Functionalization of Alkyne-Terminated Thermally Hydrocarbonized Porous Silicon Nanoparticles With Targeting Peptides and Antifouling Polymers: Effect on the Human Plasma Protein Adsorption Chang-Fang Wang,* ,† Ermei M. Ma ̈ kila ̈ , †,§ Colin Bonduelle, ‡ Jussi Rytkö nen, ∥ Janne Raula, ⊥ Se ́ rgio Almeida, † Ale Na ̈ rva ̈ nen, ∥ Jarno J. Salonen, § Sebastien Lecommandoux, ‡,¶ Jouni T. Hirvonen, † and He ́ lder A. Santos* ,† † Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland § Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland ‡ Universite ́ de Bordeaux/IPB, ENSCBP, 16 Avenue Pey Berland, 33607, Pessac Cedex, France ∥ School of Pharmacy, University of Eastern Finland, FI-70211 Kuopio, Finland ⊥ Department of Applied Physics, Aalto University School of Science, P.O. Box 15100, FIN-00076 Aalto, Espoo, Finland ¶ CNRS, Laboratoire de Chimie des Polymeres Organiques (UMR5629), 33607 Pessac Cedex, France * S Supporting Information ABSTRACT: Porous silicon (PSi) nanomaterials combine a high drug loading capacity and tunable surface chemistry with various surface modifications to meet the requirements for biomedical applications. In this work, alkyne-terminated thermally hydrocarbonized porous silicon (THCPSi) nanoparticles were fabricated and postmodified using five bioactive molecules (targeting peptides and antifouling polymers) via a single-step click chemistry to modulate the bioactivity of the THCPSi nanoparticles, such as enhancing the cellular uptake and reducing the plasma protein association. The size of the nanoparticles after modification was increased from 176 to 180−220 nm. Dextran 40 kDa modified THCPSi nanoparticles showed the highest stability in aqueous buffer. Both peptide- and polymer-functionalized THCPSi nanoparticles showed an extensive cellular uptake which was dependent on the functionalized moieties presented on the surface of the nanoparticles. The plasma protein adsorption study showed that the surface modification with different peptides or polymers induced different protein association profiles. Dextran 40 kDa functionalized THCPSi nanoparticles presented the least protein association. Overall, these results demonstrate that the “click” conjugation of the biomolecules onto the alkyne-terminated THCPSi nanoparticles is a versatile and simple approach to modulate the surface chemistry, which has high potential for biomedical applications. KEYWORDS: surface modification, porous silicon, cell−nanoparticle interaction, click chemistry, protein adsorption 1. INTRODUCTION Nanomedicine has been intensively investigated for healthcare applications during the past decades. The aim of nanomedicine is to develop more efficient and low side effect drug delivery systems. Many nanosystems have already shown promising preclinical 1−3 and clinical results. 2,4−6 Porous silicon (PSi) nanoparticles have a number of unique properties that render them as a potential drug delivery nanovehicle, such as increasing the dissolution rate of poorly water-soluble drugs, 7 high drug loading capacity, 8 and control- lable surface structure for further modification to meet the biomedical application requirements. 1,9−12 The native Si−H x (x =1−4) terminated PSi surface is highly reactive and prone to spontaneous oxidation in the air. 13 Surface passivation via hydrosilylation, thermal oxidation, thermal carbonization, or thermal hydrocarbonization has been used to stabilize the PSi surface. 8,14 By using different stabilization methods, the hydrophilicity and resistance to degradation of the PSi Received: November 8, 2014 Accepted: December 25, 2014 Published: December 25, 2014 Research Article www.acsami.org © 2014 American Chemical Society 2006 DOI: 10.1021/am507827n ACS Appl. Mater. Interfaces 2015, 7, 2006−2015