Peptide-Conjugated Quantum Dots Activate Neuronal Receptors and

Peptide-Conjugated Quantum Dots Activate Neuronal Receptors and Initiate ... of downstream of receptor signaling cascades and resulting modulation of ...
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Peptide-Conjugated Quantum Dots Activate Neuronal Receptors and Initiate Downstream Signaling of Neurite Growth

2005 Vol. 5, No. 4 603-607

Tania Q. Vu,*,† Ravikanth Maddipati,‡ Todd A. Blute,§ Barrett J. Nehilla,| Leora Nusblat,† and Tejal A. Desai*,† Department of Biomedical Engineering, 44 Cummington St., Room 701, Boston UniVersity, Boston, Massachusetts 02215, Boston UniVersity School of Medicine, 715 Albany Street, Box 86, Boston, Massachusetts 02118, Department of Biology, 5 Cummington St., Boston UniVersity, Boston, Massachusetts 02215, and Department of Pharmacology and Experimental Therapeutics, Boston UniVersity, Boston, Massachusetts 02118 Received December 6, 2004; Revised Manuscript Received February 8, 2005

ABSTRACT Quantum dots (QDs) could serve as fluorescent scaffolds for effecting specific physiological and pharmacological responses in cells. Here, we conjugate the peptide ligand βNGF to QD surfaces, and confirm surface modification and single QD nanostructure using AFM. We show that βNGF-QDs retain bioactivity, activate TrkA receptors, and initiate neuronal differentiation in PC12 cells. Receptor-evoked activity of QDimmobilized ligands has wide-ranging implications for the development of molecular tools and therapeutics targeted at understanding and regulating cell function.

Semiconductor quantum dots (QDs) offer exciting potential as fluorescent nanoscale platforms for probing biomolecular interactions in living cells. QDs exhibit unique optical properties including extended photostability and multicolor excitation, and a growing body of work indicates their applicability as novel fluorophores for biological imaging.1-4 As nanoparticles, QDs possess controllable surface properties, are comparable to the size of proteins (5-15 nm), and thus could serve to deliver biomolecules and other exogenous drug compounds to cellular targets. Presently, a majority of QD biological applications employ surface-immobilized antibodies and in some cases, peptides, to passively bind and recognize the location of subcellular targets.5 A less developed area of study is the immobilization of ligands and other effector compounds to the QD surface to evoke specific cell physiological and pharmacological responses. While examples of ligand-immobilized glass, agarose, polymer, and other surfaces exist, the biological effects of these covalently bonded hormones, drugs, and transmitter ligands have not * Corresponding authors. Phone: 617-358-2832; Fax: 617-358-2835; E-mail: [email protected], [email protected]. † Department of Biomedical Engineering, Boston University. ‡ Boston University School of Medicine. § Department of Biology, Boston University. | Department of Pharmacology and Experimental Therapeutics, Boston University. 10.1021/nl047977c CCC: $30.25 Published on Web 03/24/2005

© 2005 American Chemical Society

been well substantiated.6 Furthermore, past work has focused on macroscopic surfaces, and little is known concerning the biological interactions of ligand-immobilized nanoscale entities (