He Yilin, Mao Zheng, Zhang Ye, Lv Haiyin, Yan Jincong, Cao Yi, Pei Renjun
CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
Nano Science and Technology Institute, University of Science and Technology of China, Suzhou 215123, China.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7752-7761. doi: 10.1021/acsabm.0c00958. Epub 2020 Oct 22.
Smart magnetic resonance imaging (MRI) contrast agents (CAs), whose MRI contrasting enhancement is variable in response to the specific stimulus from tumor tissues, possess great potential in precise tumor diagnosis. Herein, we design a type of extremely small iron oxide nanoparticle (ESIONP)-based pH-responsive system for activatable T MRI in the tumor acid microenvironment. The ESIONP system is composed of ESIONP-PEG-PGA and ESIONP-PEG-PDC, which were respectively constructed through the surface modification with poly (l-glutamic acid) (PGA) and poly(-{'-[″-(2-carbox aminoethyl)]-2-aminoethyl}glutamide) (PDC) on the surface of ESIONP. The pH-responsive system exhibits the dispersed state under the neutral condition, and when it is exposed to the weakly acid environment, ESIONP-PEG-PDC switches from the neutral to positive charge, finally leading to the aggregation by the electrostatic interaction between the positively charged ESIONP-PEG-PDC and negatively charged ESIONP-PEG-PGA. On the basis of the aggregation, the T contrasting effect of the pH-responsive system switches to a T contrasting effect, which can be employed to realize the selective enhancement of imaging contrast at the tumor location owing to the weakly acid microenvironment. Moreover, on the basis of size increase originated from the aggregation effect, the residence time of extremely small iron oxide nanoparticles (ESIONPs) in the tumor site is effectively prolonged, which is beneficial for the MRI of tumors. Therefore, the pH-responsive system based on the ESIONPs is a potential smart MRI contrast agent for accurate tumor diagnosis.
智能磁共振成像（MRI）造影剂（CAs），其MRI造影增强会根据肿瘤组织的特定刺激而变化，在精确肿瘤诊断方面具有巨大潜力。在此，我们设计了一种基于超小氧化铁纳米颗粒（ESIONP）的pH响应系统，用于在肿瘤酸性微环境中实现可激活的T MRI。ESIONP系统由ESIONP-PEG-PGA和ESIONP-PEG-PDC组成，它们分别是通过在ESIONP表面用聚（L-谷氨酸）（PGA）和聚（-{'-[″-(2-羧基氨基乙基)]-2-氨基乙基}谷氨酰胺）（PDC）进行表面修饰构建而成。该pH响应系统在中性条件下呈分散状态，当暴露于弱酸性环境时，ESIONP-PEG-PDC从电中性转变为带正电荷，最终通过带正电荷的ESIONP-PEG-PDC与带负电荷的ESIONP-PEG-PGA之间的静电相互作用导致聚集。基于这种聚集，pH响应系统的T造影效果转变为T造影效果，由于肿瘤微环境呈弱酸性，可用于实现肿瘤部位成像对比度的选择性增强。此外，基于聚集效应导致的尺寸增大，超小氧化铁纳米颗粒（ESIONPs）在肿瘤部位的停留时间得以有效延长，这有利于肿瘤的MRI检查。因此，基于ESIONPs的pH响应系统是一种用于精确肿瘤诊断的潜在智能MRI造影剂。
