Hollow gold–platinum nanoshells as a delivery platform for Ce6: cascading catalysis for enhanced multimodal therapy in tumor ablation and antitumor immunity

Abstract

Precious metal nanozymes are renowned for their enzyme-mimicking properties, which can modulate the tumor microenvironment (TME) and enhance treatment. However, their small size often leads to aggregation and their single and limited catalytic potential impedes antitumor and immune-activating capabilities. To address these limitations, we developed a nanocomposite with multiple enzyme activities that synergistically enhances photodynamic and photothermal therapy (PDT and PTT), significantly boosting antitumor efficacy and immune response. Our approach involved using UiO-66-NH₂ to facilitate the growth of gold–platinum bimetallic nanozymes, resulting in a core–shell structure of UiO-66-NH₂@AuPt (UAuPt). The UiO-66-NH₂ was then etched to create hollow gold–platinum bimetallic (HAuPt) nanoshells and further encapsulated with PEG-SH and the photosensitizer Ce6 to form the HAuPt@Ce6-PEG-SH (HCP) nanocomposite. Regarding the HCP nanocomposite, its absorption capability in the near-infrared second (NIR-II) region makes it a suitable photothermal agent for PTT, while Ce6 serves as the active agent for PDT. Furthermore, the gold nanoparticles (Au NPs) and platinum nanoparticles (Pt NPs) exhibit glucose oxidase (GOD)-, catalase (CAT)-, and peroxidase (POD)-like activities. This triple-enzyme activity forms an efficient cascade catalytic system, leading to refined remodeling of the TME and efficient enhancement of PTT and PDT. Moreover, the combination therapy triggers tumor-associated macrophage (TAM) polarization and immunogenic cell death (ICD), which not only promotes dendritic cell (DC) maturation but also stimulates T cell activation and the release of tumor-specific immune factors. This cascade ultimately results in a robust antitumor immune response. The in vitro and in vivo results demonstrated a significant antitumor efficacy and immune response, promising efficient nanozymes for therapeutic advancement.