publisher: American Scientific Publishers
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Enhanced Solubility and Antitumor Activity of Annona Squamosa Seed Oil via Nanoparticles Stabilized with TPGS: Preparation and In Vitro and In Vivo Evaluation
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 6 ( 2022-06-10), p. 1232-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 6 ( 2022-06-10), p. 1232-
    Abstract: Annona squamosa seed oil (ASSO), which is a waste product in the extraction of annonaceous acetogenins (ACGs), displays good antitumor activity against a variety of tumor cells. However, ASSO is insoluble and has low bioavailability. In order to improve the solubility and application value of ASSO, the seed oil nanoparticles (ASSO-NPs) were successfully prepared only using TPGS as a stabilizer. ASSO-NPs obtained were spherical with a uniform size (less than 200 nm). ASSO-NPs showed the good storage stability at 25 ± 2 °C and were suitable for both oral administration and intravenous injection. The antitumor study in vitro and in vivo demonstrated more enhanced antitumor efficacy of ASSO-NPs than free ASSO. The ASSO-NPs group (15 mg/kg) had the highest tumor inhibition rate (TIR) of 69.8%, greater than the ASSO solution (52.7%, 135 mg/kg, p 〈 0.05) in 4T1 tumor-bearing mice. The in vivo biodistribution data displayed that the fluorescence intensity of ASSO/DiR-NPs in tumor was similar to that in liver in the presence of the reticuloendothelial system. Besides, the relative tumor-targeting index (RTTI) of (ACGs + ASSO)-NPs was 1.47-fold that of ACGs delivered alone, and there is great potential in ASSO-NPs as tumor-targeted delivery vehicles. In this study, ASSO-NPs were firstly prepared by a very simple method with fewer excipients, which improved the solubility and antitumor activity of the ASSO, displaying a good prospect in the in vivo delivery of natural bioactive compounds.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14061232
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 3
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    Online Resource
    Ginsenoside Rb1 stabilized and paclitaxel / protopanaxadiol co-loaded nanoparticles for synergistic treatment of breast tumor
    Elsevier BV ; 2023
    In:  Biomedicine & Pharmacotherapy Vol. 163 ( 2023-07), p. 114870-
    Details
    In: Biomedicine & Pharmacotherapy, Elsevier BV, Vol. 163 ( 2023-07), p. 114870-
    Type of Medium: Online Resource
    ISSN: 0753-3322
    URL: Article
    DOI: 10.1016/j.biopha.2023.114870
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1501510-5
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  • 4
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    Online Resource
    Hydrous icaritin nanorods with excellent stability improves the in vitro and in vivo activity against breast cancer
    Informa UK Limited ; 2020
    In:  Drug Delivery Vol. 27, No. 1 ( 2020-01-01), p. 228-237
    Details
    In: Drug Delivery, Informa UK Limited, Vol. 27, No. 1 ( 2020-01-01), p. 228-237
    Type of Medium: Online Resource
    ISSN: 1071-7544 , 1521-0464
    URL: Article
    DOI: 10.1080/10717544.2020.1716877
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2020593-4
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  • 5
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    Potential mechanisms of hexaconazole resistance in Fusarium graminearum
    Scientific Societies ; 2024
    In:  Plant Disease
    Details
    In: Plant Disease, Scientific Societies
    Abstract: The Fusarium head blight (FHB) caused by Fusarium graminearum is a serious fungal disease that can dramatically impact wheat production. At present, control is mainly achieved by the use of chemical fungicides. Hexaconazole (IUPAC name: 2-(2,4-dichlorophenyl)-1-(1,2,4-triazol-1-yl)hexan-2-ol) is a widely used triazole fungicide, but the sensitivity of F. graminearum to this compound has yet to be established. The current study found that the EC50 values of 83 field isolates of F. graminearum ranged between 0.06 and 4.33 μg/mL, with an average EC50 of 0.78 μg/mL. Assessment of four hexaconazole-resistant laboratory mutants of F. graminearum revealed that their mycelial growth, and pathogenicity were reduced compared to their parental isolates, and that asexual reproduction was reduced by resistance to hexaconazole. Meanwhile, the mutants appeared to be more sensitive to abiotic stress associated with SDS, and H2O2, while their tolerance of high concentration of Congo red, and Na+ and K+ increased. Molecular analysis revealed numerous point mutations in the FgCYP51 target genes that resulted in amino acid substitutions, including L92P and N123S in FgCYP51A, as well as M331V, F62L, Q252R, A412V, and V488A in FgCYP51B, and S28L, S256A, V307A, D287G and R515I in FgCYP51C, three of which (S28L, S256A, and V307A) were conserved in all of the resistant mutants. Furthermore, the expression of the FgCYP51 genes in resistant strains was found to be significantly (p 〈 0.05) reduced compared to their sensitive parental isolates. Positive cross-resistance was found between hexaconazole and metconazole and flutriafol, as well as with the diarylamine fungicide fluazinam, but not with propiconazole, and the phenylpyrrole fungicide fludioxonil, or with tebuconazole, which actually exhibited negative cross-resistance. These results provide valuable insight into resistant mechanisms to triazole fungicides in F. graminearum, as well as the appropriate selection of fungicide combinations for the control of FHB to ensure optimal wheat production.
