{"title":"评估双药9-羟甲基诺斯卡平和负载替米沙坦的硬脂酸纳米颗粒抗(H1299)非小细胞肺癌及其与牛血清白蛋白†的机制相互作用","authors":"Snigdha Singh, Shubham Sewariya, Tanya Goel, Sagar Panchal, Aarushi Singh, Shrikant Kukreti, Manisha Tiwari and Ramesh Chandra","doi":"10.1039/D4MA00958D","DOIUrl":null,"url":null,"abstract":"<p >Solid lipid nanoparticles are appealing to the scientific community owing to their expedient and versatile nature as systems for drug delivery and therefore are being used to treat a variety of illnesses. With parallel line of thought, herein, we have reported the synthesis and characterisation of dual drug stearic acid-loaded solid lipid nanoparticles and screened their efficacy in non-small cell lung cancer. The desired nanoparticles, namely 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLNs, were prepared using the solvent diffusion method. TEM and AFM images revealed that the nanoparticles have spherical form with a mean size of 36.6 nm. The nanostructures' zeta potential and hydrodynamic size were found to be −36.23 mV and ∼406.8 nm, respectively. From RP-HPLC, the noscapine and telmisartan loaded in the nanoparticles were found to be 1.86% and 1.97% respectively. Additionally, we have probed into the interaction of BSA with the synthesized nanocomposite using UV-visible, fluorescence and CD spectroscopic techniques along with computational techniques, namely molecular docking, molecular dynamic simulations and MM-PBSA/GBSA calculations. From the fluorescence quenching of BSA upon interaction with the SLNs, we deduced that a stable ground-state complex between 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLN and BSA was formed. Similarly, <em>in silico</em> evaluation indicated formation of a stable dual drug complex with BSA with telmisartan being more compatible for binding to the protein. To assess further, we also evaluated the anticancer property of 9-CH<small><sub>2</sub></small>OH noscapine, telmisartan and 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLN against H1299 lung cancer cell line using MTT assay and the calculated IC<small><sub>50</sub></small> of 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLN was 186 μg mL<small><sup>−1</sup></small>. Overall, based on the promising results in this research, such SLNs could be a promising drug delivery tool and can be crucial in the conversion of potential anticancer drugs to marketed anticancer drugs in the near future.</p>","PeriodicalId":18242,"journal":{"name":"Materials Advances","volume":" 4","pages":" 1364-1378"},"PeriodicalIF":4.7000,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/ma/d4ma00958d?page=search","citationCount":"0","resultStr":"{\"title\":\"Assessing dual drug 9-hydroxymethyl noscapine and telmisartan-loaded stearic acid nanoparticles against (H1299) non-small cell lung cancer and their mechanistic interaction with bovine serum albumin†\",\"authors\":\"Snigdha Singh, Shubham Sewariya, Tanya Goel, Sagar Panchal, Aarushi Singh, Shrikant Kukreti, Manisha Tiwari and Ramesh Chandra\",\"doi\":\"10.1039/D4MA00958D\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Solid lipid nanoparticles are appealing to the scientific community owing to their expedient and versatile nature as systems for drug delivery and therefore are being used to treat a variety of illnesses. With parallel line of thought, herein, we have reported the synthesis and characterisation of dual drug stearic acid-loaded solid lipid nanoparticles and screened their efficacy in non-small cell lung cancer. The desired nanoparticles, namely 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLNs, were prepared using the solvent diffusion method. TEM and AFM images revealed that the nanoparticles have spherical form with a mean size of 36.6 nm. The nanostructures' zeta potential and hydrodynamic size were found to be −36.23 mV and ∼406.8 nm, respectively. From RP-HPLC, the noscapine and telmisartan loaded in the nanoparticles were found to be 1.86% and 1.97% respectively. Additionally, we have probed into the interaction of BSA with the synthesized nanocomposite using UV-visible, fluorescence and CD spectroscopic techniques along with computational techniques, namely molecular docking, molecular dynamic simulations and MM-PBSA/GBSA calculations. From the fluorescence quenching of BSA upon interaction with