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Tc 标记的 HA/TPGS 载姜黄素纳米粒子用于乳腺癌协同治疗学的研究：设计、体外和体内评价。

Tc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation.

机构信息

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.

出版信息

Int J Nanomedicine. 2020 Apr 30;15:2987-2998. doi: 10.2147/IJN.S242490. eCollection 2020.

DOI:10.2147/IJN.S242490
PMID:32431497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7200226/
Abstract

BACKGROUND

Emerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)-loaded nanoparticle of Tc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics.

MATERIALS AND METHODS

The synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice.

RESULTS

HA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 μg/mL, compared with free curcumin (77 μg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with Tc. The SPECT images showed that Tc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85±0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs.

CONCLUSION

The results indicated that HA-CHEMS-Cur-TPGS NPs with stable Tc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.

摘要

背景

新兴的癌症治疗需要高度敏感的诊断，结合癌症靶向治疗。在这项研究中，一种自组装的 pH 敏感姜黄素（Cur）负载的纳米粒子由放射性标记的透明质酸-胆固醇琥珀酸酯缀合物（HA-CHEMS）和 D-a-生育酚聚乙二醇琥珀酸酯（TPGS）组成，用于乳腺癌协同治疗。

材料和方法

合成的两亲性 HA-CHEMS 缀合物和 TPGS 在水相环境中自组装成 Cur 负载的纳米粒子（HA-CHEMS-Cur-TPGS NPs）。通过透射电子显微镜（TEM）和动态光散射（DLS）对 HA-CHEMS-Cur-TPGS NPs 的物理化学性质进行了表征。采用噻唑蓝（MTT）法评价 HA-CHEMS-Cur-TPGS NPs 对乳腺癌细胞的体外细胞毒性。此外，在 4T1 荷瘤 BALB/c 小鼠中进行了 HA-CHEMS-Cur-TPGS NPs 的体内动物实验，包括 SPECT/CT 成像生物分布和抗肿瘤效率，并在健康小鼠中进行了药代动力学研究。

结果

HA-CHEMS-Cur-TPGS NPs 表现出高姜黄素载量、均匀的粒径分布和体外优异的稳定性。在细胞毒性试验中，HA-CHEMS-Cur-TPGS NPs 对 4T1 细胞表现出明显更高的细胞毒性，IC50 值为 38μg/mL，而游离姜黄素为 77μg/mL。此外，HA-CHEMS-Cur-TPGS NPs 可以有效地稳定地放射性标记 Tc。SPECT 图像显示，Tc-HA-CHEMS-Cur-TPGS NPs 在注射后 4 小时在 BALB/c 小鼠中可达到 4.85±0.24%ID/g 的 4T1 肿瘤靶标。更重要的是，体内抗肿瘤疗效研究表明，HA-CHEMS-Cur-TPGS NPs 能显著抑制肿瘤生长，而对主要器官无明显毒性。

结论

结果表明，具有稳定 Tc 标记和高姜黄素载量的 HA-CHEMS-Cur-TPGS NPs 具有用于乳腺癌协同治疗的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bb0/7200226/8e96e5c8d3e1/IJN-15-2987-g0007.jpg
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