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Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor

Title
Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor
Authors
Yoon, Hong YeolShin, Mm LeeShim, Man KyuLee, SangminNa, Jin HeeKoo, HeebeomLee, HyukjinKim, Jong-HoLee, Kuen YongKim, KwangmeyungKwon, Ick Chan
Ewha Authors
이혁진
SCOPUS Author ID
이혁진scopus
Issue Date
2017
Journal Title
MOLECULAR PHARMACEUTICS
ISSN
1543-8384JCR Link
Citation
vol. 14, no. 5, pp. 1558 - 1570
Keywords
metabolic glycoengineeringbioorthogonal click reactionactive tumor targetingheterogeneity
Publisher
AMER CHEMICAL SOC
Indexed
SCIE; SCOPUS WOS
Abstract
Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting-of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin alpha(v)beta(3) with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more unifornaly (similar to 92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy.
DOI
10.1021/acs.molpharmaceut.6b01083
Appears in Collections:
약학대학 > 약학과 > Journal papers
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