Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody

TLDR

Melanoma treatment with anti‑PD‑1 immunotherapy has advanced, yet its efficacy still needs improvement. The study introduces a self‑degradable microneedle patch for sustained, physiologically controllable delivery of anti‑PD‑1. The patch employs hyaluronic‑acid microneedles loaded with pH‑sensitive dextran nanoparticles containing aPD1 and glucose oxidase; glucose‑derived acid triggers nanoparticle dissociation and releases aPD1. A single MN patch dose elicits stronger immune responses than non‑degradable MN or free aPD1 injection in B16F10 mice, and the approach synergizes with other immunomodulators such as anti‑CTLA‑4 to boost antitumor efficacy.

Abstract

Despite recent advances in melanoma treatment through the use of anti-PD-1 (aPD1) immunotherapy, the efficacy of this method remains to be improved. Here we report an innovative self-degradable microneedle (MN) patch for the sustained delivery of aPD1 in a physiologically controllable manner. The microneedle is composed of biocompatible hyaluronic acid integrated with pH-sensitive dextran nanoparticles (NPs) that encapsulate aPD1 and glucose oxidase (GOx), which converts blood glucose to gluconic acid. The generation of acidic environment promotes the self-dissociation of NPs and subsequently results in the substantial release of aPD1. We find that a single administration of the MN patch induces robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. Moreover, this administration strategy can integrate with other immunomodulators (such as anti-CTLA-4) to achieve combination therapy for enhancing antitumor efficacy.