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西妥昔单抗偶联亚硒酸钠纳米粒用于阿霉素靶向递送至 MCF-7 乳腺癌细胞。

Cetuximab-conjugated sodium selenite nanoparticles for doxorubicin targeted delivery against MCF-7 breast cancer cells.

机构信息

Department of Pharmaceutics, College of Parmacy, Jazan University, Jazan, 45142, Saudi Arabia.

Health Research Centre, Jazan University, Jazan, 45142, Saudi Arabia.

出版信息

Nanomedicine (Lond). 2024;19(29):2447-2462. doi: 10.1080/17435889.2024.2403962. Epub 2024 Oct 9.

Abstract

To develop and characterize doxorubicin-loaded sodium selenite nanoparticles (SSNP-DOX) and their surface attachment with cetuximab (mAb-SSNP-DOX). SSNP-DOX was formulated by gelation and then conjugated with cetuximab to form mAb-SSNP-DOX. Characterization included DLS, SEM, TEM, DSC, Raman spectroscopy and XRD. , the kinetics of doxorubicin release and cytotoxicity in MCF-7 breast cancer cells were investigated. The zeta potential for SSNP-DOX and mAb-SSNP-DOX was -14.4 ± 10.1 mV and -27.5 ± 7.28 mV, with particle sizes of 181.3 nm and 227.5 nm, respectively. The formulation intensity was 89.7% for SSNP-DOX and 100% for mAb-SSNP-DOX, with PDI values of 0.419 and 0.251, respectively. SEM and TEM showed that mAb-SSNP-DOX was smooth and spherical. The DSC analysis revealed exothermic peaks at 102.44°C for SSNP-DOX and 144.21°C for mAb-SSNP-DOX, along with endothermic peaks at 269.19°C and 241.6°C, respectively. Raman spectroscopy showed a higher intensity for mAb-SSNP-DOX. The XRD study showed different peaks for each formulation. Both followed zero order kinetics for doxorubicin release. Cytotoxicity studies showed significant effects and high apoptosis in MCF-7 cells for both formulations. The mAb-SSNP-DOX showed promising properties, more effective doxorubicin release and higher cytotoxicity against breast cancer cells compared with SSNP-DOX.

摘要

研制并表征阿霉素负载亚硒酸钠纳米粒(SSNP-DOX)及其表面连接西妥昔单抗(mAb-SSNP-DOX)。SSNP-DOX 通过凝胶化形成,然后与西妥昔单抗偶联形成 mAb-SSNP-DOX。对其进行了 DLS、SEM、TEM、DSC、拉曼光谱和 XRD 等表征。考察了 DOX 的释放动力学及 MCF-7 乳腺癌细胞的细胞毒性。SSNP-DOX 和 mAb-SSNP-DOX 的zeta 电位分别为-14.4±10.1 mV 和-27.5±7.28 mV,粒径分别为 181.3nm 和 227.5nm。SSNP-DOX 的包封率为 89.7%,mAb-SSNP-DOX 为 100%,PDI 值分别为 0.419 和 0.251。SEM 和 TEM 显示 mAb-SSNP-DOX 光滑且呈球形。DSC 分析表明 SSNP-DOX 有 102.44°C 的放热峰,mAb-SSNP-DOX 有 144.21°C 的放热峰,分别对应 269.19°C 和 241.6°C 的吸热峰。拉曼光谱显示 mAb-SSNP-DOX 的强度更高。XRD 研究显示两种制剂均有不同的特征峰。DOX 释放均遵循零级动力学。细胞毒性研究表明,两种制剂对 MCF-7 细胞均有显著作用和较高的凋亡率。与 SSNP-DOX 相比,mAb-SSNP-DOX 显示出更好的性质,对 DOX 的释放更有效,对乳腺癌细胞的细胞毒性更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8a/11520552/6c6ec662dda9/INNM_A_2403962_F0001_C.jpg

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