Carbon dot-modified controllable drug delivery system for sonodynamic/chemotherapy of tumors

Tumor microenvironment-responsive drug delivery systems are essential for reducing the dosage of chemotherapy drugs and their side effects. In this study, by modifying folic acid-prepared carbon dots (CDs) and loading them with a doxorubicin (DOX) chemotherapy drug, we fabricate a poly(methacrylic acid) drug delivery system (DOX@CDs@HPMAA) that is responsive to pH and glutathione and achieves the effective treatment of tumors by combining chemotherapy and sonodynamic therapy. Under ultrasound excitation, CDs can continuously produce singlet oxygen, and the polymer can degrade and release DOX under the combined effect of a slightly acidic environment and glutathione. Polymer degradation consumes glutathione, while the generated singlet oxygen and DOX continuously treat the tumor, synergistically enhancing therapeutic efficacy. Mechanism studies show that the synergistic effect activates multiple signaling pathways that induce cell apoptosis and inhibit tumor proliferation. This study provides a practical approach for sonodynamic-enhanced controllable chemotherapy for synergistic tumor treatment.