Immune cell targeting-mediated cytomimetic drug delivery system for BBB-penetrating and precise therapy of in situ glioma

Gliomas are a group of highly malignant tumors that are prone to recurrence after surgery. Due to the limitation of the blood-brain barrier (BBB), most antitumor drugs cannot cross it. Therefore, improving the delivery efficiency of antitumor drugs in their treatment remains a significant challenge. Herein, we report a unique cellular biomimetic drug delivery system (CTP@RAW) that benefits from the exceptional immune homing and long-term tracking ability of RAW 264.7 cells to specifically penetrate BBB and target tumor sites. The drug (TMZ) is encapsulated in RAW264.7 to avoid being cleared or degraded by the blood, improve bioavailability and reduce systemic toxicity. And that, owning to polydopamine (PDA) coating on the quantum dots-drug nanoparticles, which can endogenously and controllably release TMZ in response to certain tumor microenvironment (high GSH and low pH). This delivery system can also achieve precise localization and real-time visualization of tumors via fluorescence imaging. The released drugs effectively inhibit tumor growth by regulating cytokine expression levels, including GFAP, Ki67, Caspase-3, and TNF-α. Our study demonstrates that this drug delivery system can cross BBB, improve drug delivery efficiency, and has excellent potential for visualization and precision treatment of in situ gliomas.