RESEARCH PAPER Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates John J. Castillo • Tomas Rindzevicius • Kaiyu Wu • Michael S. Schmidt • Katarzyna A. Janik • Anja Boisen • Winnie Svendsen • Noemi Rozlosnik • Jaime Castillo-Leo ´n Received: 13 March 2014 / Accepted: 16 June 2014 Ó Springer Science+Business Media Dordrecht 2014 Abstract Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through cou- pling of amine groups of PNTs and carboxylic groups of FA. The surface analysis of PNT-FA indicated the presence of FA aggregates on the surface of PNTs. The covalent interaction between FA and self-assembled PNTs was further investigated using fluorescence microscopy, Raman and surface-enhanced Raman scattering (SERS) spectroscopies. The SERS experi- ments were performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthe- sis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors. Keywords Peptide nanotubes Á Folic acid Á Assembly Á SERS Á Drug delivery Á Biomedicine Introduction In recent years, there has been an increasing interest in the fabrication of new nanoscale material assemblies for diagnostics and treatment of a variety of diseases (Yan et al. 2010; Petrov and Audette 2012; Doll et al. 2013). A special attention has been directed toward nontoxic, chemically stable and biocompatible nanomaterials such as self-assembled peptide nano- tubes (PNTs) (Scanlon and Aggeli 2008). PNTs are biological species that are able to self-organize rapidly under mild conditions without employing specialized equipment or high temperatures (Scanlon and Aggeli 2008), and they display an exceptional functional diversity (Gazit 2007; Davies 2006) and nontoxicity (Seabra and Duran 2013). The latter is a noteworthy issue in carbon nanosystems (Doll et al. 2013), and it is Electronic supplementary material The online version of this article (doi:10.1007/s11051-014-2525-9) contains supple- mentary material, which is available to authorized users. J. J. Castillo (&) Á T. Rindzevicius Á K. Wu Á M. S. Schmidt Á A. Boisen Á W. Svendsen Á N. Rozlosnik Á J. Castillo-Leo ´n Department of Micro and Nanotechnology, Technical University of Denmark, 2800 Lyngby, Denmark e-mail: jjcl@nanotech.dtu.dk J. J. Castillo Universidad Industrial de Santander, Bucaramanga, Colombia K. A. Janik Center for Electron Nanoscopy, Technical University of Denmark, Lyngby, Denmark 123 J Nanopart Res (2014) 16:2525 DOI 10.1007/s11051-014-2525-9