穿越转运机制介导的纳米颗粒主动转运到实体瘤内已被认为是增强瘤聚集和穿透的一种有前景的方法，但纳米颗粒的物理化学性质对此效应尚不清楚。在本研究中，我们采用季铵盐-芘二酰亚胺(简称PDI)-染料为内核的聚赖氨酸树状分子，通过分离式生长制备了一种单分子双成像纳米点，并且内部正交连接Gd(III)-基团的大环探针，用于依赖于表面化学特性的肿瘤入侵的荧光成像和磁共振成像(MRI)。MRI和荧光成像结果显示，醋酸酯化（G6-Ac）和寡乙二醇（G6-OEG）表面的六代纳米点具有类似的高肿瘤积累但不同的肿瘤内分布。细胞摄取和转运实验证明，G6-Ac纳米点具有较低的溶酶体困捕率（61% vs. 83%）和较高的外排比率（47% vs. 29%）与G6-OEG相比。因此，G6-Ac更有可能通过细胞转运方式进行细胞间转运，并能够到达远离血管的肿瘤区域，而G6-OEG主要通过增强渗透和滞留（EPR）效应基于被动转运进入肿瘤，而不能传递到远处的肿瘤区域。本研究表明，通过调控表面化学，可以提高纳米颗粒的肿瘤入侵能力。

The active transport of nanoparticles into solid tumors through transcytosis has been recognized as a promising way to enhance tumor accumulation and penetration, but the effect of the physicochemical properties of nanoparticles remains unclear. Herein, we develop a type of single-molecule dual imaging nanodot by divergent growth of perylenediimide (PDI)-dye-cored polylysine dendrimers and internal orthogonal conjugation of Gd(III)-based macrocyclic probes for fluorescence imaging and magnetic resonance imaging (MRI) of surface chemistry-dependent tumor entrance. The MRI and fluorescence imaging show that sixth-generation nanodots with acetylated (G6-Ac) and oligo ethylene glycol (G6-OEG) surfaces exhibit similar high tumor accumulation but different intratumor distribution. Cellular uptake and transport experiments suggest that G6-Ac nanodots have lower lysosomal entrapment (61% vs. 83%) and a higher exocytotic rate (47% vs. 29%) than G6-OEG. Therefore, G6-Ac is more likely to undergo intercellular transport through cell transcytosis, and is able to reach a tumor area distant from blood vessels, while G6-OEG mainly enters the tumor through enhanced permeability and retention (EPR) effect-based passive transport, and is not able to deliver to distant tumor areas. This study suggests that it is possible to boost the tumor entrance of nanoparticles by engineering surface chemistry for active transport.