分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Liu, Renfa
Dai, Zhifei
Shi, Jiyun
Fan, Di
Wang, Fan
Shi, Jiyun
Wang, Fan
Li, Yaqian
Tian, Jie
Jing, Lijia
摘要： This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanol-amine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG(2000)-DOTA), followed by chelating radioisotope of Lu-177. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide Lu-177, enabling the ability of the Lu-177-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.
分类： 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间： 2017-05-02
Du, Y [Du, Yang][ 1 ]
Ren, WZ [Ren, Wenzhi][ 2,3 ]
Li, YQ [Li, Yaqian][ 1,4 ]
Zhang, Q [Zhang, Qian][ 1 ]
Zeng, LY [Zeng, Leyong][ 2,3 ]
Chi, CW [Chi, Chongwei][ 1 ]
Wu, AG [Wu, Aiguo][ 2,3 ]
Tian, J [Tian, Jie][ 1 ]
摘要： Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and have high levels of systemic toxicity. One of the most prominent progresses in improving drug delivery efficiency is through exploring various types of nanoparticles (NPs) as drug carriers. Recent studies have demonstrated that titanium dioxide (TiO2) nanocarriers have potential for drug delivery and therapy even in multidrug resistant cancers in vitro. Moreover, it was proved that the anticancer activity of doxorubicin (DOX) was enhanced by loading onto TiO2 nanoparticles in breast cancer cells in vitro. However, there is no evidence from the animal model in vivo, which is a critical step for their further clinical applications. The aim of this study was to explore novel TiO2–PEG–DOX nanoparticles, the DOX loaded polyethylene glycol (PEG) coated TiO2 nanocarriers, and investigate their potential application in enabling controlled drug release and enhancing the chemotherapeutic efficacy of DOX in the orthotopic breast tumor bearing mice. The tumor growth and drug treatment efficacy were dynamically monitored by bioluminescence imaging (BLI), and the safety of NPs for in vivo usage was also evaluated. It was found that TiO2–PEG–DOX nanoparticles possessed improved antitumor efficacy without observable side effects compared to the free DOX treatment. Our study suggested that the PEG coated TiO2 nanocarrier is a safe and potential platform for the efficient drug delivery and minimizing the systemic toxicity of chemotherapeutic agents. It has been proved for the first time that TiO2-based nanocarriers enhance the chemotherapeutic effects of doxorubicin in vivo.
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