Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, P. R. China.
College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding, 071002, P. R. China.
Adv Healthc Mater. 2019 Jul;8(13):e1900160. doi: 10.1002/adhm.201900160. Epub 2019 Apr 10.
Cancer stem cells (CSCs) are responsible for malignant tumor initiation, recurrences, and metastasis. Therefore, targeting CSCs is a promising strategy for the development of cancer therapies. A big challenge for CSC-based cancer therapy is the overexpression of therapeutic stress protein, heat shock protein 90 (Hsp90), which protects CSCs from further therapeutic-induced damage, leading to the failure of treatment. Thus, efficient strategies to target CSCs are urgently needed for cancer therapy. To this end, a multifunctional nanoparticle (MNP) for CSC-based combined thermotherapy and chemotherapy is reported. This strategy dramatically suppresses tumor growth in breast CSC xenograft-bearing mice. Furthermore, a new mechanism is present that the MNP exerts its striking effects on CSCs by inhibiting the secretion of extracellular Hsp90 (eHsp90), resulting in the interruption of several key signaling pathways. These findings open new perspectives on the use of an MNP for effective CSC-based cancer treatment by inhibiting the function of eHsp90.
癌症干细胞（CSCs）是恶性肿瘤起始、复发和转移的根源。因此，针对 CSCs 的治疗策略是癌症治疗发展的一个很有前途的方向。基于 CSC 的癌症治疗的一个主要挑战是治疗应激蛋白热休克蛋白 90（Hsp90）的过度表达，它保护 CSCs 免受进一步的治疗诱导性损伤，导致治疗失败。因此，迫切需要针对 CSCs 的有效治疗策略。为此，报道了一种用于基于 CSC 的联合热疗和化疗的多功能纳米颗粒（MNP）。该策略可显著抑制乳腺癌 CSC 异种移植瘤小鼠的肿瘤生长。此外，存在一种新的机制，即 MNP 通过抑制细胞外 Hsp90（eHsp90）的分泌来发挥对 CSCs 的显著作用，从而中断几个关键信号通路。这些发现为通过抑制 eHsp90 的功能来有效治疗基于 CSC 的癌症提供了新的视角。
