Liposomal nanohybrid cerasomes targeted to PD-L1 enable dual-modality imaging and improve antitumor treatments.

Abstract

Programmed death ligand-1 (PD-L1) is a central element in cancer therapies targeting immune checkpoints, and its expression is an important predictor of the therapeutic response. With recent approvals of therapeutic antibodies against PD-L1 and PD-1, noninvasive detection methods are now urgently needed to quantify PD-L1 expression in tumors and to evaluate the response to immune therapies. However, only few such methods are available. Thus, we fabricated nanohybrid liposomal cerasome nanoparticles loaded with the chemotherapeutic drug paclitaxel, and evaluated their value as a theranostic agent. The particles are also decorated with PD-L1 antibody to enable specific targeting, and are dual-labeled to enable near-infrared fluorescence (NIRF) and magnetic resonance imaging (MRI) in vivo. Results showed that in vivo NIRF and MRI imaging following intravenous injection of cerasomes revealed a strong positive contrast for tumors, indicating long-lived enhancement of relevant signals. Moreover, the cerasomes were more effective against tumors and metastasis in comparison to simultaneous but nontargeted delivery of PD-L1 antibody and paclitaxel. Taken together, the data indicate that targeted, dual-labeled cerasomes are good theranostic agents for MRI/NIRF dual-mode detection and treatment of solid tumors in situ.