    Type of Medium: Online Resource
    ISSN: 0191-2917 , 1943-7692
    URL: Article
    DOI: 10.1094/PDIS-04-24-0880-RE
    Language: English
    Publisher: Scientific Societies
    Publication Date: 2024
    detail.hit.zdb_id: 2042679-3
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  • 6
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    Online Resource
    Preparation of high drug-loading celastrol nanosuspensions and their anti-breast cancer activities in vitro and in vivo
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-06-01)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-06-01)
    Abstract: As one of the main components of Tripterygium wilfordii Hook F, celastrol (CSL) has significant antitumor activity, but its clinical application has been limited by its poor solubility, low oral bioavailability and systemic toxicity. In this study, celastrol nanosuspensions (CSL-NSps) were prepared using an antisolvent precipitation method with poloxamer 188 (P-188) as a stabilizer at a high CSL/P-188 feeding ratio of 8:1. The resultant CSL was spherical in shape with an average particle size of 147.9 nm, a polydispersity index (PDI) of 0.12 and zeta potential of -19.2 mV. The encapsulation efficiency and drug loading content were 98.18% and 86.83%, respectively, and the X-ray diffraction (XRD) pattern showed that CSL existed in an amorphous state in the nanosuspensions. CSL-NSps were quite stable in various physiological media and plasma and were both suitable for oral and intravenous administration. Nanosuspensions greatly enhanced the in vitro dissolution, and the cumulative drug release reached approximately 69.20% within 48 h. In vivo , CSL-NSps (3 mg/kg, i.g .) displayed a significantly enhanced tumor inhibition rate (TIR) in comparison with that of CSL suspension when administered orally (TIR, 50.39%, vs. 41.16%, p  〈  0.05),  similar to that of PTX injection (8 mg/kg, i.v . TIR, 50.88%). CSL-NSps showed even better therapeutic efficacy than PTX injection (TIR, 64.18%, p  〈  0.01) when intravenously injected. This has demonstrated that, with the help of nanosuspensions, CSL is likely to be an effective and promising antitumor agent in clinic practice for the treatment of breast cancer.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-65773-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 7
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    Online Resource
    A Low Dose of Hydrous Icaritin Nano-Formulation with Remarkable Efficacy and Tumor Targeting in Cancer Therapy
    American Scientific Publishers ; 2021
    In:  Journal of Biomedical Nanotechnology Vol. 17, No. 10 ( 2021-10-01), p. 2003-2013
    Details
    In: Journal of Biomedical Nanotechnology, American Scientific Publishers, Vol. 17, No. 10 ( 2021-10-01), p. 2003-2013
    Abstract: Background : The use of chemotherapeutic drugs is restricted in the tumor-therapy because of the severely toxic and side effects among most important factors. The active herbal extracts are always used as a high dose while in the tumortherapy to achieve good anti-tumor effects. Hydrous icaritin has a high activity while there are few existing dosage forms as a result of low solubility in water and poor bioavailability. Results : The prepared hydrous icaritin nanorods (DP-HICT NRs) using mPEG 2000 -DSPE as a stabilizer, presented a narrow distribution of particle size with of 217 nm and a properly high drug-loading content of approximately 65.3±1.5%. A low dose of hydrous icaritin nano-formulation shows remarkable efficacy in cancer therapy (tumor inhibition rate: 61.36±10.80%) compared with the same dose of Paclitaxel injection (tumor inhibition rate: 66.80±4.43%), which approved as medicaments. Not only that, DP-HICT NRs can escape the clearance of the immune system and enhance targeting ability to the tumor site with only one excipient and such a low dose. Conclusions : This kind of nanoparticles contain a low dose of HICT used mPEG 2000 -DSPE as a stabilizer, while can achieve good tumor targeting as some active targeting agents and an anti-tumor effect as the PTX injection. There are broad prospects in drug safety, anti-tumor efficacy and even prognosis.
