Abstract
1038
Introduction: Gold nanostar (AuNS) displays a high photothermal conversion efficiency and has been applied for in vitro and in vivo photothermal therapy (PTT) of various tumors. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) provide a powerful tool for in vivo tracking of nanoparticles. In this study, we synthesized PEGylated AuNS (pAuNS) and its radioactive surrogate to evaluate its biological characteristics. The results of biodistribution and SPECT images may be adopted in designing the procedure of cancer treatment. The potential of pAuNS-mediated PTT was evaluated in a SKOV-3 human ovarian tumor-bearing mouse model.
Methods: AuNS with a maximal plasma absorption peak at ~790 nm and an average size of 46.8±3.6 nm was synthesized by HEPES-reduction method, and then PEGylated to obtain pAuNS. The temperature rise of pAuNS in different buffers after 793 nm near infrared (NIR) laser irradiation was recorded with a thermal camera. DTPA-conjugated pAuNS was labeled with indium-111 to obtain 111In-DTPA-pAuNS with high radiolabeling efficiency (94.8±1.4%) and good in vitro stability (>95% after 72 h of incubation in serum). The biological characterizations of 111In-DTPA-pAuNS were conducted in mice bearing SKOV-3 human ovarian xenografts. The tumor gold concentration was estimated based on the results of biodistribution and validated by the inductively coupled plasma mass spectrometry (ICP-MS). The anti-tumor effect of pAuNS-mediated PTT was also evaluated in the same animal tumor model.
Results: The heat generation after NIR irradiation (1.0 and 1.5 W/cm2) of pAuNS-containing normal saline and fetal bovine serum increased in a dose-dependent manner. MicroSPECT/CT images revealed that most of 111In-DTPA-pAuNS after intravenous injection retained in liver and spleen in the tumor-bearing mice. The gold content in tumor determined by 111In-radioactivity and ICP-MS was considerably correlated (R2 >0.7), indicated that 111In-DTPA-pAuNS is a suitable radioactive surrogate of pAuNS. At 24 h post-injection of 111In-DTPA-pAuNS, the tumor-to-muscle ratio reached plateau and was selected as the time point for pAuNS-mediated PTT. Comparing to NIR irradiation only, the tumor temperature rise was more remarkable, accompanied with a significantly inhibited tumor growth, in pAuNS-mediated PTT treatment group. No pathological changes or injuries were detected in main organs following pAuNS administration.
Conclusions: We demonstrated the anti-tumor effect of pAuNS-mediated PTT in treating ovarian cancer. 111In-labeled pAuNS (i.e. 111In-DTPA-pAuNS) was successfully synthesized and used for investigating the biological behaviors of pAuNS, which hence facilitated the selection of the appropriate time point for pAuNS-mediated PTT.