Nanoparticles targeting the adenosine pathway for cancer immunotherapy.

Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.