SLNP-based CDK4- targeted nanotherapy against glioblastoma
IntroductionGlioblastoma is a grade IV solid brain tumor and has a 15-month survival rate even after treatment. Glioblastoma development is heavily influenced by retinoblastoma protein (pRB) pathway changes. The blood–brain barrier, drug resistance, and severe toxicity of Temozolamide are key obstac...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1455816/full |
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| author | Uzma Ghani Fareeha Khalid Ghori Muhammad Usman Qamar Muhammad Usman Qamar Hina Khan Basit Azad Sabahat Habib Saira Justin Ishaq N. Khan Ishaq N. Khan Tawaf Ali Shah Gamal A. Shazly Mohammed Bourhia Fouzia Perveen Aneela Javed |
| author_facet | Uzma Ghani Fareeha Khalid Ghori Muhammad Usman Qamar Muhammad Usman Qamar Hina Khan Basit Azad Sabahat Habib Saira Justin Ishaq N. Khan Ishaq N. Khan Tawaf Ali Shah Gamal A. Shazly Mohammed Bourhia Fouzia Perveen Aneela Javed |
| author_sort | Uzma Ghani |
| collection | DOAJ |
| description | IntroductionGlioblastoma is a grade IV solid brain tumor and has a 15-month survival rate even after treatment. Glioblastoma development is heavily influenced by retinoblastoma protein (pRB) pathway changes. The blood–brain barrier, drug resistance, and severe toxicity of Temozolamide are key obstacles in treating glioblastoma. Innovative treatments targeting the pRB pathway with efficient delivery vehicles are required to treat glioblastoma.MethodsFor this purpose, a library of 691 plant extracts previously tested in vitro for anti-cancerous, anti inflammatory, and anti-proliferative characteristics was created after thorough literature investigations. Compounds were docked against pRB pathway protein ligands using molecular operating environment and chimera. Their nuclear structure and drug-like properties were predicted through Lipinski rule and density functional theory analysis. Physio-chemical characterizations of naked and drug-encapsulated SLNPs assessed size, stability, entrapment efficiency, and drug release rate. Anti-cancer potential of drug and drug- loaded SLNPs was evaluated using U87, U251, and HEK cell lines. Formulations were tested for cancer cell metastatic potential using cell migration assays.ResultsSilymarin (Sil) was identified as the most potent compound against CDK4, which was then encapsulated in stearic acid solid lipid nanoparticles (SLNP-Sil). Sil showed decreased cell viability 72 h after treatment against both U87 and U251 cell lines but had negligible cytotoxic effect on HEK-293. IC50 value of Sil was 155.14 µM for U87 and 195.93 µM for U251. Sil and SLNP-Sil effectively inhibited U87 and U251 cell migration 24 h after treatment.DiscussionOur results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit in vivo experimental verification using orthotropic xenograft mouse models against glioblastoma. |
| format | Article |
| id | doaj-art-a5a0d5826a4f4a96a741c064f6c90e86 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-a5a0d5826a4f4a96a741c064f6c90e862024-11-22T05:10:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-11-011410.3389/fonc.2024.14558161455816SLNP-based CDK4- targeted nanotherapy against glioblastomaUzma Ghani0Fareeha Khalid Ghori1Muhammad Usman Qamar2Muhammad Usman Qamar3Hina Khan4Basit Azad5Sabahat Habib6Saira Justin7Ishaq N. Khan8Ishaq N. Khan9Tawaf Ali Shah10Gamal A. Shazly11Mohammed Bourhia12Fouzia Perveen13Aneela Javed14Molecular Immunology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, PakistanMolecular Immunology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, PakistanInstitute of Microbiology, Faculty of Life Sciences, Government College University Faisalabad, Faisalabad, PakistanDivision of Infectious Disease and Department of Medicine, University of Geneva, Geneva, SwitzerlandMolecular Immunology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, PakistanMaterials And Modeling Lab, School of Interdisciplinary Engineering and Sciences, National University of Sciences and Technology, Islamabad, PakistanMolecular Immunology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, PakistanMolecular Immunology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, PakistanCancer Cell Culture and Precision Oncomedicine Lab, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, PakistanDepartment of Pharmaceutical Sciences, Taxes A&M Health Science Center, Joe H. Reynolds Medical Sciences Build, College Station, TX, United StatesCollege of Agriculture Engineering and Food Sciences, Shandong University of Technology, Zibo, ChinaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, MoroccoMaterials And Modeling Lab, School of Interdisciplinary Engineering and Sciences, National University of Sciences and Technology, Islamabad, PakistanMolecular Immunology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, PakistanIntroductionGlioblastoma is a grade IV solid brain tumor and has a 15-month survival rate even after treatment. Glioblastoma development is heavily influenced by retinoblastoma protein (pRB) pathway changes. The blood–brain barrier, drug resistance, and severe toxicity of Temozolamide are key obstacles in treating glioblastoma. Innovative treatments targeting the pRB pathway with efficient delivery vehicles are required to treat glioblastoma.MethodsFor this purpose, a library of 691 plant extracts previously tested in vitro for anti-cancerous, anti inflammatory, and anti-proliferative characteristics was created after thorough literature investigations. Compounds were docked against pRB pathway protein ligands using molecular operating environment and chimera. Their nuclear structure and drug-like properties were predicted through Lipinski rule and density functional theory analysis. Physio-chemical characterizations of naked and drug-encapsulated SLNPs assessed size, stability, entrapment efficiency, and drug release rate. Anti-cancer potential of drug and drug- loaded SLNPs was evaluated using U87, U251, and HEK cell lines. Formulations were tested for cancer cell metastatic potential using cell migration assays.ResultsSilymarin (Sil) was identified as the most potent compound against CDK4, which was then encapsulated in stearic acid solid lipid nanoparticles (SLNP-Sil). Sil showed decreased cell viability 72 h after treatment against both U87 and U251 cell lines but had negligible cytotoxic effect on HEK-293. IC50 value of Sil was 155.14 µM for U87 and 195.93 µM for U251. Sil and SLNP-Sil effectively inhibited U87 and U251 cell migration 24 h after treatment.DiscussionOur results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit in vivo experimental verification using orthotropic xenograft mouse models against glioblastoma.https://www.frontiersin.org/articles/10.3389/fonc.2024.1455816/fullblood brain barrierglioblastomasilymarinsolid lipid nanoparticlestemozolamide |
| spellingShingle | Uzma Ghani Fareeha Khalid Ghori Muhammad Usman Qamar Muhammad Usman Qamar Hina Khan Basit Azad Sabahat Habib Saira Justin Ishaq N. Khan Ishaq N. Khan Tawaf Ali Shah Gamal A. Shazly Mohammed Bourhia Fouzia Perveen Aneela Javed SLNP-based CDK4- targeted nanotherapy against glioblastoma Frontiers in Oncology blood brain barrier glioblastoma silymarin solid lipid nanoparticles temozolamide |
| title | SLNP-based CDK4- targeted nanotherapy against glioblastoma |
| title_full | SLNP-based CDK4- targeted nanotherapy against glioblastoma |
| title_fullStr | SLNP-based CDK4- targeted nanotherapy against glioblastoma |
| title_full_unstemmed | SLNP-based CDK4- targeted nanotherapy against glioblastoma |
| title_short | SLNP-based CDK4- targeted nanotherapy against glioblastoma |
| title_sort | slnp based cdk4 targeted nanotherapy against glioblastoma |
| topic | blood brain barrier glioblastoma silymarin solid lipid nanoparticles temozolamide |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1455816/full |
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