title: Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy.
abstract: An advanced nanocomposite consisting of an encapsulated porous silicon (PSi) nanoparticle and an acid-degradable acetalated dextran (AcDX) matrix (nano-in-nano), was efficiently fabricated by a one-step microfluidic self-assembly approach. The obtained nano-in-nano PSi@AcDX composites showed improved surface smoothness, homogeneous size distribution, and considerably enhanced cytocompatibility. Furthermore, multiple drugs with different physicochemical properties have been simultaneously loaded into the nanocomposites with a ratiometric control. The release kinetics of all the payloads was predominantly controlled by the decomposition rate of the outer AcDX matrix. To facilitate the intracellular drug delivery, a nona-arginine cell-penetrating peptide (CPP) was chemically conjugated onto the surface of the nanocomposites by oxime click chemistry. Taking advantage of the significantly improved cell uptake, the proliferation of two breast cancer cell lines was markedly inhibited by the CPP-functionalized multidrug-loaded nanocomposites. Overall, this nano-in-nano PSi@polymer composite prepared by the microfluidic self-assembly approach is a universal platform for nanoparticles encapsulation and precisely controlled combination chemotherapy.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: dongfei.liu@helsinki.fi.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Department of Physics, School of Engineering and Applied Physics, Harvard University, Cambridge, 02138 MA, 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; Laboratory of Industrial Physics, Department of Physics, University of Turku, FI-20014 Turku, Finland.
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, 210029 Jiangsu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Herranz-Blanco
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Wang
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rosa
authors.affiliation: Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: António J
authors.initials: AJ
authors.lastname: Ribeiro
authors.affiliation: Department of Physics, School of Engineering and Applied Physics, Harvard University, Cambridge, 02138 MA, USA.
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: 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. Electronic address: helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D003911:Dextrans / Q000737:chemistry*; D044085:Microfluidics / Q000379:methods*; D053761:Nanocomposites / Q000737:chemistry*; D016062:Porosity; D012825:Silicon / Q000737:chemistry*
chemical_list: D003911:Dextrans; D012825:Silicon
keywords: Acetalated dextran; Combination chemotherapy; Microfluidics; Nanocomposite; Porous silicon