光动力疗法（PDT）是一种很有前景的肿瘤治疗方法，然而，癌症干细胞（CSC）的治疗耐药性严重限制了其疗效并容易导致复发。在此，我们开发了一种透明质酸（HA）-Ce6-Olaparib（OLA）胶束（HCCO），它结合了HA的CSC靶向性、Ce6的PDT作用和OLA的DNA损伤修复抑制作用。更重要的是，HCCO 可诱导免疫原性细胞死亡 (ICD) 效应，促进树突状细胞成熟，并减轻骨髓源性抑制细胞 (MDSC) 浸润，从而逆转 CSC 耐药性。结果，HCCO不仅在体外显着抑制4T1乳腺癌细胞和CSC的生长，而且在体内有效抑制肿瘤复发和转移。我们的研究提供了一种通过抑制DNA损伤修复、逆转CSC抵抗和增强PDT相结合来预防肿瘤复发和转移的新策略。本文受版权保护。保留所有权利。本文受版权保护。版权所有。

Photodynamic therapy (PDT) is a promising approach for tumor treatment, however, the therapeutic resistance of cancer stem cells (CSCs) severely limits its efficacy and easily lead to recurrence. Herein, we develop a hyaluronic acid (HA)-Ce6-Olaparib (OLA) micelle (HCCO), which combines the CSC targeting of HA, the PDT effect of Ce6, and the DNA damage repair inhibition of OLA. More importantly, HCCO induces immunogenic cell death (ICD) effects, promotes dendritic cells maturation, and alleviates myeloid-derived suppressor cells (MDSCs) infiltration to reverse CSC resistance. As a result, HCCO not only significantly inhibits the growth of 4T1 breast cancer cells and CSCs in vitro, but also effectively inhibits tumor recurrence and metastasis in vivo. Our study provides a novel strategy for preventing tumor recurrence and metastasis by the combination of inhibiting DNA damage repair, reversing CSC resistance, and enhancing PDT. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.