1103 - A Multifunctional BSA-THPC@Tc-99m Nanoplatform for Fluorescence/SPECT Dual-Mode Imaging-Guided Synergistic Sonodynamic and Radiotherapy of Tumors

05:05pm - 05:10pm ET

Room 156

Presenter(s)

Liting Chen, - Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an,

L. Chen¹, and L. Zhao²; ¹Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, China, ²Department of Radiation Oncology, First Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi, China

Purpose/Objective(s): To develop a multifunctional nanoplatform (BSA-THPC@Tc-99m) by loading the sonosensitizer THPC into bovine serum albumin (BSA) nanoparticles and labeling with the radionuclide Tc-99m, aiming to achieve fluorescence/SPECT dual-mode imaging-guided synergistic sonodynamic therapy (SDT) and radiotherapy (RT) for enhanced antitumor efficacy.

Materials/Methods: BSA-THPC@Tc-99m nanoparticles were synthesized and characterized for hydrodynamic size, polydispersity index (PDI), surface charge, colloidal stability, hemocompatibility, and optical properties. Cellular uptake, reactive oxygen species (ROS) generation, and in vitro cytotoxicity (with and without ultrasound/X-ray irradiation) were evaluated in 4T1 breast cancer cells. In vivo dual-modal imaging (fluorescence and SPECT/CT) was performed in 4T1 tumor-bearing mice to assess tumor accumulation and biodistribution. Antitumor efficacy of combined SDT and RT was evaluated by tumor growth inhibition following intravenous injection and subsequent ultrasound/X-ray irradiation.

Results: The nanoplatform exhibited a uniform size (~15 nm, PDI<0.3), favorable surface charge (~-15 mV), excellent stability, and retained THPC optical properties (absorption/emission at ~650/660 nm). It was efficiently internalized by 4T1 cells in a concentration- and time-dependent manner, producing primarily singlet oxygen (¹O2) upon ultrasound irradiation. In vitro, the nanoparticles showed good biocompatibility, while combined ultrasound and X-ray irradiation induced significant synergistic cytotoxicity. In vivo, fluorescence and SPECT/CT imaging revealed efficient tumor accumulation via the EPR effect, peaking at ~5 h post-injection (~20 %ID/g). Combined SDT and RT at this time point achieved superior tumor growth inhibition compared to monotherapies.

Conclusion: The BSA-THPC@Tc-99m nanoplatform integrates tumor-targeted delivery, dual-modal imaging, and synergistic SDT/RT, demonstrating strong potential for image-guided combination cancer therapy.