Multifunctional exosome-driven tumor immunotherapy sensitization: converting intratumoral bacteria into antitumor...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Intratumoral bacteria can evade immune surveillance by hiding within tumor cells.
• Reprogramming tumor-associated macrophages (TAMs) to a tumoricidal M1 phenotype is a key strategy in cancer immunotherapy.
• Developing methods to effectively deliver therapeutic agents to intratumoral bacteria and enhance macrophage activity is crucial.

Purpose of the Study:

• To develop a multifunctional exosome-based system to sensitize cancer immunotherapy by targeting intratumoral bacteria.
• To investigate the synergistic effects of ferroptosis and photothermal therapy in inducing tumor cell and bacterial death.
• To enhance macrophage phagocytosis of bacteria and subsequent polarization into M1 phenotype.

Main Methods:

• Construction of multifunctional exosomes loaded with Fe3O4 nanoparticles (ferroptosis inducer) and ICG (photothermal agent).
• Utilizing dead tumor cells as a bridge to connect TAMs with intratumoral bacteria.
• Employing CD47 blockade to enhance macrophage phagocytosis of bacteria.
• Evaluating the therapeutic efficacy through synergistic ferroptosis and photothermal therapy, immune cell polarization, and tumor suppression.

Main Results:

• The multifunctional exosomes induced synergistic ferroptosis and photothermal therapy, leading to efficient tumor cell and intratumoral bacteria death.
• Killed tumor cells exhibited enhanced immunogenicity, and combined with CD47 blockade, promoted bacterial phagocytosis by macrophages.
• Engulfed bacteria successfully polarized TAMs into the tumoricidal M1 phenotype, enhancing antitumor immunity and T cell infiltration.
• The treatment resulted in significant suppression of tumor growth and metastasis.

Conclusions:

• Multifunctional exosomes effectively convert intratumoral bacteria into antitumor fighters, sensitizing cancer immunotherapy.
• The strategy overcomes bacterial evasion and enhances macrophage-mediated antitumor responses.
• This approach holds promise for effective cancer treatment by provoking robust antitumor immunity and suppressing tumor progression.