Scholarlink

<p>Treatments of triple-negative breast cancer (TNBC) using small-molecule tyrosine kinase inhibitors (smTKIs) such as dasatinib (DTB), lenvatinib (LTB), and sorafenib (SFB) are limited by systemic toxicities, poor solubility hindering bioavailability, and the development of treatment resistance over time, warranting the need for improved delivery strategies. To address these limitations, bovine serum albumin (BSA) was employed as a nanoplatform to load three smTKIs (AbNPs) using the desolvation method. The process was further optimised using the design of experiment (DoE) approach. An in-silico docking study revealed strong interactions between smTKIs and BSA, as well as significant interactions with the caspase-7 (Cas-7) apoptosis protein, supporting their therapeutic relevance. AbNPs exhibited a particle size between 54 and 109&#xa0;nm, with a monodispersed and slightly anionic surface charge, and a high entrapment efficiency (61–92%), sustaining drug release at tumour-microenvironment pH. Coumarin-6-loaded AbNPs demonstrated improved cellular uptake in the MDA-MB-231 cell line-based 3D spheroid model, while the cytotoxicity study demonstrated reduced IC<sub>50</sub> values with a 1.5–2.3-fold decrease in spheroid volume when compared to free smTKIs. Overall, our study shows that AbNPs are an efficient delivery system of smTKIs, offering sustained drug release charcterstics, higher cellular uptake, and higher cytotoxicity with significant translational promise for improving triple-negative breast cancer treatment.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Impact of Small Molecule Tyrosine Kinase Inhibitors Loaded Albumin-Based Nanoplatform on Triple Negative Breast Cancer Spheroid Model: an in Silico and in Vitro Study

  • 期刊论文

  • 发表日期：

    2026年2月19日

查看全文
  • Soumyadip Mukherjee,
  • Ankaj Kumar,
  • Rahul Kharat,
  • Saurabh Jadhav,
  • Vishal Kumar,
  • Uday Kiran Roopavath,
  • Arvind Gulbake

摘要

Treatments of triple-negative breast cancer (TNBC) using small-molecule tyrosine kinase inhibitors (smTKIs) such as dasatinib (DTB), lenvatinib (LTB), and sorafenib (SFB) are limited by systemic toxicities, poor solubility hindering bioavailability, and the development of treatment resistance over time, warranting the need for improved delivery strategies. To address these limitations, bovine serum albumin (BSA) was employed as a nanoplatform to load three smTKIs (AbNPs) using the desolvation method. The process was further optimised using the design of experiment (DoE) approach. An in-silico docking study revealed strong interactions between smTKIs and BSA, as well as significant interactions with the caspase-7 (Cas-7) apoptosis protein, supporting their therapeutic relevance. AbNPs exhibited a particle size between 54 and 109 nm, with a monodispersed and slightly anionic surface charge, and a high entrapment efficiency (61–92%), sustaining drug release at tumour-microenvironment pH. Coumarin-6-loaded AbNPs demonstrated improved cellular uptake in the MDA-MB-231 cell line-based 3D spheroid model, while the cytotoxicity study demonstrated reduced IC50 values with a 1.5–2.3-fold decrease in spheroid volume when compared to free smTKIs. Overall, our study shows that AbNPs are an efficient delivery system of smTKIs, offering sustained drug release charcterstics, higher cellular uptake, and higher cytotoxicity with significant translational promise for improving triple-negative breast cancer treatment.