title: A Versatile Carbonic Anhydrase IX Targeting Ligand-Functionalized Porous Silicon Nanoplatform for Dual Hypoxia Cancer Therapy and Imaging.
abstract: 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.
authors.affiliation: 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.
authors.forename: Agne
authors.initials: A
authors.lastname: Janoniene
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Drug Research Program, Faculty of Pharmacy, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University , LT-10257 Vilnius, Lithuania.
authors.forename: Lina
authors.initials: L
authors.lastname: Baranauskiene
authors.affiliation: Laboratory of Industrial Physics, Department of Physics, University of Turku , FI-20014 Turku, Finland.
authors.forename: Ermei
authors.identifier: http://orcid.org/0000-0002-8300-6533
authors.initials: E
authors.lastname: Mäkilä
authors.affiliation: Shanghai Institute of Ceramics, Chinese Academy of Sciences , Shanghai 200050, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: Laboratory of Industrial Physics, Department of Physics, University of Turku , FI-20014 Turku, Finland.
authors.forename: Jarno
authors.identifier: http://orcid.org/0000-0002-5245-742X
authors.initials: J
authors.lastname: Salonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Drug Research Program, Faculty of Pharmacy, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Drug Research Program, Faculty of Pharmacy, University of Helsinki , FI-00014 Helsinki, Finland.|Department of Pharmaceutical Science, Åbo Akademi University , FI-20520 Turku, Finland.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University , LT-10257 Vilnius, Lithuania.|Department of Drug chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences , LT-44307 Kaunas, Lithuania.
authors.forename: Vilma
authors.initials: V
authors.lastname: Petrikaite
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Drug Research Program, Faculty of Pharmacy, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Hélder A
authors.identifier: http://orcid.org/0000-0001-7850-6309
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000951:Antigens, Neoplasm; D000071231:Carbonic Anhydrase IX / Q000737:chemistry*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004317:Doxorubicin; D006801:Humans; D012825:Silicon
chemical_list: D000951:Antigens, Neoplasm; D004317:Doxorubicin; D000071231:Carbonic Anhydrase IX; D012825:Silicon
keywords: FRET; carbonic anhydrase IX; drug resistance; hypoxia targeting; porous silicon particles