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Sequential activation of anticancer therapy triggered by tumor microenvironment-selective imaging

Authors
Shim, GayongQuoc-Viet LeSuh, JuhanChoi, SunheeKim, GunwooChoi, Han-GonKim, Young BongMacgregor, Robert B., Jr.Oh, Yu-Kyoung
Issue Date
Mar-2019
Publisher
ELSEVIER SCIENCE BV
Keywords
Selective imaging; Sequential activation; Anticancer therapy; Nanosheets; Tumor microenvironment
Citation
JOURNAL OF CONTROLLED RELEASE, v.298, pp.110 - 119
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF CONTROLLED RELEASE
Volume
298
Start Page
110
End Page
119
URI
https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/3404
DOI
10.1016/j.jconrel.2019.02.012
ISSN
0168-3659
Abstract
The combination of imaging and anticancer therapy has recently emerged as a promising strategy. However, nonspecific imaging signals and distribution of anticancer drugs at normal tissues limit the specificity of the combination therapy. To overcome the challenges, we designed a system which can selectively visualize cancer tissues and initiate the subsequent action of therapeutic molecules in tumor microenvironment. Exploiting the overexpression of matrix metalloproteinase (MMP) in the tumor microenvironment, we designed a graphene oxide (GO)-based nanosheet system loaded with a pegylated MMP-cleavable imaging probe and an anticancer peptide shielded under the imaging probe. GO loaded with pegylated imaging probe derivative and anticancer buforin IIb peptide (IPGO/BF) was not fluorescent and BF hidden within pegylated surfaces did not exert anticancer activity. However, in tumor microenvironment, IPGO/BF selectively provided imaging by liberating pegylated fluorescent moiety. The cleavage of MMP-sensitive peptide triggered imaging signal and subsequent exposure of shielded BF on GO and enhanced its therapeutic function. SCC7 tumor-bearing mice treated with IPGO/BF exhibited selective fluorescence in tumor tissues, and greater imaging signal-dependent antitumor effects compared with other groups. The selective imaging-dependent sequential activation of anticancer therapy in tumor microenvironment would be a feasible strategy to reduce the nonspecific false-positive signals of tumor imaging and undesirable side effects of anticancer drugs at normal tissues.
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