Toward redesigning the PEG surface of nanocarriers for tumor targeting: impact of inner functionalities on size, charge, multivalent binding, and biodistribution† †Electronic supplementary information (ESI) available: Experimental section, tables, synthetic schemes, NMR and mass spectra, SAXS profiles, cytotoxicity assay results, confocal fluorescence micrographs, and SPECT images and movies. See DOI: 10.1039/c6sc05640g Click here for additional data file. Click here for additional data file. Cl

• Published in: Chemical science (Cambridge) 2017-04, Vol.8 (7), p.5186-5195
• Main Authors: Heo, Ju Young, Kang, Se Hun, Kim, Young-Hwa, You, Suyeon, Jin, Kyeong Sik, Kim, Seung Won, Jung, Hye-youn, Jung, Kyung Oh, Lee, Chul-Hee, Kim, Mi Jung, Sung, Soo-Eun, Kim, Boram, Choi, Insung S., Youn, Hyewon, Chung, June-Key, Kim, Seok-ki, Kim, Yoonkyung
• Format: Article
• Language: English
• Subjects: Chemistry
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c6sc05640g

A simple strategy to enhance the tumor-targeting efficiency of PEGylated nanocarriers is demonstrated. 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 IC 50 in 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.