Microneedles-Mediated Intradermal Delivery of Paclitaxel/Anti-PD-1 for Efficient and Safe Triple-Negative Breast Cancer Therapy

Triple-negative breast cancer (TNBC) remains one of the most fatal diseases in human populations, characterized by a high incidence and mortality rate. Although the conjunction of chemotherapeutic agents, like nanoparticle albumin-bound paclitaxel (nab-PTX), and immune checkpoint inhibitors, exemplified by the anti-PD-1 antibody (aPD-1), has surfaced as a promising modality for TNBC treatment, the optimization of their synergistic therapeutic impact while concurrently curtailing associated adverse reactions poses a persistent challenge. Here, a soluble microneedle (MN) delivery platform (designated as aPD-1/PTX NPs@MN) for the codelivery of nab-PTX and aPD-1 is developed. The soluble MN-based delivery system is anticipated to enhance the local accumulation of therapeutic agents, reducing the adverse effects associated with systemic administration. Simultaneously, heightened concentrations of glutathione within the tumor microenvironment may trigger the liberation of nab-PTX and aPD-1, inducing immunogenic cell death to promote antitumor T cells infiltration and activation by blocking the immunosuppressive PD-1 pathway, potentially culminating in a triumphant chemoimmunotherapy strategy for TNBC. A soluble microneedle delivery system is developed for the codelivery of nab-PTX and aPD-1(designated as aPD-1/PTX NPs@MNs) to exert chemotherapy and immunotherapy via a synergistic effect. aPD-1/PTX NPs@MNs enhance the local accumulation of therapeutic agents in tumor and reduce the adverse effects associated with systemic administration.image