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A Versatile Carbonic Anhydrase IX Targeting Ligand-Functionalized Porous Silicon Nanoplatform for Dual Hypoxia Cancer Therapy and Imaging

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Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, LT-10257 Vilnius, Lithuania
Division of Pharmaceutical Chemistry and Technology, Drug Research Program, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
§ Laboratory of Industrial Physics, Department of Physics, University of Turku, FI-20014 Turku, Finland
Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
Department of Pharmaceutical Science, Åbo Akademi University, FI-20520 Turku, Finland
# Department of Drug chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania
*(H.Z.) E-mail [email protected]
*(V.P.) E-mail [email protected]
*(H.A.S.) E-mail [email protected]
Cite this: ACS Appl. Mater. Interfaces 2017, 9, 16, 13976–13987
Publication Date (Web):April 6, 2017
Copyright © 2017 American Chemical Society

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    Hypoxia occurs in most solid tumors, and it has been shown to be an independent prognostic indicator of a poor clinical outcome for patients with various cancers. Therefore, constructing a nanosystem specifically targeting cancer cells under hypoxia conditions is a promising approach for cancer therapy. Herein, we develop a porous silicon (PSi)-based nanosystem for targeted cancer therapy. VD11-4-2, a novel inhibitor for carbonic anhydrase IX (CA IX), is anchored on PSi particles (VD-PSi). As CA IX is mainly expressed on the cancer cell membrane under hypoxia condition, this nanocomplex inherits a strong affinity toward hypoxic human breast adenocarcinoma (MCF-7) cells; thus, a better killing efficiency for the hypoxia-induced drug resistance cancer cell is observed. Furthermore, the release of doxorubicin (DOX) from VD-PSi showed pH dependence, which is possibly due to the hydrogen-bonding interaction between DOX and VD11-4-2. The fluorescence resonance energy transfer effect between DOX and VD11-4-2 is observed and applied for monitoring the DOX release intracellularly. Protein inhibition and binding assays showed that VD-PSi binds and inhibits CA IX. Overall, we developed a novel nanosystem inheriting several advantageous properties, which has great potential for targeted treatment of cancer cells under hypoxic conditions.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.7b04038.

    • Additional experimental details (fabrication of PSi, the selection of PEG linker, quantitative conjugating efficacy, fluorescent thermal shift assay), particles size and zeta potential changes, TEM images, VD11-4-2 and DOX fluorescence spectra; FRET spectra, protein binding and inhibition, pH changes, cell viability results (PDF)

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