Sequentially sustained release of anticarcinogens for postsurgical chemoimmunotherapy.

Area of Science:

• Biomedical Engineering
• Cancer Immunotherapy
• Drug Delivery Systems

Background:

• Postsurgical treatment is crucial for preventing tumor recurrence and metastasis.
• The CD47-signal regulatory protein-alpha (CD47-SIRPα) pathway plays a role in immune evasion by tumors.
• Restoring immune function post-surgery can enhance anti-tumor responses.

Purpose of the Study:

• To develop an in-situ gel for chemoimmunotherapy combining chemotherapy and anti-CD47 antibodies.
• To achieve sequential drug release for optimized therapeutic effects.
• To evaluate the efficacy of the chemoimmunotherapy in preventing tumor recurrence and metastasis.

Main Methods:

• Engineered an in-situ gel by crosslinking chitosan (CS) and pullulan (Pul).
• Co-loaded liposomal cyclopamine (Cyc-Lip) and anti-CD47 antibodies (aCD47) into the gel.
• Investigated sequential drug release kinetics: burst release of Cyc-Lip followed by sustained release of aCD47.
• Assessed the chemoimmunotherapy efficacy on 4T1 mouse breast cancer models.

Main Results:

• Demonstrated sequential release of nanotherapeutics (Cyc-Lip) before aCD47.
• Cyc-Lip burst release effectively killed residual tumor cells and released tumor antigens.
• Sustained aCD47 release restored macrophage functions and enhanced anti-tumor immunity.
• The in-situ chemoimmunotherapy significantly inhibited tumor recurrence and metastasis in mouse models.

Conclusions:

• The developed in-situ gel provides a promising platform for postsurgical chemoimmunotherapy.
• Sequential drug release optimizes the killing of residual tumor cells and stimulates long-term immune memory.
• This approach effectively combats tumor recurrence and metastasis, offering a potential strategy for improved cancer patient outcomes.