Sequential activation of anticancer therapy triggered by tumor microenvironment-selective imaging
| Autor: | Gunwoo Kim, Quoc-Viet Le, Sunhee Choi, Yu-Kyoung Oh, Robert B. Macgregor, Han-Gon Choi, Juhan Suh, Young Bong Kim, Gayong Shim |
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| Rok vydání: | 2019 |
| Předmět: |
Combination therapy
Pharmaceutical Science Antineoplastic Agents Peptide 02 engineering and technology Matrix metalloproteinase Fluorescence Mice 03 medical and health sciences Cell Line Tumor Tumor Microenvironment medicine Animals Distribution (pharmacology) 030304 developmental biology chemistry.chemical_classification Mice Inbred C3H 0303 health sciences Tumor microenvironment Chemistry Proteins Cancer 021001 nanoscience & nanotechnology medicine.disease Matrix Metalloproteinases Nanostructures Head and Neck Neoplasms Cancer research Female Graphite Imaging Signal 0210 nano-technology |
| Zdroj: | Journal of Controlled Release. 298:110-119 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2019.02.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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