Enhanced pH-Responsive Chemo/Chemodynamic Synergistic Cancer Therapy Based on In Situ Cu²⁺ Di-Chelation

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Chemodynamic therapy and chemotherapy show promise for cancer treatment.
• Developing stimulus-responsive nanoplatforms for enhanced synergistic therapy is crucial.

Purpose of the Study:

• To design a pH-responsive nanoplatform for enhanced chemo/chemodynamic synergistic cancer therapy.
• To investigate the in situ Cu2+ di-chelation strategy for improved therapeutic efficacy.

Main Methods:

• PEGylated mesoporous CuO nanoparticles (PEG-CuO@DSF@MTO NPs) were synthesized, encapsulating disulfiram (DSF) and mitoxantrone (MTO).
• The nanoparticles were designed to release Cu2+, DSF, and MTO in the acidic tumor microenvironment (TME).
• In vivo mouse models were used to evaluate the synergistic therapeutic effects.

Main Results:

• The acidic TME induced nanoparticle collapse and release of active components (Cu2+, DSF, MTO).
• In situ complexation of Cu2+ with DSF and MTO significantly enhanced chemotherapy and initiated chemodynamic therapy.
• Remarkable tumor elimination was observed in the in vivo mouse model.

Conclusions:

• The developed intelligent nanosystem demonstrates effective chemo/chemodynamic synergistic therapy.
• This strategy offers a promising approach for designing advanced cancer nanotherapeutics with potential for clinical translation.