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

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486360.do
DOI
10.1039/c6sc05640g
Title
Toward redesigning the PEG surface of nanocarriers for tumor targeting:impact of inner functionalities on size, charge, multivalent binding,and biodistribution
Description
We are grateful to Byoungseok Min for the aid in the SAXS experimentsand Hyang Ran Yoon for the assistance with the confocal fluorescencemicroscopy and flow cytometry experiments. This work was supported bythe National Research Foundation of Korea funded by the Ministry ofScience, ICT, and Future Planning (NRF-2015M2A2A6A01044921,NRF-2012M3A9B2028334, NRF-2015-027846, and NRF-2017R1A2B2008284), theKorea Health Technology R&D Project funded by the Ministry of Health &Welfare, Republic of Korea (HI14C0311020014), and the KRIBB ResearchInitiative Program.
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 IC50 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.
provenance
Made available in Cube on 2018-09-28T16:05:31Z (GMT). No. of bitstreams: 0
language
English
author
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
accessioned
2018-09-28T16:05:31Z
available
2018-09-28T16:05:31Z
issued
2017
citation
CHEMICAL SCIENCE(8): 7
issn
2041-6520
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486360.do
Funder
보건복지부
Funding Program
질환극복기술개발
Project ID
1465020779
Jurisdiction
Rep.of Korea
Project Name
Evaluation of therapeutic efficacy of iTreg therapy on iflammatory bowel disease by mouse molecular imaging.
rights
openAccess
type
article


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