Near-infrared PbS quantum dots functionalized with affibodies and ZnPP for targeted imaging and therapeutic applications
Near-infrared PbS quantum dots functionalized with affibodies and ZnPP for targeted imaging and therapeutic applications
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DOI：
10.1088/2632-959x/ac33b8
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发表时间：
2021-12-01
期刊：
影响因子：
3
通讯作者：
Turyanska, Lyudmila
中科院分区：
文献类型：
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作者：
Al-Ani, Ali W.;Zamberlan, Francesco;Turyanska, Lyudmila
我们报告了一种新的治疗诊断设备的基础上，硫化铅量子点（PbS量子点）的光发射在近红外波长范围内装饰有特异性的癌症生物标志物人表皮生长因子受体2（HER 2）和锌（II）原卟啉IX（ZnPP），联合收割机结合成像，靶向和治疗在一个纳米结构的抗体体（小6.5 kDa的蛋白质为基础的抗体替代品）。在水溶液中合成了胶体PbS量子点，其粒径约为5 nm，并在近红外波长范围内发射光致发光。通过在C末端引入两个半胱氨酸残基（Afb 2C）而突变的Z（HER 2：432）抗体用作加帽配体以形成Afb 2C-PbS QD，其对HER 2具有高结合亲和力，HER 2在包括乳腺癌在内的几种类型的癌症中过表达。Afb 2C-PbS QD通过与ZnPP缀合而进一步修饰，ZnPP充当抗癌剂。针对SKBR 3（HER 2阳性）和MDA-MB-231（HER 2正常）乳腺癌细胞测试这些QD的生物活性，结果显示ZnPP-Afb 2C官能化的PbS QD成功靶向HER 2过表达癌细胞，并由于与ZnPP缀合而诱导细胞凋亡。这些结果扩展了QD纳米平台的使用，其具有用于靶向递送的新型纳米材料的制剂以及通过直接表面-蛋白质相互作用的组合成像和治疗。
We report a new theranostic device based on lead sulfide quantum dots (PbS QDs) with optical emission in the near infrared wavelength range decorated with affibodies (small 6.5 kDa protein-based antibody replacements) specific to the cancer biomarker human epidermal growth factor receptor 2 (HER2), and zinc(II) protoporphyrin IX (ZnPP) to combine imaging, targeting and therapy within one nanostructure. Colloidal PbS QDs were synthesized in aqueous solution with a nanocrystal diameter of similar to 5 nm and photoluminescence emission in the near infrared wavelength range. The Z(HER2:432) affibody, mutated through the introduction of two cysteine residues at the C-terminus (Afb2C), was used as capping ligand to form Afb2C-PbS QDs that have a high binding affinity for HER2, which is overexpressed in several types of cancer including breast cancer. Afb2C-PbS QDs were further modified by conjugation with ZnPP, which acts as an anticancer agent. The biological activity of these QDs was tested against SKBR3 (HER2-positive) and MDA-MB-231 (HER2-normal) breast cancer cells, with results showing that ZnPP-Afb2C-functionalized PbS QDs were successfully targeted to the HER2-overexpressing cancer cells and induced cell apoptosis thanks to the conjugation with ZnPP. These results expand the use of the QD nanoplatform with the formulation of novel nanomaterials for targeted delivery and combined imaging and therapy via direct surface-protein interaction.