需要新的策略来构建多功能纳米载体，以克服靶向输送的多重挑战，用于癌症治疗。本研究探讨了带有主链季铵盐基团（离子烷）的聚氨酯作为靶向药物输送的新载体的优点。我们开发了一种新型阳离子大豆油基聚氨酯离子烷纳米载体（CPUI），可作为有效的抗癌剂，并有效地传递抗癌药物5-氟尿嘧啶（5FU）。我们还报道了一种针对叶酸受体的潜在抗癌药物输送系统。在4T1（小鼠乳腺癌细胞系）和NIH-3T3（小鼠成纤维细胞系）的无细胞药复合物的体外实验中，癌细胞的细胞毒性高，但正常成纤维细胞的细胞毒性很低。CPUI纳米颗粒很容易在水中通过离子烷的阳离子季铵基团和阴离子5FU之间的静电相互作用被装载5FU（5FU-CPUI）。对于有肿瘤的老鼠的体内研究表明，空白的CPUI载体明显抑制了肿瘤的生长，甚至比自由药物（5FU）更有效。当载体装载5FU时，对肿瘤生长的抑制作用略微增强。通过与离子烷的季铵盐基团的溴盐离子离子交换，将叶酸（FA）添加为靶向基团，进一步增强了抑制效果。结果表明，FA-CPUI-5FU纳米颗粒作为药物输送载体，可以通过叶酸受体介导的内吞作用增强在4T1细胞中的有效靶向输送，这些新型纳米载体可提供一种潜在的平台，用于有效的靶向药物输送到肿瘤组织和乳腺癌治疗的临床应用。 版权所有©2023作者。由Elsevier B.V.出版。保留所有权利。

New strategies for constructing versatile nanocarriers are needed for cancer therapy to overcome the multiple challenges of targeted delivery. This work explores the advantages of polyurethane with main-chain quaternary ammonium salt moieties (ionene) as a novel carrier for targeted drug delivery. We have developed a novel cationic soybean oil-based polyurethane ionene nanocarrier (CPUI) that can act as an effective anticancer agent and efficiently deliver the anticancer drug 5-fluorouracil (5FU). We also report a potential anticancer drug delivery system targeting the folate receptor. In vitro experiments with blank CPUI carriers on the 4T1 (mouse breast cancer cell line) and the NIH-3T3 (mouse fibroblast cell line) revealed high cytotoxicity for the cancer cells but only low cytotoxicity for the normal fibroblast cells. The CPUI nanoparticles were readily loaded with 5FU (5FU-CPUI) in water using electrostatic interactions between the cationic quaternary ammonium groups of ionene and the anionic 5FU. The in vivo study in mice with tumors showed that the blank CPUI carriers significantly inhibited tumor growth, even more than the free drug (5FU). The inhibitory effect on tumor growth was slightly enhanced when the carriers were loaded with 5FU. The prepared nanoparticles had a high loading capacity of 41.8 %. Further enhancement of the inhibitory effect was observed when folic acid (FA) was added as a targeting moiety to the system via ion exchange with the bromine counterion of the quaternary ammonium moieties. The results suggest that the efficacy of FA-CPUI-5FU nanoparticles as vehicles for drug delivery can be enhanced via folate receptor (FR) mediated endocytosis in 4T1 cells and these novel nanocarriers may provide a potential platform for effective targeted drug delivery to tumor tissue and breast cancer therapy in the clinic.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.