Lin Ssu-Yu, Huang Rih-Yang, Liao Wei-Chen, Chuang Chun-Chiao, Chang Chien-Wen
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan R.O.C.
Nanotheranostics. 2018 Jan 1;2(2):106-116. doi: 10.7150/ntno.19379. eCollection 2018.
A multifunctional albumin/superparamagnetic iron oxide nanoparticle (SPIO) nanocomplex system to deliver IR780, a photothermal agent, for cancer theranostic applications was proposed in this study. Single emulsion method was utilized to fabricate the human albumin/IR780/SPIO (HISP) nanocomplexes with a hydrophobic core (SPIO and IR780) and a hydrophilic shell (human serum albumin (HSA) and poly (ethylene glycol) (PEG)). Effects of PEGylation on the size and surface potential of nanocomplexes were analyzed. Nanospheres containing uniformly dispersed SPIO was observed using Transmission Electron Microscopy (TEM) imaging. As a potential magnetic resonance (MR) imaging agent, the HISP displayed dose-dependent T2-weighted imaging contrast (R2 = 81.6 mMs). Good colloidal stability was verified from the nanocomplexes under difference circumstances. The nanocomplexes were taken up by cancer cells efficiently and led to significant photothermal-mediated cancer cell death upon short-term near infrared (NIR) irradiation . intravenous injection, PEG-HISP can efficiently deliver IR780 to tumor sites and showed strong photothermal effect compared to free drug on the mice model. Significant tumor suppression by the photothermal treatments using PEG-HISP was demonstrated from the mice CT26 xenograft model. Good safety profile of the PEG-HISP was confirmed from histological examination and liver functional analysis. Taken together, the results suggest that PEG-HISP is a safe and robust nano-theranostic platform for advanced anti-cancer treatment.
本研究提出了一种多功能白蛋白/超顺磁性氧化铁纳米颗粒(SPIO)纳米复合系统,用于递送光热剂IR780,以应用于癌症诊疗。采用单乳液法制备了具有疏水核心(SPIO和IR780)和亲水外壳(人血清白蛋白(HSA)和聚乙二醇(PEG))的人白蛋白/IR780/SPIO(HISP)纳米复合物。分析了聚乙二醇化对纳米复合物尺寸和表面电位的影响。使用透射电子显微镜(TEM)成像观察到含有均匀分散SPIO的纳米球。作为一种潜在的磁共振(MR)成像剂,HISP表现出剂量依赖性的T2加权成像对比度(R2 = 81.6 mMs)。在不同情况下验证了纳米复合物具有良好的胶体稳定性。纳米复合物被癌细胞有效摄取,并在短期近红外(NIR)照射后导致显著的光热介导的癌细胞死亡。静脉注射后,与游离药物相比,PEG-HISP可以有效地将IR780递送至肿瘤部位,并在小鼠模型上显示出强烈的光热效应。从小鼠CT26异种移植模型中证明了使用PEG-HISP进行光热治疗可显著抑制肿瘤。通过组织学检查和肝功能分析证实了PEG-HISP具有良好的安全性。综上所述,结果表明PEG-HISP是一种用于先进抗癌治疗的安全且强大的纳米诊疗平台。