Published: April 07, 2011 r2011 American Chemical Society 1081 dx.doi.org/10.1021/bc100552p | Bioconjugate Chem. 2011, 22, 1081–1088 ARTICLE pubs.acs.org/bc Bioconjugation of Luminescent Silicon Quantum Dots for Selective Uptake by Cancer Cells Folarin Erogbogbo, †,§ Chen-An, Tien, † Ching-Wen Chang, † Ken-Tye Yong, § Wing-Cheung Law, § Hong Ding, § Indrajit Roy, † Mark T. Swihart, †,‡, * and Paras N. Prasad ‡,§, * † Department of Chemical and Biological Engineering, ‡ Department of Chemistry and § Institute for Lasers, Photonics and Biophotonics, The University at Buffalo, State University of New York Buffalo, New York 14260-4200, United States b S Supporting Information ’ INTRODUCTION Quantum dots (QDs) are semiconductor nanocrystals, 1À10 nm in diameter, that typically consist of combinations of elements from groups II and VI (CdSe, CdTe, CdS, ZnS, and ZnSe), groups IV and VI (PbS and PbSe), or groups III and V (GaAs, GaN, InP, and InAs) of the periodic table. 1,2 They are attractive for optical imaging because of their size-tunable luminescence, high photostability, brightness, and broad excitation spectra that allow QDs with multiple emission wavelengths to be excited with a single source. 3À5 By adopting techniques from drug delivery and targeted imaging technologies, heavy metal based quantum dots have been rapidly developed and investigated for many biological applications including optical imaging, 6 sentinel lymph node mapping, 7 and multiplex imaging. 8 However, translation of these well-studied quantum dots to the clinic is inhibited by toxicity concerns that stem from their incorporation of toxic heavy metals such as cadmium. 9À12 This has led to encapsula- tions strategies that create complex nanostructures with different toxicity profiles. 13 Even though extensive studies have been performed to monitor the safety of IIÀVI quantum dots, completely over- coming the toxicity concerns is not yet possible. 14À17 Thus, a re- evaluation of the fundamental materials at the core of the quantum dots is warranted. Silicon (Si) QDs may provide a breakthrough for quantum dot technology because they are based on a nontoxic element that is essential for human health, and the product of their degradation, silicic acid, can be readily excreted via the urine. 4,18,19 Even though Si QDs are attractive from a toxicity perspective, key challenges must be overcome to ensure that Si QDs can match the promise of better-studied quantum dots for biological applications. In particular, high quantum yield (QY) and long-term stability in water and biological media are essential. The surface chemistry of Si QDs is of great interest, not only because this chemistry is much different from that of heavy metal based semiconductor nanostructures, but also because the Si QD’s optical properties, which are the basis of their utility in bioimaging, strongly depend on the surface state of the particles. There have been a few reports on the synthesis and surface modification of Si QDs to improve their competitiveness with traditional quantum dots. Kortshagen’s group has produced surface-modified Si QDs with QY above 70% at near-infrared wave- lengths, for particles dispersed in organic solvents. 20 However, such high QY has not been achieved at shorter wavelengths or for Si QDs in aqueous dispersions. Sailor’s group recently developed biodegradable porous silicon for imaging tumors via the enhanced permeation and retention (EPR) effect 21 and showed that clear- ance of the material was satisfactory. The free-standing Si QDs used here and Sailor’s porous silicon particles are expected to have similar degradation routes and low toxicity from the core material. However, there are substantial differences in the chemistry, structure, and luminescence properties, to the extent that Si QDs may be considered a different nanostructure from porous silicon. To demonstrate the potential for multiphoton excitation of Si QDs, He et al. measured emission of Si QDs upon two and three photon excitation QDs, 22 while Kauzlaurich Received: December 7, 2010 Revised: March 28, 2011 ABSTRACT: Conventional quantum dots have great potential in cancer-related imaging and diagnostic applications; however, these applications are limited by concerns about the inherent toxicity of their core materials (e.g., cadmium, lead). Virtually all imaging applications require conjugation of the imaging agent to a biologically active molecule to achieve selective uptake or binding. Here, we report a study of biocompatible silicon quantum dots covalently attached to biomolecules including lysine, folate, antimesothelin, and transferrin. The particles possess desirable physical properties, surface chemistry, and optical properties. Folate- and antimesothelin-conjugated silicon quantum dots show selective uptake into Panc-1 cells. This study contributes to the preclinical evaluation of silicon quantum dots and further demonstrates their potential as an imaging agent for cancer applications.