Classical Monocytes Shuttling for Precise Delivery of Nanotherapeutics to Glioblastoma.

Glioblastoma (GBM) is the most aggressive brain tumor for which current therapies have limited efficacy. Immunosuppression and difficulties in accessing tumors with therapeutic agents are major obstacles for GBM treatments. Classical monocytes (CMs) possess the strongest infiltration among myeloid cells recruited into tumors during tumorigenesis. In this study, CMs are utilized to deliver the small-molecule CUDC-907 encapsulated in nanoparticles (907-NPs@CMs) for GBM therapy. Hitchhiking on CMs enables more 907-NPs to successfully penetrate the blood-brain barrier (BBB) and reach the interior of tumors. Results demonstrate that 907-NPs@CMs significantly improve the survival rates by suppressing tumor growth and reversing the immunosuppression of tumor microenvironment (TME). Furthermore, the high delivery efficiency of CMs reduces the amount of CUDC-907 required for treatments, reducing the physiological toxicity and off-target effects caused by high doses. 907-NPs@CMs is a safe and versatile therapeutic system that provides a platform for targeted drug delivery to tumors and the ability to treat GBM through a combination of chemotherapy and immunotherapy.