Microneedle-Based Nanomotor Cancer Vaccine Combined with Chemotherapy for Synergistic Melanoma Therapy

Abstract

The combination of cancer vaccines and chemotherapy represents a promising therapeutic strategy for tumor treatment. However, the commonly used intravenous injection method often results in limited therapeutic efficacy. To address this challenge, we develop a therapeutic nanomotor cancer vaccine capable of activating immune responses and employ microneedle technology to achieve efficient co-delivery of the nanomotor cancer vaccine and the chemotherapeutic drug doxorubicin (DOX). The nanomotor cancer vaccine is prepared using the desolvation method, with its primary components including the cancer vaccine formed by self-assembly of bovine serum albumin (BSA) and the antigen ovalbumin (OVA), as well as L-arginine (LA) loaded via physical adsorption. These components are co-encapsulated into hyaluronic acid-based microneedles. Upon insertion into the skin, the hyaluronic acid matrix rapidly dissolves, releasing the nanomotor cancer vaccine (OVA/BSA-LA). The LA component enables the nanomotor to specifically target tumor tissues by binding to the highly expressed inducible nitric oxide synthase (iNOS), achieving chemotactic tumor targeting. The nitric oxide (NO) generated during this process induces immunogenic cell death in tumor cells, while the antigen OVA promotes immune cell maturation, activates T cell differentiation, and triggers antitumor immune responses. When combined with DOX, the therapeutic efficacy is further enhanced. In vitro and in vivo experiments demonstrate that the microneedle-based nanomotor cancer vaccine, in combination with chemotherapy, exhibits good efficacy in treating melanoma, offering a promising strategy for melanoma therapy.