Here, temperature-sensitive hybrid poly(N-isopropylacrylamide) (pNIPAM) nanosystems with magnetic response are synthesised and investigated for controlled release of 5-fluorouracil (5FU) and oxaliplatin (OXA). Initially, magnetic nanoparticles (@Fe3O4) are synthesised by co-precipitation approach and functionalised with acrylic acid (AA), 3-butenoic acid (3BA) or allylamine (AL) as comonomers. The thermo-responsive polymer is grown by free radical polymerisation using N-isopropylacrylamide (NIPAM) as monomer, N,N'-methylenbisacrylamide (BIS) as cross-linker, and 2,2'-azobis(2-methylpropionamidene) (V50) as initiator. We evaluate particle morphology by transmission electron microscopy (TEM) and particle size and surface charge by dynamic light scattering (DLS) and Z-potential (ZP) measurements. These magnetically active pNIPAM@ nanoformulations are loaded with 5-fluorouracil (5FU) and oxaliplatin (OXA) to determine loading efficiency, drug content and release as well as the cytotoxicity against T-84 colon cancer cells. Our results show high biocompatibility of pNIPAM nanoformulations using human blood cells and cultured cells. Interestingly, the pNIPAM@Fe3O4-3BA + 5FU nanoformulation significantly reduces the growth of T-84 cells (57% relative inhibition of proliferation). Indeed, pNIPAM-co-AL@Fe3O4-AA nanosystems produce a slight migration of HCT15 cells in suspension in the presence of an external magnetic field. Therefore, the obtained hybrid nanoparticles can be applied as a promising biocompatible nanoplatform for the delivery of 5FU and OXA in the improvement of colon cancer treatments.

中文翻译：

---

磁性活性pNIPAM纳米系统是对温度敏感的生物相容性结构，用于控制药物的输送。

在这里，合成了具有磁响应的温度敏感性杂化聚（N-异丙基丙烯酰胺）（pNIPAM）纳米系统，并研究了其对5-氟尿嘧啶（5FU）和奥沙利铂（OXA）的控制释放。最初，磁性纳米粒子（Fe3O4）是通过共沉淀法合成的，并以丙烯酸（AA），3-丁烯酸（3BA）或烯丙胺（AL）作为共聚单体进行官能化。通过使用N-异丙基丙烯酰胺（NIPAM）作为单体，N，N'-亚甲基双丙烯酰胺（BIS）作为交联剂和2,2'-偶氮双（2-甲基丙酰胺）（V50）进行自由基聚合来生长热敏性聚合物作为发起者。我们通过透射电子显微镜（TEM）评估颗粒形态，并通过动态光散射（DLS）和Z电位（ZP）测量来评估颗粒大小和表面电荷。这些具有磁性的pNIPAM @纳米制剂装有5-氟尿嘧啶（5FU）和奥沙利铂（OXA），以确定装载效率，药物含量和释放以及对T-84结肠癌细胞的细胞毒性。我们的结果表明，使用人血细胞和培养细胞的pNIPAM纳米制剂具有高度的生物相容性。有趣的是，pNIPAM @ Fe3O4-3BA + 5FU纳米制剂显着降低了T-84细胞的生长（相对增殖抑制率为57％）。实际上，在存在外部磁场的情况下，pNIPAM-co-AL @ Fe3O4-AA纳米系统会在悬浮状态下产生少量HCT15细胞迁移。因此，所获得的杂化纳米颗粒可以用作有希望的生物相容性纳米平台，用于在改善结肠癌治疗中递送5FU和OXA。