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

Abstract

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.

Shedding Light on Chemoresistance: The Perspective of Photodynamic Therapy in Cancer Management

“…Moreover, PDT in combination with DNA repair inhibitors seems to be a promising strategy to overcome drug resistance. It has been recently reported that the combination of chlorin e6 and a DNA repair inhibitor (Olaparib) successfully prevented tumor recurrence and metastasis in vivo for 4T1 breast cancer [31].…”

“…CSCs play a significant role in tumor initiation, sustaining its growth and survival. They can also inhibit the immune response by preventing the maturation of dendritic cells [31]. Moreover, they are believed to exhibit greater resistance and possess different metabolic, genetic, and epigenetic signatures compared to non-CSCs, posing an additional challenge to overcoming resistance.…”

“…Notably, PDT treatment has been shown to downregulate the expression of CD44 and ALDH1, which are highly tumorigenic CSCs markers [47]. Another work has demonstrated that chlorin e6 combined with hyaluronic acid and a DNA repair inhibitor (Olaparib) successfully reverse CSCs resistance in 4T1 breast cancer [31].…”