Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
J Control Release. 2021 Feb 10;330:1106-1117. doi: 10.1016/j.jconrel.2020.11.015. Epub 2020 Nov 12.
Multidrug resistance (MDR) of cancer stem cells (CSCs) is a major hurdle to chemotherapy, and it is very important to develop CSCs-specific targeted nanocarriers for the treatment of drug resistant CSCs. In this work, we developed CSCs-specific targeted mSiO-dPG nanocarriers simultaneous delivery chemotherapy drug DOX along with the P-glycoprotein (P-gp) inhibitor tariquidar (Tar) for enhanced chemotherapy to overcome MDR in breast CSCs. The mSiO-dPG nanocarriers possess a high loading capability, excellent pH stimuli-responsive performance, and good biocompatibility. With the help of CSCs-specific targeting and P-gp inhibitor Tar, the accumulation of DOX delivered by the mSiO-dPG nanocarriers could be greatly increased in drug resistant three-dimensional mammosphere of breast CSCs, and the chemotherapeutic efficacy against breast CSCs was enhanced. Moreover, the expression of stemness-associated gene and tumorspheres' formation ability was also significantly suppressed, which indicates the excellent capability for overcoming MDR of breast CSCs. Taken together, we developed a CSCs-specific targeted mSiO-dPG nanocarriers for co-delivery DOX and Tar, which provide a promising approach to effectively eliminate the CSCs and overcome the MDR of breast CSCs.
多药耐药（MDR）的癌症干细胞（CSCs）是化疗的主要障碍，因此开发针对 CSCs 的靶向纳米载体对于治疗耐药 CSCs 非常重要。在这项工作中，我们开发了针对 CSCs 的靶向 mSiO-dPG 纳米载体，同时递送达泊西汀（DOX）和 P-糖蛋白（P-gp）抑制剂他利喹达（Tar），以增强化疗来克服乳腺癌 CSCs 的多药耐药性。mSiO-dPG 纳米载体具有高载药能力、优异的 pH 刺激响应性能和良好的生物相容性。在 CSCs 特异性靶向和 P-gp 抑制剂 Tar 的帮助下，mSiO-dPG 纳米载体递送的 DOX 在耐药性乳腺癌 CSCs 的三维球体中的积累可以大大增加，并且增强了对乳腺癌 CSCs 的化疗疗效。此外，还显著抑制了干性相关基因的表达和肿瘤球的形成能力，这表明其具有出色的克服乳腺癌 CSCs 多药耐药性的能力。总之，我们开发了一种针对 CSCs 的靶向 mSiO-dPG 纳米载体，用于共递达 DOX 和 Tar，为有效消除 CSCs 和克服乳腺癌 CSCs 的 MDR 提供了一种有前途的方法。
