title: Microfluidic Encapsulation of Prickly Zinc-Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy.
abstract: Structural features of nanoparticles have recently been explored for different types of applications. To explore specific particles as nanomedicine and physically destroy cancer is interesting, which might avoid many obstacles in cancer treatment, for example, drug resistance. However, one key element and technical challenge of those systems is to selectively target them to cancer cells. As a proof-of-concept, Prickly zinc-doped copper oxide (Zn-CuO) nanoparticles (Prickly NPs) have been synthesized, and subsequently encapsulated in a pH-responsive polymer; and the surface has been modified with a novel synthesized ligand, 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl] benzenesulfonamide (VD1142). The Prickly NPs exhibit very effective cancer cell antiproliferative capability. Moreover, the polymer encapsulation shields the Prickly NPs from unspecific nanopiercing and, most importantly, VD1142 endows the engineered NPs to specifically target to the carbonic anhydrase IX, a transmembrane protein overexpressed in a wide variety of cancer tumors. Intracellularly, the Prickly NPs disintegrate into small pieces that upon endosomal escape cause severe damage to the endoplasmic reticulum and mitochondria of the cells. The engineered Prickly NP is promising in efficient and targeted cancer treatment and it opens new avenue in nanomedication.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.|Harvard John A. Paulson School of Applied Science and Engineering, Harvard University, Cambridge, MA, 02138, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Runrun
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, LT-10257, Vilnius, Lithuania.
authors.forename: Agne
authors.initials: A
authors.lastname: Janoniene
authors.affiliation: Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Pan
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: Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Cui
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: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, LT-10257, Vilnius, Lithuania.
authors.forename: Daumantas
authors.initials: D
authors.lastname: Matulis
authors.affiliation: Institute of Biotechnology, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, China.|Department of Chemistry, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Pan
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D000071231:Carbonic Anhydrase IX / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013096:Spermine / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D003911:Dextrans; D053769:Nanocapsules; D009363:Neoplasm Proteins; D013096:Spermine; D003300:Copper; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D015032:Zinc; C000520:cuprous oxide
keywords: Zn-doped CuO; acetalated dextran; microfluidic; mitochondria; targeted cancer therapy