Tumor-targeted accumulation of ligand-installed polymeric micelles influenced by surface PEGylation crowdness
writer：Yang Xi, Chen Qixian, Yang Jinjun, Wu Sudong, Liu Jun, Li Zhen, Liu Deqiang, Chen Xiyi, Qiu Yongming
keywords：polymeric micelle, PEGylation, cyclic RGD, tumor accumulation, drug delivery
source：期刊
specific source：ACS Applied Materials & Interfaces
Issue time：2017年
With respect to the intriguing biocompatibility and the
stealthy functions of poly(ethylene glycol) (PEG), PEGylated
nanoparticulates have been intensively engineered for utilities as
drug delivery vehicles. To advocate the targeted drug transportation,
targeting ligands were strategically installed onto the surface of
PEGylated nanoparticulates. The previous in vitro investigations
revealed that the ligand-specified cell endocytosis of nanoparticulates
was pronounced for the nanoparticulates with adequately high PEG
crowdedness. The present study aims to explore insight into the
impact of PEGylation degree on in vivo tumor-targeted accumulation
activities of cRGD-installed nanoparticulates. The subsequent
investigations verified the importance of the PEGylation crowdedness
in pursuit of prolonged retention in the blood circulation post
intravenous administration. Unprecedentedly, the PEGylation crowdedness
was also identified as a crucial important parameter to pursue the tumor-targeted accumulation. A plausible reason is the
elevated PEGylation crowdedness eliciting the restricted involvement in nonspecific protein adsorption of nanoparticulates in the
biological milieu and consequently pronouncing the ligand-receptor-mediated binding for the nanoparticulates. Noteworthy was
the distinctive performance of the class of the proposed systems once utilized for transportation of the mRNA payload to the
tumors. The protein expression in the targeted tumors appeared to follow a clear PEGylation crowdedness dependence manner,
where merely 2-fold PEGylation crowdedness led to remarkably 10-fold augmentation in protein expression in tumors. Hence,
the results provided important information and implications for design of active-targeting PEGylated nanomaterials to fulfill the
targeting strategies in systemic applications.