Immunoconjugated gold nanoshell-mediated photothermal ablation of trastuzumab-resistant breast cancer cells
Immunoconjugated gold nanoshell-mediated photothermal ablation of trastuzumab-resistant breast cancer cells
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DOI：
10.1007/s10549-010-0811-5
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发表时间：
2011-01-01
影响因子：
3.8
通讯作者：
Drezek, Rebekah A.
中科院分区：
文献类型：
--
作者：
Carpin, Laura B.;Bickford, Lissett R.;Drezek, Rebekah A.
曲妥珠单抗是 FDA 批准的药物，已显示出针对 HER2+ 乳腺癌的临床疗效，通常与其他化疗药物联合使用。然而，许多患者对曲妥珠单抗具有先天耐药性，或者在治疗过程中会产生耐药性。曲妥珠单抗耐药的患者需要替代治疗。在这里，我们研究金纳米粒子介导的光热疗法作为化疗耐药癌症的潜在替代疗法。金纳米壳光热疗法利用热量破坏肿瘤细胞，这是一种物理机制，能够克服导致曲妥珠单抗耐药的细胞适应。通过在纳米壳的金表面添加抗 HER2 作为靶向方式，我们提高了纳米壳对 HER2+ 乳腺癌的特异性。将与抗 HER2 缀合的硅金纳米壳与曲妥珠单抗敏感和曲妥珠单抗耐药的乳腺癌细胞一起孵育。使用双光子激光扫描显微镜证实纳米壳结合，然后使用近红外激光消融细胞。我们展示了使用抗 HER2 偶联的二氧化硅-金纳米壳和近红外激光成功靶向和消融曲妥珠单抗耐药细胞。这项研究表明金纳米壳介导的疗法在体内治疗曲妥珠单抗耐药性乳腺癌的潜力。
Trastuzumab is a FDA-approved drug that has shown clinical efficacy against HER2+ breast cancers and is commonly used in combination with other chemotherapeutics. However, many patients are innately resistant to trastuzumab, or will develop resistance during treatment. Alternative treatments are needed for trastuzumab-resistant patients. Here, we investigate gold nanoparticle-mediated photothermal therapies as a potential alternative treatment for chemotherapy-resistant cancers. Gold nanoshell photothermal therapy destroys the tumor cells using heat, a physical mechanism, which is able to overcome the cellular adaptations that bestow trastuzumab resistance. By adding anti-HER2 to the gold surface of the nanoshells as a targeting modality, we increase the specificity of the nanoshells for HER2+ breast cancer. Silica-gold nanoshells conjugated with anti-HER2 were incubated with both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells. Nanoshell binding was confirmed using two-photon laser scanning microscopy, and the cells were then ablated using a near-infrared laser. We demonstrate the successful targeting and ablation of trastuzumab-resistant cells using anti-HER2-conjugated silica-gold nanoshells and a near-infrared laser. This study suggests potential for applying gold nanoshell-mediated therapy to trastuzumab-resistant breast cancers in vivo.