Spatial confinement growth of high-performance persistent luminescence nanoparticles for image-guided sonodynamic therapy

Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) have significant potential in diagnostic and therapeutic applications owing to their unique persistent luminescence (PersL). However, obtaining high-performance NIR PLNPs remains challenging because of the limitations of current synthesis methods. Herein, we introduce a spatial confinement growth strategy for synthesizing high-performance NIR PLNPs using hollow mesoporous silica (hmSiO₂). By calcining precursor ions in the hollow cavity, the yolk size of NIR PLNPs was regulated, yielding well-dispersed Zn_1.3Ga_1.4Sn_0.3O₄: Cr_0.005, Y_0.003@hmSiO₂ (ZS) with a yolk-shell structure. Compared to the conventional template method, ZS synthesized via the spatial confinement growth strategy exhibited a 7.7-fold increase in PersL intensity and a threefold increase in specific surface area. As a proof of concept, ZS@PpIX@CaP-AMD (ZPSC-AMD) nanoparticles, with potential for sonodynamic therapy (SDT), were synthesized by loading the sonosensitizer protoporphyrin IX (PpIX) into ZS, coating it with a calcium phosphate (CaP) shell, and modifying it with a tumor-targeting molecule plerixafor (AMD-3100). The tumor enrichment behavior of ZPSC-AMD was monitored by sensitive NIR PersL to guide SDT. Simultaneously, ZPSC-AMD enabled the precise monitoring of tumor accumulation, thereby guiding effective SDT. In addition, Ca²⁺ released from CaP degradation increased the level of reactive oxygen species during SDT, promoting tumor cell apoptosis. This study outlines a reliable design and synthesis approach for high-performance NIR PLNPs and promotes their development in biomedical applications.

Statement of Significance

The potential of near infrared (NIR) persistent luminescence nanoparticles (PLNPs) in bio applications is hindered by limitations in the synthesis method. In this article, we proposed a spatial confinement growth strategy of high-performance NIR PLNPs. The obtained PLNPs with yolk-shell structure showed a 7.7-fold increase in PersL intensity and a threefold increase in specific surface area, compared with the commonly used template method. Due to the advantages, sonodynamic therapeutic nanoparticles were constructed based on the above PLNPs, where persistent luminescence was used for ultrasensitive imaging to determine the optimal timing in sonodynamic therapy. In addition, the multifunctional calcium phosphate shell elevated the intracellular reactive oxygen species level to promote tumor cell apoptosis.