Development of a Multifunctional BSA-Thpc@99mTc Nanoplatform for Dual-Modal Imaging-Guided Synergistic Sonodynamic and Radiotherapy
Abstract
Purpose
In this study, a novel composite nanoplatform, BSA-THPC@99mTc, was engineered by encapsulating the sonosensitizer meso-tetra (hydroxyphenyl) chlorin (THPC) into bovine serum albumin (BSA) nanoparticles, followed by radiolabeling with technetium-99m (99mTc). This platform aims to achieve synergistic antitumor efficacy through combined sonodynamic therapy (SDT) and radiotherapy (RT), guided by dual-modal fluorescence and single-photon emission computed tomography (SPECT) imaging.
Methods
The resulting nanoplatform exhibited favorable physicochemical properties, featuring a hydrodynamic diameter of approximately 15 nm with a narrow size distribution (PDI < 0.3) and a surface potential of -15 mV. BSA-THPC@99mTc demonstrated excellent colloidal stability and hemocompatibility in water, PBS, and serum-containing media. Spectroscopic analysis confirmed that the encapsulation process preserved the near-infrared (NIR) optical properties of THPC (λabs/λem≈650/660nm), ensuring its suitability for deep-tissue imaging.
Results
In vitro experiments revealed that the nanoparticles were efficiently internalized by 4T1 mammary carcinoma cells in a concentration- and time-dependent manner. Reactive oxygen species (ROS) assays validated that the system primarily generates singlet oxygen (1O2) upon ultrasound irradiation. While MTT assays confirmed the high biocompatibility of the nanoplatform alone, significant cytotoxicity was observed under ultrasound and X-ray irradiation, with the combined treatment showing a pronounced synergistic sensitization effect. In 4T1 tumor-bearing mice, both in vivo fluorescence and SPECT/CT imaging demonstrated efficient tumor accumulation of the nanoparticles via the enhanced permeability and retention (EPR) effect, peaking at 20 %ID/g approximately 5 hours post-injection. Ex vivo biodistribution further corroborated its superior tumor-targeting capability with a high tumor-to-normal organ signal ratio. Consequently, synergistic SDT/RT administered 5 hours post-injection yielded optimal therapeutic outcomes, achieving a tumor inhibition rate significantly higher than that of any monotherapy.
Conclusion
In summary, the multifunctional BSA-THPC@99mTc nanoplatform successfully integrates tumor-targeted delivery, dual-modal imaging, and synergistic SDT/RT, presenting a promising strategy for precision oncology under multimodal imaging guidance.