title: Quercetin-Based Modified Porous Silicon Nanoparticles for Enhanced Inhibition of Doxorubicin-Resistant Cancer Cells.
abstract: One of the most challenging obstacles in nanoparticle's surface modification is to achieve the concept that one ligand can accomplish multiple purposes. Upon such consideration, 3-aminopropoxy-linked quercetin (AmQu), a derivative of a natural flavonoid inspired by the structure of dopamine, is designed and subsequently used to modify the surface of thermally hydrocarbonized porous silicon (PSi) nanoparticles. This nanosystem inherits several advanced properties in a single carrier, including promoted anticancer efficiency, multiple drug resistance (MDR) reversing, stimuli-responsive drug release, drug release monitoring, and enhanced particle-cell interactions. The anticancer drug doxorubicin (DOX) is efficiently loaded into this nanosystem and released in a pH-dependent manner. AmQu also effectively quenches the fluorescence of the loaded DOX, thereby allowing the use of the nanosystem for monitoring the intracellular drug release. Furthermore, a synergistic effect with the presence of AmQu is observed in both normal MCF-7 and DOX-resistant MCF-7 breast cancer cells. Due to the similar structure as dopamine, AmQu may facilitate both the interaction and internalization of PSi into the cells. Overall, this PSi-based platform exhibits remarkable superiority in both multifunctionality and anticancer efficiency, making this nanovector a promising system for anti-MDR cancer treatment.
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: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Vimalkumar
authors.initials: V
authors.lastname: Balasubramanian
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Chinmay
authors.initials: C
authors.lastname: Bhat
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Vahermo
authors.affiliation: Laboratory of Industrial Physics, Department of Physics, University of Turku, Turku, FI-20014, Finland.
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Marianna
authors.initials: M
authors.lastname: Kemell
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Flavia
authors.initials: F
authors.lastname: Fontana
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, LT-10222, Vilnius, Lithuania.
authors.forename: Agne
authors.initials: A
authors.lastname: Janoniene
authors.affiliation: Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, LT-10222, 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: Laboratory of Industrial Physics, Department of Physics, University of Turku, Turku, FI-20014, Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, 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, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.|Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.|Department of Pharmaceutical Science, Åbo Akademi University, Turku, 20520, Finland.
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: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D016062:Porosity; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D012825:Silicon / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin; D011794:Quercetin; D012825:Silicon
keywords: cellular interactions; dopamine-inspired flavonoid; multiple drug resistance; pH-sensitive; porous silicon nanoparticles