Preparation of sinoporphyrin sodium and IR780-based composite nanoparticles and its anti-tumor efficacy in sonodynamic therapy

Objective To prepare the tumor targeting multifunctional composite nanoparticles (DIPP-NPs) by encapsulating sinoporphyrin sodium (DVDMS), IR780 and perfluorinated hexane (PFH), evaluate their physicochemical properties, and explore the synergistic enhancement of sonodynamic therapy (SDT) between DVDMS and IR780. Objective DIPP-NPs were synthesized via double emulsion and then characterized. The changes of nanoparticles before and after ultrasonic irradiation were observed by optical microscopy. Ultrasonic and photoacoustic imaging systems were used to evaluate the imaging capability in vitro. Targeting ability in vitro was evaluated by confocal laser scanning microscopy. The production of reactive oxygen species (ROS) was demonstrated by singlet oxygen detection (SOSG). CCK-8 assay was used to detect the cytotoxicity and synergistic enhancement of SDT in murine mammary carcinoma cell line 4T1. The synergistic enhancement of SDT in 4T1 xenograft mouse model was evaluated by measuring tumor volume and weight to calculate the inhibitory rates. Results DIPP-NPs were successfully prepared, as uniform round-shaped particles, 341.17±16.97 nm in diameter and -12.77±0.88 mV in Zeta potential. The encapsulation rate of DVDMS and IR780 was (92.84±1.58) % and (96.57±1.48) %, respectively. After irradiated with ultrasonic, DIPP-NPs were getting bigger and bigger in diameter under a optical microscope. Meanwhile, ultrasound imaging results showed that the ultrasound signals were enhanced with prolonged irradiation time. In addition, photoacoustic imaging results showed that the photoacoustic signal intensity was increased with the increment of nanoparticle concentration. Laser confocal microscopy demonstrated that there were more nanoparticles around 4T1 cells in DPP-NPs, IPP-NPs and DIPP-NPs groups than in PP-NPs group. SOSG detection results showed that the production of ROS was gradually increased with prolonged irradiation time. CCK-8 assay indicated that there was no obvious cytotoxicity of the nanoparticles and the cell viability in DIPP-NPS+US group was (56.04±2.28)%, which was obviously lower than that in DPP-NPS+US [(76.83±1.52)%] and IPP-NPS +US groups [(74.03±2.64)%, both P < 0.05]. Xenograft experiment showed that the inhibitory rate was (73.28±.58)% for tumor volume, and (75.76±3.49)% in weight in DIPP-NPS+US group, which were significantly higher than those in DPP-NPS+US [(46.93±4.41)%, (43.50±2.27)%] and the IPP-NPS+US groups [(47.44±1.27)%, (44.87±4.30)%, P < 0.05]. Conclusion The tumor-targeting multifunctional composite nanoparticles DIPP-NPs are successfully prepared, which have a good synergistic enhancement of SDT effectiveness.