# Nanoparticulated Anti-Programmed Cell Death-1 Antibody Improves Localized Immune Checkpoint Blockade Therapy

## TL;DR

Researchers developed a nanoparticle-based antibody treatment that improves localized cancer therapy by boosting immune response and reducing side effects.

## Contribution

A novel nanoformulation of anti-PD-1 antibody using mesoporous polydopamine nanoparticles enhances immune checkpoint blockade therapy.

## Key findings

- The nanoformulation increased antagonistic activity of aPD-1 against PD-1 receptors, blocking immune checkpoint signaling.
- Local intratumoral injection of the nanoformulation enhanced tumor retention and antitumor efficacy.
- Nano-ICI treatment effectively orchestrated antitumor immunity for both local and systemic cancer treatment.

## Abstract

Immune checkpoint inhibitors (ICIs) have successfully transformed clinical oncology against various cancers. However, their widespread utility is limited by low response rates and severe adverse events; thus, a safe and effective approach is required to address these issues. Here, we report the nanoengineering of an anti-programmed cell death-1 antibody (aPD-1) to boost the therapeutic effects following direct local administration into tumors. Specifically, we prepared an aPD-1 nanoformulation using biocompatible mesoporous polydopamine nanoparticles (MPNs) that allow facile and efficient surface functionalization of aPD-1 via latent reactivity to proteins. The nanoformulation increased the antagonistic activity of aPD-1 against PD-1 receptors by enhancing their avidity interactions, effectively blocking PD-1 immune checkpoint signaling in T cells to restore their activation and effector function. The nanoformulation administered via local intratumoral injection enhanced tumor retention of aPD-1 and elicited strong antitumor efficacy against local tumors and long-term tumor recurrence. Our results indicate that robust immune checkpoint signaling blockade in the local tumors using nano-ICI treatment can effectively orchestrate antitumor immunity for local and systemic cancer treatment. Overall, this study underscores the potential of a biomaterial-based nanoengineering approach for improving the efficacy and safety of antibody-based ICI therapy with localized tumor treatment.