Xue Chen, Haopeng Wan, Lijuan Lu, Ran Li, Bo Sun, Juan Ren
{"title":"PLGA-PEG-c(RGDfK)-Kushenol E Micelles With a Therapeutic Potential for Targeting Ovarian Cancer","authors":"Xue Chen, Haopeng Wan, Lijuan Lu, Ran Li, Bo Sun, Juan Ren","doi":"10.1049/nbt2/7136323","DOIUrl":null,"url":null,"abstract":"<div>\n <p><b>Background:</b> As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from <i>Sophora flavescens</i>, which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor-targeting nanoparticle system modified with tumor-homing c(RGDfK) peptides.</p>\n <p><b>Materials and Methods:</b> In the current study, poly(lactic-co-glycolic acid)-poly(ethylene glycol)-modified with cyclic RGDfK peptide (PLGA-PEG-c(RGDfK))-KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor-active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV-3 cells and xenograft models in BALB/c nude mice.</p>\n <p><b>Results:</b> The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV-3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration-dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site.</p>\n <p><b>Conclusion:</b> The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.</p>\n </div>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"2024 1","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1049/nbt2/7136323","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"IET nanobiotechnology","FirstCategoryId":"5","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1049/nbt2/7136323","RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from Sophora flavescens, which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor-targeting nanoparticle system modified with tumor-homing c(RGDfK) peptides.
Materials and Methods: In the current study, poly(lactic-co-glycolic acid)-poly(ethylene glycol)-modified with cyclic RGDfK peptide (PLGA-PEG-c(RGDfK))-KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor-active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV-3 cells and xenograft models in BALB/c nude mice.
Results: The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV-3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration-dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site.
Conclusion: The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.
期刊介绍:
Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level.
Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries.
IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to:
Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques)
Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology
Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools)
Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles)
Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance
Techniques for probing cell physiology, cell adhesion sites and cell-cell communication
Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology
Societal issues such as health and the environment
Special issues. Call for papers:
Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf
Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf