Self-delivery immunological adenosine effector for photodynamic activated immunotherapy against metastatic tumors

Abstract

Therapy-induced immunogenic cell death (ICD) can trigger a burst release of immunostimulatory signals, but some of them can be converted into immunosuppressive factors to extensively restrict systemic anti-tumor immunity. In this work, a self-delivery immune adenosine effector (designated as iMade) is fabricated to eliminate metastatic tumors via photodynamic activated immunotherapy. Among which, nano-sized iMade is composed of pyropheophorbide-a (Pyro) and imaradenant (AZD) through drug self-assembly without extra excipients. Interestingly, the uniform iMade exhibits favorable stability and dispersity, helping improve the drug delivery efficiency in tumor tissues and cells. Mechanistically, the photodynamic therapy (PDT) of iMade can not only inhibit tumor cell proliferation, but also act as an ICD trigger to induce the burst release of danger related molecular patterns (DAMPs). Successively, AZD is released from iMade to reduce the recognition of adenosine and A2AR for enhanced antigen presentation. Ultimately, iMade is demonstrated to efficiently suppress the growth of primary tumor in vivo, and simultaneously activate systemic immune response to reduce metastatic tumors while cause no obvious systemic side effects. Such a simple but efficient strategy might provide a promising combinatory for spatiotemporal tumor treatment.

Keywords

• Self-delivery nanomedicine
• Immunogenic cell death
• Adenosine receptor
• Photodynamic therapy
• Immunotherapy