A Novel CaCu-Metal-Organic-Framework Based Multimodal Treatment Platform for Enhanced Synergistic Therapy of...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Metal ions show promise in antitumor therapy via unique mechanisms.
• Designing metal-based multimodal treatment platforms for synergistic antitumor effects remains challenging.

Purpose of the Study:

• To develop a novel, glutathione-activatable, metal-organic framework (MOF) loaded with doxorubicin and ovalbumin for targeted synergistic cancer therapy.
• To create a multimodal treatment platform for enhanced antitumor efficacy.

Main Methods:

• Synthesis of CaCu-based MOFs loaded with doxorubicin (DOX) and ovalbumin (OVA), modified with galactosamine-linked hyaluronic acid (HG) to form SCC/DOX@OVA-HG.
• Utilized glutathione-triggered degradation for cargo release in the tumor microenvironment.
• Investigated multimodal therapeutic strategies including chemodynamic therapy (CDT), calcium overload, immunotherapy, and chemotherapy.

Main Results:

• SCC/DOX@OVA-HG demonstrated glutathione-triggered release of Cu+ and Ca2+ in the tumor microenvironment.
• Cu+ catalyzed H2O2 to generate reactive oxygen species (ROS) for CDT.
• Ca2+ induced calcium overload, enhancing metal-related cell death.
• OVA and metal ions promoted M1-like macrophage activation for immunotherapy.
• DOX facilitated chemotherapy via DNA intercalation.
• The platform achieved significant synergistic antitumor efficacy.

Conclusions:

• The developed SCC/DOX@OVA-HG platform effectively integrates chemotherapy, chemodynamic therapy, calcium overload, and immunotherapy.
• This multimodal approach significantly enhances antitumor efficacy through synergistic mechanisms.
• The targeted delivery and stimuli-responsive release contribute to improved therapeutic outcomes.