Abstract
192
Objectives: Copper sulfide nanoparticles (CuS NPs) have emerged as one of the most promising theranostic nanoplatforms for treating cancer, due to their relatively small size, facile chemistry and excellent photothermal properties. Herein, we have designed a thermosenstive biodegradable CuS NP, which can be more clinical relevant with lower side effects. Our goal was to investigate its in vitro and in vivo biodegradation profile, and apply it to high-resolution multispectral optoacoustic tomography (MSOT) in living animals in both static and dynamic manners. Methods: Polyethylene glycol (PEG)-coated CuS NPs were synthesized via a one-step reaction with CuCl2 and Na2S as the precursors and mPEG-SH as the surfactant reacted at 90 ºC. As-prepared CuS-PEG was incubated in water/PBS in different temperatures to examine its in vitro biodegradation by transmission electron microscopy (TEM), optical absorbance based on UV-VIS-NIFR spectrometry and ion concentration based on inductively coupled plasma optical emission spectrometry (ICP-OES). CuS-PEG was injected into healthy Balb/c mice, and livers of CuS-PEG NP-injected mice were investigated over time with ICP-OES for in vivo biodegradation. MSOT was performed in SKOV-3 tumor bearing nude mice to validate the imaging capacity of the biodegradable CuS NPs.
Results: CuS-PEG NPs were successfully synthesized with superior solubility and size range 10~12 nm in diameter. After incubating with water/PBS for 7 days at 37 ºC, significant degradation (73.2 ± 0.1 %) was observed; whereas minimal degradation (14.0 ± 0.3 %) was observed when incubating at 4 ºC. Different conditions, such as air exposure and presence of residual precursors, were also investigated, suggesting that temperature is the major cause of biodegradation. Cu concentration in liver based on ICP-OES also demonstrated significant biodegradation (50.0 ± 0.4 μg NP per g tissue at 3 h p.i. v.s. 8.2 ± 0.4 μg NP per g tissue at 7 days p.i.) of CuS-PEG in vivo. Both static and dynamic MSOT showed manifestly enhanced signal in tumor after 2h p.i. which decreased with time, correlating with the in vitro findings. Of note, degraded Cu ions will not render MSOT signal, leading to more accurate imaging results in comparison to the imaging techniques that rely on radionuclides.
Conclusions: In this study, we reported a novel biodegradable CuS NPs for MSOT in living animals, which are able to effectively enhance the tumor signal and promptly degrade in several days. The degradation is controllable and temperature-dependent, making it a clinically-translatable in vivo theranostic platform with lower long-term side effects. Our study provides a comprehensive and unique perspective to evaluate CuS NPs, and may inspire future explorations into the realm of more controllable, biodegradable, and clinical relevant nanotheranostics.