Nieto Celia, Vega Milena A, Martín Del Valle Eva
Chemical Engineering Department, Faculty of Chemical Sciences, University of Salamanca, 37008 Salamanca, Spain.
Cancers (Basel). 2021 May 21;13(11):2526. doi: 10.3390/cancers13112526.
Despite the advances made in the fight against HER2-positive breast cancer, the need for less toxic therapies and strategies that avoid the apparition of resistances is indisputable. For this reason, a targeted nanovehicle for paclitaxel and trastuzumab, used in the first-line treatment of this subtype of breast cancer, had already been developed in a previous study. It yielded good results in vitro but, with the aim of further reducing paclitaxel effective dose and its side effects, a novel drug delivery system was prepared in this work. Thus, polydopamine nanoparticles, which are gaining popularity in cancer nanomedicine, were novelty loaded with paclitaxel and trastuzumab. The effectiveness and selectivity of the nanoparticles obtained were validated in vitro with different HER2-overexpressing tumor and stromal cell lines. These nanoparticles showed more remarkable antitumor activity than the nanosystem previously designed and, in addition, to affect stromal cell viability rate less than the parent drug. Moreover, loaded polydopamine nanoparticles, which notably increased the number of apoptotic HER2-positive breast cancer cells after treatment, also maintained an efficient antineoplastic effect when validated in tumor spheroids. Thereby, these bioinspired nanoparticles charged with both trastuzumab and paclitaxel may represent an excellent approach to improve current HER2-positive breast cancer therapies.
尽管在对抗HER2阳性乳腺癌方面取得了进展，但对于毒性更低且能避免产生耐药性的治疗方法和策略的需求是无可争议的。因此，在先前的一项研究中已经开发出一种用于这种亚型乳腺癌一线治疗的靶向纳米载体，用于紫杉醇和曲妥珠单抗。它在体外产生了良好的效果，但为了进一步降低紫杉醇的有效剂量及其副作用，在这项工作中制备了一种新型药物递送系统。因此，在癌症纳米医学中越来越受欢迎的聚多巴胺纳米颗粒被创新性地负载了紫杉醇和曲妥珠单抗。所获得的纳米颗粒的有效性和选择性在体外通过不同的HER2过表达肿瘤和基质细胞系进行了验证。这些纳米颗粒显示出比先前设计的纳米系统更显著的抗肿瘤活性，此外，对基质细胞活力率的影响小于母体药物。此外，负载的聚多巴胺纳米颗粒在治疗后显著增加了凋亡的HER2阳性乳腺癌细胞的数量，在肿瘤球体中验证时也保持了有效的抗肿瘤作用。因此，这些同时负载曲妥珠单抗和紫杉醇的仿生纳米颗粒可能是改善当前HER2阳性乳腺癌治疗的一种优秀方法。
