Stimuli-Responsive Hydrogels Potentiating Photothermal Therapy against Cancer Stem Cell-Induced Breast Cancer...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Cancer stem cells (CSCs) drive chemoresistance and recurrence in breast cancer.
• Existing CSC-targeting drugs face challenges with inefficient delivery and tumor accumulation.
• Targeting CSC self-renewal and differentiation is crucial for effective breast cancer treatment.

Purpose of the Study:

• To develop a thermoresponsive hydrogel for controlled delivery of thioridazine (THZ) to breast cancer stem cells.
• To utilize an aggregation-induced emission (AIE)-active photothermal agent for triggered drug release.
• To evaluate the efficacy of the hydrogel system in augmenting THZ-mediated CSC ablation and suppressing tumor progression.

Main Methods:

• Coencapsulation of an AIE photothermal agent and THZ within a thermoresponsive hydrogel.
• Near-infrared laser irradiation to induce hydrogel deformation and drug release.
• In situ tumor administration and evaluation of CSC apoptosis, tumor growth, recurrence, and metastasis in a mouse model.

Main Results:

• The AIE agent-triggered hydrogel system demonstrated controlled, burst release of THZ upon laser stimulation.
• In situ administration facilitated deep tumor penetration and accumulation of THZ.
• Significant CSC apoptosis, tumor growth inhibition, and suppression of recurrence and metastasis were observed in treated mice.
• The system effectively augmented THZ-mediated CSC ablation via dopamine receptor blockage and oxidative stress induction.

Conclusions:

• The developed intelligent hydrogel system offers a promising strategy for targeted delivery of THZ to combat chemoresistant breast cancer stem cells.
• This controllable drug delivery approach enhances therapeutic efficacy and reduces tumor recurrence and metastasis.
• The system holds significant clinical potential for treating metastatic breast cancer.