Aniview Support Tumor Theranostics Research: A ternary heterostructured nanocrystal featuring an S-scheme heterojunction for enhanced penetration and ROS-amplified tumor ablation

New progress has been made in multifunctional nanocatalytic tumor theranostics.

Professor Xilong Wu’s team from Hainan University published their findings in “ Advanced Functional Materials” (IF = 19.0, top-tier journal).

This study provides new insights into Photo-/acoustic-/magnetic-responsive nanoplatforms for enhancing ROS-mediated tumor therapy, achieving efficient deep tumor ablation, and activating antitumor immune responses.

Reactive oxygen species (ROS)-based tumor ablation therapy has become a highly promising tumor treatment strategy because it can induce oxidative damage, apoptosis, and immunogenic cell death (ICD) in tumor cells, while exhibiting relatively low systemic toxicity. Among these approaches, photodynamic therapy (PDT) and sonodynamic therapy have attracted much attention due to their advantages of spatiotemporal controllability and minimal invasiveness. However, these therapies have significant limitations. PDT relies on visible light excitation, which has poor tissue penetration, and its efficacy is restricted by the hypoxic tumor microenvironment. Traditional sonodynamic therapy (SDT) also depends on oxygen and is susceptible to ROS scavenging by high concentrations of glutathione (GSH) in the tumor microenvironment. Although ultrasound piezoelectric catalytic therapy (UPCT) can generate ROS under hypoxic conditions, it still faces the problem of insufficient catalytic efficiency. Meanwhile, conventional heterojunctions such as Type-II and Z-scheme structures either sacrifice redox potential or suffer from structural complexity and low efficiency. Although S-scheme heterojunctions can retain strong redox carriers and improve charge separation efficiency, they are rarely applied in integrated tumor theranostics. In addition, tumor accumulation and deep penetration of nanomedicines rely on the enhanced permeability and retention (EPR) effect, which is difficult to overcome due to abnormal tumor vasculature, high interstitial fluid pressure, and dense extracellular matrix barriers. Although magnetic fields and ultrasound can assist nanoparticle penetration, nanoplatforms that integrate photo-/acoustic-/magnetic-responsiveness with synergistic multimodal catalytic therapy and imaging guidance are still extremely scarce. These issues collectively make it difficult for ROS-mediated tumor therapy to achieve efficient, deep, and precise ablation.

In this study, a photo-/acoustic-/magnetic-responsive ternary heterostructured nanocrystal BPNS/PCN-224/Fe₃O₄ @PVP (BPF) was successfully constructed. Through the synergistic effects of an internal S-scheme heterojunction and iron-based nanozyme catalysis, it effectively overcomes the core bottlenecks of traditional ROS-based tumor therapies. In this nanoplatform, the S-scheme heterojunction formed by BPNS and PCN-224 significantly promotes charge separation under light and ultrasound excitation, suppresses electron–hole recombination, and greatly enhances ROS generation efficiency, enabling highly efficient synergy between photodynamic therapy and ultrasound piezoelectric catalytic therapy. The superparamagnetic Fe₃O₄ nanoparticles possess both peroxidase-like and catalase-like activities, which can catalyze H₂O₂ to generate hydroxyl radicals to enhance chemodynamic therapy, as well as decompose endogenous H₂O₂ to produce oxygen to alleviate tumor hypoxia, while consuming GSH to reduce ROS scavenging and further amplify oxidative stress. Under the combined driving of ultrasound and a magnetic field, BPF can efficiently accumulate and actively penetrate deep into tumors, improving its intratumoral distribution. Meanwhile, based on PCN-224 and Fe₃O₄ , it enables dual-modal imaging of near-infrared fluorescence and T₂-weighted magnetic resonance imaging, providing real-time guidance for therapy. Both in vitro and in vivo experiments confirmed that BPF-mediated multimodal synergistic therapy can efficiently kill tumor cells, induce immunogenic cell death, and activate systemic antitumor immune responses and immune memory. It not only significantly inhibits primary tumor growth but also effectively prevents tumor recurrence and lung metastasis. In addition, this nanomaterial exhibits good biocompatibility and in vivo safety, providing a new strategy for ROS-amplified tumor ablation therapy for deep tumors that integrates diagnosis and treatment with immune activation.

Experiments using Aniview

In this study, the AniView Phoenix full-spectrum in vivo imaging system from Guangzhou Biolight Biotechnology Co., Ltd. was used to observe the distribution, tumor-targeted accumulation, and metabolic clearance of BPF in mice. The results showed that BPF could efficiently accumulate at tumor sites through the EPR effect combined with magnetic targeting, reaching peak fluorescence intensity at 6 hours and then being gradually metabolized and cleared over time. The application of an external magnetic field significantly enhanced its accumulation and retention in tumor tissues. In addition, the material was mainly metabolized through the liver and kidneys, and the fluorescence signal at tumor sites was significantly higher than that in normal organs, demonstrating excellent tumor-targeting capability and good biosafety.

DOI：10.1002/adfm.75094