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

Immune checkpoint blockade therapy, particularly the use of engineered monoclonal antibodies against programmed cell death protein 1 (alpha-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 alpha-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 alpha-PD1 against both primary and distant tumors. In addition, the presence of manganese ions offers strong contrast in T-1-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.

Automated summary

Researchers have successfully used core-shell metal ion-drug nanoparticles to enhance the antitumor responses of immune checkpoint blockade therapy by combining chemotherapy and photodynamic therapy, showcasing improved drug delivery and stability, as well as strong anticancer effects in tumor-bearing mice.