For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs.

对于聚合物纳米颗粒（NPs）向肿瘤中释放的药物比游离药物溶液要多，至关重要的是NPs与肿瘤细胞建立相互作用并避免从肿瘤中清除。由于传统的聚乙二醇（PEG）表面层会干扰肿瘤中的细胞-NP相互作用，因此我们使用了水溶性且血液相容的壳聚糖衍生物，称为两性离子壳聚糖（ZWC）作为聚乳酸-乙醇酸共聚物的替代表面涂层。酸（PLGA）NPs。ZWC涂层的PLGA NPs根据介质的pH值显示pH依赖的表面电荷分布和不同的细胞相互作用。在体内使用磁共振（MR）成像和荧光全身成像对携带LS174T异种移植物的小鼠的ZWC涂层NP的传递进行了评估，它们分别跟踪了包裹在NP中的氧化铁颗粒和吲哚菁绿（ICG）作为示踪剂。MR成像显示ZWC包被的NP在肿瘤中比PEG包被的NP更持久，这与体外结果一致。但是，荧光成像表明，由于染料的快速释放，ZWC涂层增加了NP在肿瘤中的保留率，并没有显着影响肿瘤中ICG的分布。这项研究表明，在循环过程中稳定地保留在NP中的药物是成功转化表面工程化NP潜在利益的关键先决条件。