光声/光热增强的黑TiO2@金星光响应纳米探针及三阴乳腺癌靶向可视化诊疗研究

Photoacoustic (PA) imaging and photothermal therapy (PTT) based on near infrared (NIR) light-responsive nanoprobes have important application in visualizing theranostics of cancers. However, the disadvantages of low photo conversion efficiency of nanomaterials and non-specific heating damage induced by high-flux light irradiation restrict their application of NIR-responsive nanoprobes in biomedicine. In this project, using the excellent PA imaging and PTT of black TiO2 and Au nanostars, PA/photothermal improved NIR-responsive nanoprobes of black TiO2@Au nanostars with core@shell structure are constructed for targeted PA imaging/PTT of triple-negative breast cancer under the irradiation of low-flux NIR light. This project will mainly focus on three aspects: (1) Investigating the effect of interfacial interaction between black TiO2 and Au nanostars on the synergistic enhancement of PA/photothermal performance. (2) Exploring the mechanism of decreasing the non-specific uptake of normal cells and increasing the specific uptake of triple-negative breast cancer cells by conjugating RE-1/CK3 double peptides. (3) Illuminating the relationship between nanoprobe dose, light flux and PA imaging/PTT performance. The as-constructed NIR-responsive nanoprobes based on black TiO2@Au nanostars with high photo conversion efficiency will be important for the safe, high-efficient, and targeted PA imaging/PTT of triple-negative breast tumor under the irradiation of low-flux NIR light.

基于近红外光响应纳米探针的光声(PA)成像和光热治疗(PTT)在肿瘤可视化诊疗中具有重要的应用前景。然而，纳米材料的“低光转换效率”以及高通量光辐照引起的组织“非特异性热损伤”缺陷对光响应纳米探针的应用带来严峻挑战。本项目拟利用黑二氧化钛(TiO2)和金纳米星优异的PA成像/PTT性能，构建PA/光热性能增强的黑TiO2@金星核壳结构光响应纳米探针，实现在低通量近红外光辐照下对三阴乳腺癌的靶向PA成像/PTT。重点研究黑TiO2与金星之间的界面相互作用对PA/光热协同增强的影响；揭示RE-1/CK3双肽偶联对降低正常细胞非特异性摄取、提高三阴乳腺癌细胞靶向摄取的作用机制；阐明纳米探针注射剂量、光辐照通量与PA成像/PTT性能之间的关系。本项目构建的具有高光转换效率的黑TiO2@金星复合光响应纳米探针，对实现在低通量近红外光辐照下三阴乳腺癌的安全、高效靶向PA成像/PTT具有重要的意义。

基于近红外光响应纳米探针的光声（PA）成像和光热治疗（PTT）在肿瘤可视化诊疗中具有重要的应用前景。然而，纳米材料的“低光转换效率”以及高通量光辐照引起的组织“非特异性热损伤”缺陷对光响应纳米探针的应用带来严峻挑战。本项目利用黑色二氧化钛（TiO2）和金纳米星（AuNSs）优异的光声成像/PTT性能，不仅构建了光声/光热性能增强的光响应纳米探针，而且实现了在低通量808 nm近红外光辐照下对三阴乳腺癌的特异性靶向P成像/PTT。取得的主要创新性研究结果如下：（1）构建了基于黑色TiO2的纳米探针2种，实现了在低通量808 nm近红外光辐照下对乳腺癌的磁共振（MR）成像、光动力治疗（PDT）和PTT。（2）构建了基于AuNSs（金纳米双锥（AuNBPs））的PA/光热增强的纳米探针2种，实现了对乳腺癌增强的PA成像/PTT以及协同PDT和化疗。（3）构建了ZD2短肽偶联的、基于金纳米星的纳米探针，实现了对三阴乳腺癌的特异性靶向MR成像和PTT。（4）构建了介孔硅封装金簇并包裹二氧化锰的纳米探针，实现了对乳腺癌H2O2响应的“关-开”MR成像和增强的PDT。依托本项目，以第一/（共同）通讯作者身份在国际SCI期刊发表论文11篇，在国内期刊发表论文2篇；发表英文专著章节1篇；申请中国发明专利2项；培养（已毕业）硕士研究生5名。本项目构建的PA/光热增强的纳米探针对于提高乳腺癌的可视化诊疗性能具有重要的意义。