the SLNs, we deduced that a stable ground-state complex between 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLN and BSA was formed. Similarly, <em>in silico</em> evaluation indicated formation of a stable dual drug complex with BSA with telmisartan being more compatible for binding to the protein. To assess further, we also evaluated the anticancer property of 9-CH<small><sub>2</sub></small>OH noscapine, telmisartan and 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLN against H1299 lung cancer cell line using MTT assay and the calculated IC<small><sub>50</sub></small> of 9-CH<small><sub>2</sub></small>OH Nos-Tel-SLN was 186 μg mL<small><sup>−1</sup></small>. Overall, based on the promising results in this research, such SLNs could be a promising drug delivery tool and can be crucial in the conversion of potential anticancer drugs to marketed anticancer drugs in the near future.</p>\",\"PeriodicalId\":18242,\"journal\":{\"name\":\"Materials Advances\",\"volume\":\" 4\",\"pages\":\" 1364-1378\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-01-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.rsc.org/en/content/articlepdf/2025/ma/d4ma00958d?page=search\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Materials Advances\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2025/ma/d4ma00958d\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Materials Advances","FirstCategoryId":"1085","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2025/ma/d4ma00958d","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
固体脂质纳米颗粒由于其作为药物输送系统的方便性和多用途性而受到科学界的青睐,因此被用于治疗各种疾病。在此,我们报道了双药硬脂酸负载固体脂质纳米颗粒的合成和表征,并筛选了它们在非小细胞肺癌中的疗效。采用溶剂扩散法制备了所需的9-CH2OH Nos-Tel-SLNs纳米颗粒。透射电镜(TEM)和原子力显微镜(AFM)图像显示,纳米颗粒呈球形,平均尺寸为36.6 nm。纳米结构的zeta电位和水动力尺寸分别为−36.23 mV和~ 406.8 nm。反相高效液相色谱(RP-HPLC)结果显示,纳米颗粒中诺斯卡平和替米沙坦的含量分别为1.86%和1.97%。此外,我们利用紫外可见、荧光和CD光谱技术以及计算技术,即分子对接、分子动力学模拟和MM-PBSA/GBSA计算,探讨了BSA与合成的纳米复合材料的相互作用。根据BSA与sln相互作用后的荧光猝灭,我们推断9-CH2OH no - tel - sln与BSA之间形成了稳定的基态配合物。同样,计算机评价表明与BSA形成稳定的双药复合物,替米沙坦与蛋白质结合更相容。为了进一步评价9-CH2OH noscapine、替米沙坦和9-CH2OH Nos-Tel-SLN对H1299肺癌细胞株的抗癌作用,采用MTT法测定了9-CH2OH Nos-Tel-SLN的IC50为186 μg mL−1。总的来说,基于本研究的有希望的结果,这种sln可能是一种有希望的药物递送工具,并且在不久的将来可能在潜在的抗癌药物转化为上市的抗癌药物方面发挥关键作用。
Assessing dual drug 9-hydroxymethyl noscapine and telmisartan-loaded stearic acid nanoparticles against (H1299) non-small cell lung cancer and their mechanistic interaction with bovine serum albumin†
Solid lipid nanoparticles are appealing to the scientific community owing to their expedient and versatile nature as systems for drug delivery and therefore are being used to treat a variety of illnesses. With parallel line of thought, herein, we have reported the synthesis and characterisation of dual drug stearic acid-loaded solid lipid nanoparticles and screened their efficacy in non-small cell lung cancer. The desired nanoparticles, namely 9-CH2OH Nos-Tel-SLNs, were prepared using the solvent diffusion method. TEM and AFM images revealed that the nanoparticles have spherical form with a mean size of 36.6 nm. The nanostructures' zeta potential and hydrodynamic size were found to be −36.23 mV and ∼406.8 nm, respectively. From RP-HPLC, the noscapine and telmisartan loaded in the nanoparticles were found to be 1.86% and 1.97% respectively. Additionally, we have probed into the interaction of BSA with the synthesized nanocomposite using UV-visible, fluorescence and CD spectroscopic techniques along with computational techniques, namely molecular docking, molecular dynamic simulations and MM-PBSA/GBSA calculations. From the fluorescence quenching of BSA upon interaction with the SLNs, we deduced that a stable ground-state complex between 9-CH2OH Nos-Tel-SLN and BSA was formed. Similarly, in silico evaluation indicated formation of a stable dual drug complex with BSA with telmisartan being more compatible for binding to the protein. To assess further, we also evaluated the anticancer property of 9-CH2OH noscapine, telmisartan and 9-CH2OH Nos-Tel-SLN against H1299 lung cancer cell line using MTT assay and the calculated IC50 of 9-CH2OH Nos-Tel-SLN was 186 μg mL−1. Overall, based on the promising results in this research, such SLNs could be a promising drug delivery tool and can be crucial in the conversion of potential anticancer drugs to marketed anticancer drugs in the near future.