Reversing Resistance of Cancer Stem Cells and Enhancing Photodynamic Therapy Based on Hyaluronic Acid Nanomicelles for Preventing Cancer Recurrence and Metastasis

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, a hyaluronic acid (HA)-Ce6-Olaparib (OLA) micelle (HCCO) is developed, 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. This 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. A hyaluronic acid (HA)-Ce6-Olaparib (OLA) micelle (HCCO) is developed. HCCO induced immunogenic cell death (ICD) effects and alleviated myeloid-derived suppressor cells (MDSCs) infiltration to reverse CSC resistance. HCCO inhibits tumor recurrence and metastasis by the combination of inhibiting DNA damage repair, reversing CSC resistance, and enhancing PDT.image