Immune checkpoint inhibitors (ICIs) have significantly advanced cancer therapy, yet their broader application is limited by low response rates and severe side effects. To overcome these challenges, we developed a nanoengineered formulation of anti-PD-1 antibody (aPD-1) designed for direct intratumoral administration. We utilized biocompatible mesoporous polydopamine nanoparticles (MPNs) to efficiently and stably functionalize aPD-1. The nano formulation enhanced aPD-1 antagonistic activity by increasing its binding avidity to PD-1 receptors, effectively inhibiting immune checkpoint signaling in T cells, restoring their activation and cytotoxic functions. Intratumoral injection improved tumor retention of aPD-1, resulting in significant antitumor effects and preventing long-term recurrence. Our findings demonstrate that localized delivery of nanoengineered ICIs effectively induces robust antitumor immunity, providing a promising strategy for safer and more effective cancer treatments.