Combining anti-PD-1 antibodies with Mn²⁺-drug coordinated multifunctional nanoparticles for enhanced cancer therapy.

Abstract

Immune checkpoint blockade therapy, particularly the use of engineered monoclonal antibodies against programmed cell death protein 1 (α-PD1) for activating T cells to kill cancer cells, becomes an effective strategy for cancer treatment. Despite its durable clinical responses, the modest response rates largely restrict the extensive implementation of this approach. Here, a combination of chemotherapy and photodynamic therapy to augment antitumor responses of α-PD1 has been achieved by core-shell metal ion-drug nanoparticles. The core and shell are separately formed by self-assembly of manganese ions with chemotherapeutic doxorubicin and photosensitizer chlorin e6, resulting in nanoparticles with drug loading up to 90 weight%. To assist systemic delivery and prolong circulation time, the obtained nanoparticles are coated with red blood cell membranes that can improve their dispersity and stability. Following intravenous injection into immunocompetent tumor-bearing mice, the coated nanoparticles initiate enhanced antitumor responses of α-PD1 against both primary and distant tumors. In addition, the presence of manganese ions offers strong contrast in T₁-weighted magnetic resonance imaging of tumors. Multimodal core-shell metal ion-drug nanoparticles suggest an alternative to boost anticancer responses and open a window for improving the response rates of immune checkpoint blockade therapy.