Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, 20126 Milano, Italy.
Pharmacol Res. 2010 Aug;62(2):150-65. doi: 10.1016/j.phrs.2010.01.013. Epub 2010 Feb 1.
At present, mammary carcinoma is the second most common type of malignant tumor in adult women after lung cancer, as more than one million women are diagnosed with breast cancer every year. Despite advances in diagnosis and treatment, which have resulted in a decrease in mortality in recent decades, breast cancer remains a major public health problem. One of the most significant unresolved clinical and scientific problems is the occurrence of resistance to clinical treatments and their toxicity (and how to predict, prevent and overcome them). However, the heterogeneity of human breast cancer in terms of genetic features, molecular profiles and clinical behavior represents a constraint obstructing the discovery of a solution to the disease. It is currently considered that the chances of success of therapy may increase if the tumor cells are selectively removed before they can evolve to their mature stages up to metastases production. Therefore, novel and more sensitive diagnostic tools are being developed, with the aim of improving the early and noninvasive detection of rising malignancies and the accuracy of tumor tissue localization. Meanwhile, there is an emerging use of targeted therapies in oncology, depending on the expression of specific proteins or genes present in tumor cells. Among the molecular targets considered for the treatment of breast cancer cells so far, we chose to focus on examples involving overexpression and/or gene amplification of "Human Epidermal growth factor Receptor 2" (HER2) protein. In current studies, various types of nanoparticles conjugated with the anti-HER2 monoclonal antibody, the so-called "trastuzumab", are investigated extensively due to promising results in biological and preclinical applications aimed at improving the treatment of breast cancer. In this paper, we present a critical review of the preparation and use of different kinds of trastuzumab-functionalized nanoparticles, with an emphasis on the therapeutic and diagnostic (theranostic) potential of this generation of hybrid nanoparticles, exploiting the multifaceted mechanisms of action of trastuzumab against malignant cells.
目前，乳腺癌是成年女性继肺癌之后第二大常见的恶性肿瘤类型，每年有超过 100 万女性被诊断患有乳腺癌。尽管在诊断和治疗方面取得了进展，导致近几十年来死亡率有所下降，但乳腺癌仍然是一个主要的公共卫生问题。其中一个最重大的未解决的临床和科学问题是对临床治疗的耐药性及其毒性（以及如何预测、预防和克服它们）的发生。然而，人类乳腺癌在遗传特征、分子谱和临床行为方面的异质性是阻碍发现该疾病解决方案的一个限制因素。目前认为，如果肿瘤细胞在进化到产生转移之前被选择性地去除，那么治疗的成功率可能会增加。因此，正在开发新的、更敏感的诊断工具，目的是提高对不断发展的恶性肿瘤的早期和非侵入性检测以及肿瘤组织定位的准确性。与此同时，在肿瘤学中，基于存在于肿瘤细胞中的特定蛋白质或基因的表达，出现了靶向治疗的应用。在迄今为止考虑用于治疗乳腺癌细胞的分子靶标中，我们选择集中研究涉及“人表皮生长因子受体 2”（HER2）蛋白过度表达和/或基因扩增的例子。在当前的研究中，由于针对改善乳腺癌治疗的生物和临床前应用的有前途的结果，各种与抗 HER2 单克隆抗体（即曲妥珠单抗）缀合的纳米粒子受到了广泛的研究。在本文中，我们对不同类型的曲妥珠单抗功能化纳米粒子的制备和使用进行了批判性回顾，重点介绍了这一代杂交纳米粒子的治疗和诊断（治疗诊断）潜力，利用了曲妥珠单抗针对恶性细胞的多方面作用机制。
