Doxorubicin-Conjugated lmmuno-Nanoparticles for Intracellular Anticancer Drug Delivery
Doxorubicin-Conjugated lmmuno-Nanoparticles for Intracellular Anticancer Drug Delivery
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DOI：
10.1002/adfm.200801271
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发表时间：
2009-06-09
影响因子：
19
通讯作者：
Shoichet, Molly S.
中科院分区：
文献类型：
--
作者：
Shi, Meng;Ho, Karyn;Shoichet, Molly S.
包含表面呋喃基团的聚合物纳米颗粒用于通过Diels-Alder（DA）偶联化学结合靶向抗人表皮生长因子受体2（抗HER 2）抗体和化疗多柔比星（DOX）两者，用于DOX的靶向细胞内递送。在这种新的递送方法中，其中化疗剂和靶向配体首次附着于递送载体的表面，证明了DOX在HER 2过表达乳腺癌SKBR-3细胞中的核定位，如通过共聚焦激光扫描显微镜所确定的。流式细胞术分析显示，缀合的DOX保持其生物学功能，并在SKBR-3细胞中诱导与游离DOX相似的凋亡进展。与不同纳米颗粒制剂孵育后SKBR-3癌细胞的活细胞计数表明，组合的DOX和抗HER 2纳米颗粒比单独具有DOX或抗HER 2的纳米颗粒制剂更有效。虽然游离DOX对癌性SKBR-3细胞和健康HMEC-1细胞显示出相似的细胞毒性，但组合的DOX-抗HER 2纳米颗粒对SKBR-3细胞的细胞毒性显著高于HMEC-1细胞，表明纳米颗粒缀合的DOX对于细胞类型特异性靶向的益处。DOX缀合的免疫纳米颗粒代表了用于化疗剂和抗体的局部共递送的全新方法。
A polymeric nanoparticle comprised of surface furan groups is used to bind, by Diels-Alder (DA) coupling chemistry both targeting anti-human epidermal growth factor receptor 2 (anti HER2) antibodies and chemotherapeutic doxorubicin (DOX) for targeted, intracellular delivery of DOX. In this new approach for delivery, where both chemotherapeutic and targeting ligand are attached, for the first time, to the surface of the delivery vehicle, the nuclear localization of DOX in HER2-overexpressing breast cancer SKBR-3 cells is demonstrated, as determined by confocal laser scanning microscopy. Flow cytometric analysis shows that the conjugated DOX maintains its biological function and induces similar apoptotic progression in SKBR-3 cells as free DOX. The viable cell counts of SKBR-3 cnacer cells following incubation with different nanoparticle formulations demonstrates that the combined DOX and anti-HER2 nanoparticle is more efficacious than the nanoparticle formulation with either DOX or anti-HER2 alone. While free DOX shows similar cytotoxicity against both cancerous SKBR-3 cells and healthy HMEC-1 cells, the combined DOX-anti-HER2 nanoparticle is significantly more cytotoxic against SKBR-3 cells than HMEC-1 cells, suggesting the benefit of nanoparticle-conjugated DOX for cell type-specific targeting. The DOX-conjugated immuno-nanoparticle represents an entirely new method for localized co-delivery of chemotherapeutics and antibodies.