Establishment of a hTfR mAb-functionalized HPPS theranostic nanoplatform
Establishment of a hTfR mAb-functionalized HPPS theranostic nanoplatform
复制标题
hTfR mAb 功能化 HPPS 治疗诊断纳米平台的建立。
DOI：
10.7150/ntno.41741
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发表时间：
2020-01-01
期刊：
影响因子：
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通讯作者：
Lei, Ping
中科院分区：
文献类型：
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作者：
He, Qi;Guo, Zilong;Lei, Ping
原理：在癌症治疗中，人们已经做出了许多努力来开发配体导向的纳米诊疗试剂，它能够提供治疗和诊断功能以及针对肿瘤的靶向性。靶向转铁蛋白受体（TfR）的诊疗纳米平台是一种有效的系统，可将诊断和治疗药物良好地递送至恶性肿瘤部位。
方法：为了使治疗和诊断能够结合应用于许多TfR⁺肿瘤，制备了人转铁蛋白受体（hTfR）单克隆抗体（mAb）功能化的HPP纳米颗粒（HPPS - mAb），其外壳连接hTfR mAb，核心包含荧光团DiR - BOA。通过免疫染色在体外研究其靶向特异性，并使用双肿瘤移植小鼠模型在体内进行研究。通过逆转录聚合酶链反应（RT - PCR）和蛋白质印迹法测定HPPS - mAb/siRNA对HepG2细胞的影响。
结果：HPPS - mAb能够通过TfR特异性靶向癌细胞，并在早期有价值的时间节点实现肿瘤聚集，从而有效地将治疗性survivin siRNA递送至TfR⁺ HepG2细胞并介导细胞凋亡。DiR - BOA可作为一种成像工具用于癌症诊断。
结论：我们的研究为肿瘤分子成像和TfR靶向肿瘤治疗提供了一种有前景的TfR mAb导向的诊疗纳米平台候选物。
Rational: Many efforts have been made to develop ligand-directed nanotheranostics in cancer management which could afford both therapeutic and diagnostic functions as well as tumor-tailored targeting. Theranostic nanoplatform targeting transferrin receptor (TfR) is an effective system for favorable delivery of diagnostic and therapeutic agents to malignancy site.Methods: To enable amalgamation of therapy and diagnosis to many TfR+ tumor, hTfR (human TfR) monoclonal antibody (mAb)-functionalized HPPS nanoparticle (HPPS-mAb) was prepared with hTfR mAb on the shell and with fluorophore DiR-BOA in the core. The targeting specificity was investigated in vitro by immunostaining and in vivo using a double-tumor-engrafted mouse model. HPPS-mAb/siRNA effect on HepG2 cells was determined by RT-PCR and western blot.Results: HPPS-mAb could specifically target cancer cells through TfR and achieve tumor accumulation at an early valuable time node, thus efficiently delivering therapeutic survivin siRNA into TfR+ HepG2 cells and mediating cell apoptosis. DiR-BOA can act as an imaging tool to diagnose cancer.Conclusions: Our studies provide a promising TfR mAb-directed theranostic nanoplatform candidate in tumor molecular imaging and in TfR targeted tumor therapy.