IONs can accumulate in tumor sites

离子可以通过被动或主动靶向在肿瘤部位积累。当纳米颗粒可以从血流中渗出并通过增强的渗透性和保留 (EPR) 效应进入肿瘤细胞时，就会发生被动靶向 [134,135]。另一方面，外加磁场的主动靶向利用磁性纳米粒子对磁场的响应性 [136,137]。离子还可以用合成和天然聚合物 [130,138,139]、表面活性剂和脂肪酸 [31,140] 包被，并用靶向配体进行功能化 [130,141]，这允许将这些纳米颗粒用作具有改进选择性和药代动力学的药物递送系统 [142,143]。<br><br>超顺磁特性要求纳米颗粒具有小尺寸，最好低于~20 nm [4]。然而，在这个尺寸下，纳米颗粒的磁矩很小，因此磁响应可能会受到影响。将单个纳米粒子自组装成纳米团簇是克服这个问题的一种可能策略。克拉利等人。[144] 从磁赤铁矿 (γ-Fe2O3) 的纳米团簇中开发出纳米链和纳米束，具有保留的超顺磁性、零矫顽力和良好的胶体稳定性。其他细长结构，如纳米管或纳米棒，也正在研究用于药物递送。氧化铁纳米棒由于其超顺磁性行为 [145] 和具有控释特性和生物相容性的细胞内递送能力而受到关注 [146]。

IONs can accumulate in tumor sites by passive or active targeting. Passive targeting occurs when nanoparticles can extravasate from the bloodstream and enter in tumor cells through the enhanced permeability and retention (EPR) effect [134,135]. On the other hand, active targeting with an applied magnetic field takes advantage on the responsiveness of magnetic nanoparticles towards a magnetic field [136,137]. IONs can also be coated with synthetic and natural polymers [130,138,139], surfactants and fatty acids [31,140] and functionalized with targeting ligands [130,141], which allows the use of these nanoparticles as drug delivery systems with improved selectivity and pharmacokinetics [142,143].The superparamagnetic properties demand that nanoparticles have small sizes, preferably below ~20 nm [4]. However, at this size, magnetic moments of nanoparticles are small, so magnetic response can be compromised. Self-assembly of individual nanoparticles into nanoclusters is one possible strategy to overcome this problem. Kralj et al. [144] developed nanochains and nanobundles from nanoclusters of maghemite (γ-Fe2O3) with preserved superparamagnetism, zero coercivity and good colloidal stability. Other elongated structures, like nanotubes or nanorods, are also being investigated for drug delivery. Iron oxide nanorods have attracted attention due to their superparamagnetic behavior [145] and capacity of intracellular delivery with controlled-release profile and biocompatibility [146]. Nanotubes have the advantage of enabling the loading of large amounts of bioactive compounds in their inner voids, while the outer surface can be coated or functionalized with targeting ligands (Figure 6A,B) [147].<br>

离子可以通过被动或主动靶向在肿瘤部位积累。当纳米粒子可以从血流中溢出并通过增强的渗透性和保留(EPR)效应进入肿瘤细胞时，就会发生被动靶向[134，135]。另一方面，施加磁场的主动靶向利用磁性纳米粒子对磁场的响应性[136，137]。离子也可以用合成和天然聚合物[130，138，139]、表面活性剂和脂肪酸[31，140]进行包覆，并用靶向配体[130，141]进行功能化，这使得这些纳米粒子可以用作具有改善的选择性和药代动力学的药物递送系统[142，143]。超顺磁性要求纳米粒子具有小尺寸，优选小于20纳米[4]。然而，在这个尺寸下，纳米粒子的磁矩很小，因此磁响应可能会受到影响。单个纳米粒子自组装成纳米团簇是克服这个问题的一种可能策略。Kralj等人[144]从磁赤铁矿(γ-Fe2O3)的纳米团簇中开发了纳米链和纳米束，具有保持的超顺磁性、零矫顽力和良好的胶体稳定性。其他细长结构，如纳米管或纳米棒，也正在研究用于药物输送。氧化铁纳米棒由于其超顺磁性[145]和具有控制释放特性和生物相容性的细胞内递送能力[146]而引起了人们的关注。纳米管的优点是能够在其内部空隙中装载大量生物活性化合物，而外表面可以用靶向配体涂覆或功能化(图6A，B) [147]。