BIOSCOPE Group, LAQV@REQUIMTE, Chemistry Department, NOVA School of Science and Technology, 2829-516 Caparica, Portugal.
Institut de Biotecnologia i Biomedicina, Departament de Bioquímica i de Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Int J Mol Sci. 2023 Apr 1;24(7):6612. doi: 10.3390/ijms24076612.
The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles' surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit enteric coating and studied under extreme conditions.
需要能够在保持药物效率和稳定性的同时具有针对结直肠癌（CRC）的特异性靶向性的非侵入性疗法，这使得纳米颗粒成为开发复杂和多作用抗肿瘤方法的首选载体和主要构建块。为此，我们在此报告了使用生产针对 CRC 系的新靶向方法生产组合抗肿瘤纳米疗法。为此，使用磁荧光 NANO3 纳米颗粒作为药物阿霉素（DOX）和氧氟沙星（OFLO）的组合的纳米载体。NANO3 纳米颗粒的表面用两种不同的靶向剂进行了修饰，一种是新合成的（抗 CAIX 乙酰唑胺衍生物（AZM-SH））和一种市售的（抗表皮生长因子受体（EGFR），西妥昔单抗）。细胞毒性表明，只有含 DOX 的纳米系统与游离 DOX 相比表现出显著的甚至竞争性的细胞毒性。有趣的是，用 AZM-SH 进行表面修饰促进了 HCT116 细胞系中细胞摄取的增加，甚至超过了用 Cetuximab 进行功能化的那些。结果表明，新的靶标具有作为 CRC 细胞的纳米治疗剂的高潜力，超过了商业靶标。作为概念验证，成功地将 NANO3 系统的口服形式与 Eudragit 肠溶包衣结合，并在极端条件下进行了研究。
