Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China,.
J Control Release. 2021 Dec 10;340:282-291. doi: 10.1016/j.jconrel.2021.10.029. Epub 2021 Nov 2.
Targeting breast cancer stem cells (BCSCs) therapy is a prospective strategy to eliminate tumors owing to the BCSCs-governed drug resistance, tumor progression and metastasis. BCSCs are intrinsically in a disequilibrium state with favorable ability of self-renewal rather than differentiation, resulting in inability of complete tumor eradication. Besides the original BCSCs, epithelial-mesenchymal transition (EMT) process can further facilitate BCSCs regeneration, accompanied by tumor progression and metastasis. Herein, we, for the first time, engineered a photodynamic nanoplatform to manipulate BCSCs against tumor progression and metastasis by not only remolding the disequilibrium state but also blocking the EMT process. The HP@PP was constructed by haloperidol (HP)-incorporated polyethyleneimine-polyhistidine (PP) micelles, which was further integrated with low molecular weight heparin (LMWH)-chlorin e6 (Ce6) conjugate (LC) to form HP@PP/LC nanoparticles (NPs). For HP@PP/LC NPs, the protonation of PP in tumor tissues precisely targeted HP to BCSCs for remolding the disequilibrium state via promoting BCSCs differentiation into tumor cells. Simultaneously, LC conjugate targeted to tumors for exerting EMT blocking ability with LMWH, as well as exerting photodynamic clearance of tumor cells with Ce6 component. Therefore, our nanoplatform provides an emerging strategy for manipulating BCSCs against tumor progression and metastasis, demonstrating a promising photodynamic platform against tumors.
靶向乳腺癌干细胞（BCSCs）治疗是一种有前途的策略，可以消除肿瘤，因为 BCSCs 控制的耐药性、肿瘤进展和转移。BCSCs 本质上处于一种失衡状态，具有良好的自我更新能力而不是分化能力，导致无法完全消除肿瘤。除了原始的 BCSCs 之外，上皮-间充质转化（EMT）过程还可以进一步促进 BCSCs 的再生，伴随着肿瘤的进展和转移。在这里，我们首次设计了一种光动力纳米平台，通过重塑失衡状态和阻断 EMT 过程来操纵 BCSCs 以对抗肿瘤的进展和转移。HP@PP 是由氟哌啶醇（HP）掺入聚亚乙基亚胺-聚组氨酸（PP）胶束构建而成，进一步与低分子量肝素（LMWH）-氯己定（Ce6）缀合物（LC）结合形成 HP@PP/LC 纳米颗粒（NPs）。对于 HP@PP/LC NPs，在肿瘤组织中 PP 的质子化精确靶向 BCSCs，通过促进 BCSCs 分化为肿瘤细胞来重塑失衡状态。同时，LC 缀合物靶向肿瘤，通过 LMWH 发挥 EMT 阻断能力，并通过 Ce6 成分发挥光动力清除肿瘤细胞的能力。因此，我们的纳米平台为操纵 BCSCs 以对抗肿瘤的进展和转移提供了一种新兴策略，展示了一种有前途的针对肿瘤的光动力平台。
