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Title 

Toward redesigning the PEG surface of nanocarriers for tumor targeting: impact of inner functionalities on size, charge, multivalent binding, and biodistribution

Authors 

Ju Young HeoS H KangY H KimSuyeon YouK S JinS W KimHye Youn JungK O JungC H LeeMi Jung KimSoo Eun SungBoram KimI S ChoiH YounJ K ChungS K KimYoonkyung Kim

Publisher 

Royal Society of Chemistry

Issue Date 

2017

Citation 

Chemical Science

Abstract 

Achieving accurate and efficacious tumor targeting with minimal off-target effects is of paramount importance in designing diagnostic and therapeutic agents for cancer. In this respect, nanocarriers have gained enormous popularity because of their attainable multifunctional features, as well as tumor-targeting potential by extravasation. However, once administered into the bloodstream, nanocarriers face various in vivo obstacles that may significantly impair their performance needed for clinical translation. Herein, we demonstrate a strategy to enhance tumor-targeting efficiency by embedding functionalities in the interior region of partially PEGylated nanocarriers (ca. 10 nm in diameter), intended for active or passive targeting. The cooperative impact of these topologically inner functional groups (IFGs) was marked: enhancements of >100-fold in IC50in vitro (e.g., a high-avidity ligand with cationic IFGs) and >2-fold in tumor accumulation at 2 h post-injection in vivo (e.g., a high-avidity ligand with anionic IFGs), both against the fully PEGylated counterpart. Analogous to allosteric modulators, properly employed IFGs may substantially improve the process of effectively directing nanocarriers to tumors, which is otherwise solely dependent on avidity or extravasation

ISSN 

2041-6520

Link 

http://dx.doi.org/10.1039/c6sc05640g

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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