Department of Health Sciences, University of Catanzaro "Magna Græcia", Campus Universitario "S. Venuta", Viale Europa, I-88100 Catanzaro, Italy; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Int J Pharm. 2021 Mar 15;597:120346. doi: 10.1016/j.ijpharm.2021.120346. Epub 2021 Feb 2.
Breast cancer, with around 2 million new cases in 2019, is the second most common cancer worldwide and the second leading cause of cancer death among females. The aim of this work is to prepare a targeting nanoparticle through the conjugation of LinTT1 peptide, a specific molecule targeting p32 protein overexpressed by breast cancer and cancer associated cells, on liposomes' surface. This approach increases the cytotoxic effects of doxorubicin (DOX) and sorafenib (SRF) co-loaded in therapeutic liposomes on both 2D and 3D breast cancer cellular models. The liposome functionalization leads to a higher interaction with 3D breast cancer spheroids than bare ones. Moreover, interaction studies between LinTT1-functionalized liposomes and M2 primary human macrophages show an internalization of 50% of the total nanovesicles that interact with these cells, while the other 50% results only associated to cell surface. This finding suggests the possibility to use the amount of associated liposomes to enrich the hypoxic tumor area, exploiting the ability of M2 macrophages to accumulate in the central core of tumor mass. These promising results highlight the potential use of DOX and SRF co-loaded LinTT1-functionalized liposomes as nanomedicines for the treatment of breast cancer, especially in triple negative cancer cells.
乳腺癌是全球第二常见的癌症，也是女性癌症死亡的第二大主要原因，其 2019 年新发病例约为 200 万例。本工作旨在通过将 LinTT1 肽（一种针对乳腺癌和癌相关细胞过度表达的 p32 蛋白的特异性分子）连接到脂质体表面，制备一种靶向纳米颗粒。这种方法增加了载有阿霉素（DOX）和索拉非尼（SRF）的治疗性脂质体在 2D 和 3D 乳腺癌细胞模型中的细胞毒性作用。脂质体的功能化导致与裸脂质体相比，与 3D 乳腺癌球体的相互作用更高。此外，LinTT1 功能化脂质体与 M2 原代人巨噬细胞之间的相互作用研究表明，与这些细胞相互作用的总纳米囊泡中有 50%被内化，而另外 50%仅与细胞表面相关。这一发现表明，有可能利用与细胞相关的脂质体的数量来富集缺氧肿瘤区域，利用 M2 巨噬细胞在肿瘤质量中心积聚的能力。这些有希望的结果突出了 DOX 和 SRF 共载 LinTT1 功能化脂质体作为治疗乳腺癌的纳米药物的潜在用途，特别是在三阴性癌细胞中。
