文献：A Novel TMTP1-modifi ed Theranostic Nanoplatform for Targeted in Vivo NIR-II Fluorescence Imagingguided Chemotherapy of Cervical Cancer

文献链接：https://pubmed.ncbi.nlm.nih.gov/34988561/

作者：Alifu Nuernisha,Rong Ma,Lijun Zhu ,Zhong Du ,Shuang Chen ,Ting Yan ,Gulinigaer Alimu ,Linxue Zhang ,Cailing Ma ,Xueliang Zhang

相关产品：

HSPC、DOX、TMTP1

原文摘要：Background：Near-infrared ll (NlR-l, 900-1700 nm) fluorescence bioimaging with advantages of good biosafety.excellent spatial resolution, high sensitivity and contrast, has attracted great attentions in biomedicalresearch fields. However, most nanoprobes used for NlR-ll fluorescence imaging have poor tumortargeting ability and therapeutic efficiency. To overcome these limitations, a novel NlR-llemissivetheranostic nanoplatform for imaging and treatment of cervical cancer was designed and prepared. TheNlR-ll-emissive dye lR-783 and chemotherapy drug doxorubicin (D0X) were encapsulated into liposomesand the tumor-targeting peptide TMTP1 was conjugated to the surface of the liposomes to fomm IR-783-DOX-TMTP1 nanoparticles (NPs) via self-assembly methods.Results：The IR-783-D0X-TMTP1 NPs showed strong NlR-l emission, excellent biocompatibility, a long lifetime,and low toxicity. Further, high-definition NlR-ll fluorescence microscopy images of ear blood vessels andintratumor blood vessels were obtained from |R-783-D0X-TMTP1 NPs-stained mice with high spatialresolution under 808 nm laser excitation. Moreover, IR-783-DOX-TMTP1 NPs showed strong tumortargeting ability and high efficiently chemotherapeutic character towards cervical tumors.Conclusions：The novel targeting and NlR-+emissive lR-783-D0X-TMTP1 NPs have potential in diagnosis and

therapyfor cervical cancer.

近红外II（NIR-II，900-1700 nm）荧光生物成像具有良好的生物安全性、空间分辨率好、灵敏度和对比度高等优点，但大多数用于NIR-II荧光荧光成像的纳米探针的tumor靶向能力和Treatment 效率较差。为了克服这些限制，设计并制备了一种用于成像和NIR-ii发射纳米平台。将NIR-ii发射染料IR-783和阿霉素（DOX）封装到脂质体中，将tumor靶向肽TMTP1偶联到脂质体表面，形成IR-783- DOX-TMTP1纳米颗粒（NPs）。

改性IR-783纳米粒子的制备

制备783-DOX NPs： HSPC/DSPE-PEG（2K）和IR-783以一定比例氯仿混合溶解，然后将混合物转移到溶液中，搅拌蒸发，在溶液底部形成膜，制备脂质体。然后加入(NH4)2SO4 s溶液进行水化。将去离子水进一步放入混合物中。之后，溶液被超声并通过薄膜。然后将脂质体放入透析装置透析过夜。然后，取出脂质体，放入溶液中，加入DOX溶液，油浴中孵育加入Triton X-100破膜，分别用IR-783和DOX制备标准曲线，测定脂质体中IR-783和DOX的含量。

IR-783-TMTP1 NPs的制备：脂质体合成过程后，进一步预制备DSPE-PEG-TMTP1，适量的TMTP1多肽与DSPE-PEG-MAL混合，透析后将脂质体放入透析装置中去除未包覆的IR-783。最后，补充去离子水，取脂质体溶液，加入Triton X-100破膜，用IR-783制备标准曲线，测定脂质体中IR-783的含量。

IR-783-TMTP1-DOX NPs的制备：将TMTP1肽与DSPE-PEG-MAL在去离子水中反应；然后透析混合物得到DSPE-PEG-TMTP1。然后将磷脂、胆固醇和IR-783溶解在氯仿中，并通过蒸发旋转形成薄膜。将DSPE-PEG-TMTP1和硫酸铵进入膜中，得到脂质体。脂质体在PBS中透析2。将DOX加入到水溶液中孵育，获得了IR-783-DOX-TMTP1 NPs。

图：IR-783-DOX-TMTP1 NPs在水相分散体中的DLS研究

结论：IR-783-DOX-TMTP1 NPs具有较强的NIR-II发射能力、良好的生物相容性、寿命长。此外，在808 nm激光激发下，从IR-783-DOX-TMTP1NPs染色的小鼠中获得了高空间分辨率的高识别NIR-II型荧光显微镜图像。此外，IR-783-DOX-TMTP1 NPs对宫颈tumor具有较强的tumor靶向能力和较强的高效Chemotherapy 特性。