    Type of Medium: Online Resource
    ISSN: 1550-7033
    URL: Article
    DOI: 10.1166/jbn.2021.3176
    Language: English
    Publisher: American Scientific Publishers
    Publication Date: 2021
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  • 8
    Online Resource
    Online Resource
    Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer
    Informa UK Limited ; 2020
    In:  Drug Delivery Vol. 27, No. 1 ( 2020-01-01), p. 816-824
    Details
    In: Drug Delivery, Informa UK Limited, Vol. 27, No. 1 ( 2020-01-01), p. 816-824
    Type of Medium: Online Resource
    ISSN: 1071-7544 , 1521-0464
    URL: Article
    DOI: 10.1080/10717544.2020.1770372
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2020593-4
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  • 9
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    Online Resource
    A comparative study on the in vitro and in vivo antitumor efficacy of icaritin and hydrous icaritin nanorods
    Informa UK Limited ; 2020
    In:  Drug Delivery Vol. 27, No. 1 ( 2020-01-01), p. 1176-1187
    Details
    In: Drug Delivery, Informa UK Limited, Vol. 27, No. 1 ( 2020-01-01), p. 1176-1187
    Type of Medium: Online Resource
    ISSN: 1071-7544 , 1521-0464
    URL: Article
    DOI: 10.1080/10717544.2020.1801892
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2020593-4
    SSG: 15,3
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  • 10
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    Online Resource
    Enhanced tumor accumulation and therapeutic efficacy of liposomal drugs through over-threshold dosing
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Nanobiotechnology Vol. 20, No. 1 ( 2022-03-15)
    Details
    In: Journal of Nanobiotechnology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-03-15)
    Abstract: Most intravenously administered drug-loaded nanoparticles are taken up by liver Kupffer cells, and only a small portion can accumulate at the tumor, resulting in an unsatisfactory therapeutic efficacy and side effects for chemotherapeutic agents. Tumor-targeted drug delivery proves to be the best way to solve this problem; however, the complex synthesis, or surface modification process, together with the astonishing high cost make its clinical translation nearly impossible. Methods Referring to Ouyang’s work and over-threshold dosing theory in general, blank PEGylated liposomes (PEG-Lipo) were prepared and used as tumor delivery enhancers to determine whether they could significantly enhance the tumor accumulation and in vivo antitumor efficacy of co-injected liposomal ACGs (PEG-ACGs-Lipo), a naturally resourced chemotherapeutic. Here, the phospholipid dose was used as an indicator of the number of liposomes particles with similar particle sizes, and the liposomes was labelled with DiR, a near-red fluorescent probe, to trace their in vivo biodistribution. Two mouse models, 4T1-bearing and U87-bearing, were employed for in vivo examination. Results PEG-Lipo and PEG-ACGs-Lipo had similar diameters. At a low-threshold dose (12 mg/kg equivalent phospholipids), PEG-Lipo was mainly distributed in the liver rather than in the tumor, with the relative tumor targeting index (RTTI) being ~ 0.38 at 72 h after administration. When over-threshold was administered (50 mg/kg or 80 mg/kg of equivalent phospholipids), a much higher and quicker drug accumulation in tumors and a much lower drug accumulation in the liver were observed, with the RTTI increasing to ~ 0.9. The in vivo antitumor study in 4T1 tumor-bearing mice showed that, compared to PEG-ACGs-Lipo alone (2.25 mg/kg phospholipids), the co-injection of a large dose of blank PEG-Lipo (50 mg/kg of phospholipids) significantly reduced the tumor volume of the mice by 22.6% ( P   〈  0.05) and enhanced the RTTI from 0.41 to 1.34. The intravenous injection of a low drug loading content (LDLC) of liposomal ACGs (the same dose of ACGs at 50 mg/kg of equivalent phospholipids) achieved a similar tumor inhibition rate (TIR) to that of co-injection. In the U87 MG tumor-bearing mouse model, co-injection of the enhancer also significantly promoted the TIR (83.32% vs. 66.80%, P  〈  0.05) and survival time of PEG-ACGs-Lipo. Conclusion An over-threshold dosing strategy proved to be a simple and feasible way to enhance the tumor delivery and antitumor efficacy of nanomedicines and was benefited to benefit their clinical result, especially for liposomal drugs. Graphical Abstract
    Type of Medium: Online Resource
    ISSN: 1477-3155
    URL: Article
    DOI: 10.1186/s12951-022-01349-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2100022-0
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