Enhancing glioblastoma cytotoxicity through encapsulating O6-benzylguanine and temozolomide in PEGylated liposomal nanocarrier: an in vitro study.

IF 2.6 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2024-11-01 Epub Date: 2024-10-23 DOI:10.1007/s13205-024-04123-2

Manasa Manjunath Hegde, Pranoti Palkar, Sadhana P Mutalik, Srinivas Mutalik, Jayant Sastri Goda, B S Satish Rao

{"title":"Enhancing glioblastoma cytotoxicity through encapsulating O6-benzylguanine and temozolomide in PEGylated liposomal nanocarrier: an in vitro study.","authors":"Manasa Manjunath Hegde, Pranoti Palkar, Sadhana P Mutalik, Srinivas Mutalik, Jayant Sastri Goda, B S Satish Rao","doi":"10.1007/s13205-024-04123-2","DOIUrl":null,"url":null,"abstract":"Glioblastoma (GBM) (grade IV glioma) is the most fatal brain tumor, with a median survival of just 14 months despite current treatments. Temozolomide (TMZ), an alkylating agent used with radiation, faces challenges such as systemic toxicity, poor absorption, and drug resistance. To enhance TMZ effectiveness, we developed poly(ethylene glycol) (PEG) liposomes co-loaded with TMZ and O6-benzylguanine (O6-BG) for targeted glioma therapy. These liposomes, prepared using the thin-layer hydration method, had an average size of 146.33 ± 6.75 nm and a negative zeta potential (-49.6 ± 3.1 mV). Drug release was slower at physiological pH, with 66.84 ± 4.62% of TMZ and 69.70 ± 2.88% of O6-BG released, indicating stability at physiological conditions. The liposomes showed significantly higher cellular uptake (p < 0.05) than the free dye. The dual drug-loaded liposomes exhibited superior cytotoxicity against U87 glioma cells, with a lower IC50 value (3.99µg/mL) than the free drug combination, demonstrating enhanced anticancer efficacy. The liposome formulation induced higher apoptosis (19.42 ± 3.5%) by causing sub-G0/G1 cell cycle arrest. The novelty of our study lies in co-encapsulating TMZ and O6-BG within PEGylated liposomes, effectively overcoming drug resistance and improving targeted delivery for glioma treatment.Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04123-2.","PeriodicalId":7067,"journal":{"name":"3 Biotech","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499494/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"3 Biotech","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s13205-024-04123-2","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Glioblastoma (GBM) (grade IV glioma) is the most fatal brain tumor, with a median survival of just 14 months despite current treatments. Temozolomide (TMZ), an alkylating agent used with radiation, faces challenges such as systemic toxicity, poor absorption, and drug resistance. To enhance TMZ effectiveness, we developed poly(ethylene glycol) (PEG) liposomes co-loaded with TMZ and O6-benzylguanine (O6-BG) for targeted glioma therapy. These liposomes, prepared using the thin-layer hydration method, had an average size of 146.33 ± 6.75 nm and a negative zeta potential (-49.6 ± 3.1 mV). Drug release was slower at physiological pH, with 66.84 ± 4.62% of TMZ and 69.70 ± 2.88% of O6-BG released, indicating stability at physiological conditions. The liposomes showed significantly higher cellular uptake (p < 0.05) than the free dye. The dual drug-loaded liposomes exhibited superior cytotoxicity against U87 glioma cells, with a lower IC₅₀ value (3.99µg/mL) than the free drug combination, demonstrating enhanced anticancer efficacy. The liposome formulation induced higher apoptosis (19.42 ± 3.5%) by causing sub-G0/G1 cell cycle arrest. The novelty of our study lies in co-encapsulating TMZ and O6-BG within PEGylated liposomes, effectively overcoming drug resistance and improving targeted delivery for glioma treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04123-2.

查看原文本刊更多论文

通过在 PEG 化脂质体纳米载体中封装 O6-苄基鸟嘌呤和替莫唑胺来增强胶质母细胞瘤的细胞毒性：一项体外研究。

胶质母细胞瘤（GBM）（IV 级胶质瘤）是最致命的脑肿瘤，尽管目前有多种治疗方法，但中位生存期仅为 14 个月。替莫唑胺（TMZ）是一种与放射线配合使用的烷化剂，它面临着全身毒性、吸收不良和耐药性等挑战。为了提高TMZ的疗效，我们开发了共载TMZ和O6-苄基鸟嘌呤（O6-BG）的聚乙二醇（PEG）脂质体，用于胶质瘤的靶向治疗。这些脂质体采用薄层水合法制备，平均尺寸为 146.33 ± 6.75 nm，Zeta 电位为负（-49.6 ± 3.1 mV）。在生理 pH 值下，药物释放速度较慢，TMZ 和 O6-BG 的释放量分别为 66.84 ± 4.62% 和 69.70 ± 2.88%，这表明脂质体在生理条件下是稳定的。脂质体的细胞吸收率（p 50 值（3.99µg/mL））明显高于游离药物组合，表明抗癌功效增强。脂质体制剂通过引起亚 G0/G1 细胞周期停滞，诱导更多细胞凋亡（19.42 ± 3.5%）。我们研究的新颖之处在于将TMZ和O6-BG共同包裹在PEG化脂质体中，有效克服了耐药性，提高了胶质瘤治疗的靶向给药效果：在线版本包含补充材料，可查阅 10.1007/s13205-024-04123-2。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.