title: Smart Porous Silicon Nanoparticles with Polymeric Coatings for Sequential Combination Therapy.
abstract: In spite of the advances in drug delivery, the preparation of smart nanocomposites capable of precisely controlled release of multiple drugs for sequential combination therapy is still challenging. Here, a novel drug delivery nanocomposite was prepared by coating porous silicon (PSi) nanoparticles with poly(beta-amino ester) (PAE) and Pluronic F-127, respectively. Two anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately loaded into the core of PSi and the shell of F127. The nanocomposite displayed enhanced colloidal stability and good cytocompatibility. Moreover, a spatiotemporal drug release was achieved for sequential combination therapy by precisely controlling the release kinetics of the two tested drugs. The release of PTX and DOX occurred in a time-staggered manner; PTX was released much faster and earlier than DOX at pH 7.0. The grafted PAE on the external surface of PSi acted as a pH-responsive nanovalve for the site-specific release of DOX. In vitro cytotoxicity tests demonstrated that the DOX and PTX coloaded nanoparticles exhibited a better synergistic effect than the free drugs in inducing cellular apoptosis. Therefore, the present study demonstrates a promising strategy to enhance the efficiency of combination cancer therapies by precisely controlling the release kinetics of different drugs.
authors.affiliation: Department of Applied Physics, University of Eastern Finland , POB 1627, 70211 Kuopio, Finland.
authors.forename: Wujun
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmacy, University of Eastern Finland , 70211 Kuopio, Finland.
authors.forename: Rinez
authors.initials: R
authors.lastname: Thapa
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki , 00014 Helsinki, Finland.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Applied Physics, University of Eastern Finland , POB 1627, 70211 Kuopio, Finland.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Nissinen
authors.affiliation: Department of Physics and Astronomy, University of Turku , 20014 Turku, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Granroth
authors.affiliation: School of Pharmacy, University of Eastern Finland , 70211 Kuopio, Finland.
authors.forename: Ale
authors.initials: A
authors.lastname: Närvänen
authors.affiliation: Department of Chemistry, University of Eastern Finland , 80101 Joensuu, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Suvanto
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki , 00014 Helsinki, Finland.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.affiliation: Department of Applied Physics, University of Eastern Finland , POB 1627, 70211 Kuopio, Finland.
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D053761:Nanocomposites / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D012825:Silicon / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin; D017239:Paclitaxel; D012825:Silicon
keywords: combination therapy; controlled drug release; pH-responsive materials; porous silicon; surface modification; tumor microenvironment