A polymeric nanocarrier that eradicates breast cancer stem cells and delivers chemotherapeutic drugs.

IF 8.1 Q1 ENGINEERING, BIOMEDICAL

Biomaterials research Pub Date : 2023-12-15 DOI:10.1186/s40824-023-00465-9

Li Lv, Yonghui Shi, Zhicheng Deng, Jiajia Xu, Zicong Ye, Jianxiong He, Guanghui Chen, Xiaoxia Yu, Junyan Wu, Xingzhen Huang, Guocheng Li

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Abstract

Background: Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs.

Methods: Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs.

Results: Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway.

Conclusion: HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.

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一种能消灭乳腺癌干细胞并输送化疗药物的聚合物纳米载体。

背景：在临床上，药物纳米载体可显著降低封装化疗药物的毒性和副作用。然而，这些药物纳米载体对根除乳腺癌干细胞（BCSCs）效果甚微。方法：在此，我们合成了一种聚合物纳米载体--透明质酸-块-聚（姜黄素-二硫代二丙酸）（HA-b-PCDA），并探索了利用HA-b-PCDA同时递送化疗药物和根除乳腺癌干细胞的方法：基于分子对接和分子动力学研究，HA-b-PCDA可递送35种临床化疗药物。为了进一步验证HA-b-PCDA的载药能力，研究人员以多柔比星、紫杉醇、多西他赛、吉西他滨和喜树碱为模型药物制备纳米颗粒。这些载药HA-b-PCDA纳米粒子能显著抑制富集了 BCSC 的 4T1 哺乳动物球的增殖和干性。此外，载药HA-b-PCDA纳米颗粒还能有效抑制肿瘤生长，并在体内消灭约95%的BCSCs。最后，HA-b-PCDA通过激活Hippo和抑制JAK2/STAT3通路根除BCSCs：结论：HA-b-PCDA 是一种聚合物纳米载体，可消灭 BCSCs，并有可能输送多种临床化疗药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Biomaterials research

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