Novel gold nanoparticles targeting somatostatin receptor subtype two with near-infrared light for neuroendocrine tumour therapy
Novel gold nanoparticles targeting somatostatin receptor subtype two with near-infrared light for neuroendocrine tumour therapy
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DOI：
10.1007/s12274-022-4555-4
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发表时间：
2022-07-15
期刊：
影响因子：
9.9
通讯作者：
Zhao, Hong
中科院分区：
文献类型：
--
作者：
Chen, Qichen;Li, Zilin;Zhao, Hong
神经内分泌肿瘤(NETs)是生长抑素受体2(SSTR2)阳性表达的罕见肿瘤，其治疗策略并不理想。在Net中针对SSTR2的纳米材料介导的治疗是非常有前途的。本研究首次将介孔二氧化硅包覆金纳米棒(AuNRs@mSiO(2))与靶向-SSTR2十二烷基四乙酸-酪氨酸(3)-辛酸(DOTA-Tate)结合在AuNRs@mSiO(2)@DOTA-Tate中，研究近红外光下Net的抑制作用。AuNRs@mSiO(2)@DOTA-Tate具有良好的光热转换效率。在体外，光照射下，随着AuNR@mSiO(2)@DOTA-Tate浓度的增加，细胞存活率显著下降；在成功建立的两种表达SSTR2的神经内分泌肿瘤有机物中，AuNRs@mSiO(2)@DOTA-Tate加光抑制肿瘤的效果明显优于AuNRs@mSiO(2)加光。在体内，AuNRs@mSiO(2)@DOTA-Tate在微电子发射断层扫描/计算机断层扫描(Micro-PET/CT)下证实了AuNRs@mSiO(2)@DOTA-Tate对SSTR2的靶向性和生物分布；在AuNRs@mSiO(2)@DOTA-Tate配合激光治疗组中，肿瘤表面温度迅速升高，肿瘤体积与奥曲肽组相似，但显著低于其他组。AuNRs@mSiO(2)@DOTA-Tate激光照射组小鼠体重与其他组比较差异无统计学意义。主要脏器未见明显炎性病变或细胞坏死。综上所述，我们提出了一种构建AuNRs@mSiO(2)@DOTA-Tate的可行策略，该策略具有良好的光热转换效率、靶向SSTR2的能力、显著的抗肿瘤作用和良好的生物相容性，为进一步探索AuNRs@mSiO(2)@DOTA-Tate在网络治疗中的应用奠定了基础。
Neuroendocrine tumours (NETs) are rare cancers with positive somatostatin receptor 2 (SSTR2) expression, and treatment strategies for NETs are not satisfactory. Nanomaterial-mediated therapy targeting SSTR2 in NETs is very promising. This study firstly combined mesoporous silica-coated gold nanorods (AuNRs@mSiO(2)) and targeting-SSTR2 dodecane tetraacetic acid-tyrosine(3)-octreotate (DOTA-TATE) into AuNRs@mSiO(2)@DOTA-TATE to investigate NETs inhibition under near-infrared light. AuNRs@mSiO(2)@DOTA-TATE showed good photothermal conversion efficiency. In vitro, under light irradiation, the cell viability significantly decreased with increasing AuNR@mSiO(2)@DOTA-TATE concentration; in two successfully established neuroendocrine tumour organoids with SSTR2 expression, AuNRs@mSiO(2)@DOTA-TATE with light inhibited tumours significantly better than AuNRs@mSiO(2) with light. In vivo, the SSTR2-targeting ability and biodistribution of AuNRs@mSiO(2)@DOTA-TATE were confirmed with AuNRs@mSiO(2)@Cu-64-DOTA-TATE under micro-positron emission tomography/computed tomography (micro-PET/CT); in the AuNRs@mSiO(2)@DOTA-TATE with laser group, the tumour surface temperature increased rapidly, with tumour volumes similar to those in the octreotide group and significantly lower than those in other groups. There was no significant difference in mice body weight between the AuNRs@mSiO(2)@DOTA-TATE with laser group and other groups. No significant inflammatory lesions or cell necrosis was found in the main organs. In summary, we presented a feasible strategy to construct AuNRs@mSiO(2)@DOTA-TATE with good photothermal conversion efficiency, targeting-SSTR2 ability, significant antitumour effects, and good biocompatibility, warranting further explorations of AuNRs@mSiO(2)@DOTA-TATE for NETs therapy applications.