Au CdHg Te quantum dots for in vivo tumor-targeted

ORIGINAL PAPER

Au:CdHgTe quantum dots for in vivo tumor-targeted multispectral fluorescence imaging

Sihai Han &Ying Mu &Qiangyuan Zhu &Yibo Gao &Zuhong Li &Qinhan Jin &Wei Jin

Received:31December 2011/Revised:24February 2012/Accepted:29February 2012/Published online:25March 2012#Springer-Verlag 2012

Abstract Near-infrared gold-doped CdHgTe quantum dots (QDs)with improved photoluminescence and biocompatibil-ity were developed using an aqueous solution route with L -glutathione and L -cysteine as stabilizers.As-prepared Au:CdHgTe QDs were covalently linked to arginine –glycine –aspartic acid (RGD)peptide,anti-epidermal growth factor receptor (EGFR)monoclonal antibody (MAb),and anti-car-cinoembryonic antigen-related cell adhesion molecule-1(CEACAM1)MAb separately.Three Au:CdHgTe QD bio-conjugates (QD800-RGD,QD820-anti-CEACAM1,and QD840-anti-EGFR)were successfully used as probes for in vivo tumor-targeted multispectral fluorescence imaging of xenografts.Fluorescence signals from the QD bioconjugates used to detect three tumor markers were spectrally unmixed,and their co-localization was analyzed.The results indicate that multiple tumor markers could be simultaneously detected by multispectral fluorescence imaging in vivo using QD bio-conjugates as probes.This approach has excellent potential as an imaging method for the noninvasive exploration and de-tection of multiple tumor markers in vivo,thereby substan-tially aiding the diagnosis of cancer.

Keywords Au:CdHgTe .Quantum dots .Tumor .Multispectral .Fluorescence .Imaging

Introduction

Multispectral fluorescence imaging (MSFI),which captures fluorescence image data at specific spectral frequencies,is attracting extensive interest in the fields of biomedical imag-ing and nanotechnology applications [1].MSFI in vivo is also a promising technique for sensitive detection of cancer [2].In traditional fluorescence imaging in vivo,an important limiting factor is that the emission spectra of fluorescent labels of biological interest would overlap significantly,and these fluo-rescent signals may also be obscured by autofluorescence of the animal.MSFI offers a unique solution to this problem by utilizing full imaging over a wide range of optical frequencies and spectral unmixing algorithms,and could simultaneously detect multiple types of tumor markers in vivo,potentially leading to improved accuracy of cancer diagnosis.

Fluorescent probes with good optical properties play an important role in MSFI.Quantum dots (QDs)are semicon-ductor nanocrystals characterized by size-and composition-dependent optical properties such as high levels of bright-ness and photostability,broad excitation spectra,and narrow emission bands [3].Moreover,multiple emission spectra of several different QDs can be simultaneously excited with a single excitation wavelength [4].These features make QDs the ideal candidate for MSFI.Among the QDs,near-infrared (NIR)QDs are particularly suitable for in vivo fluorescence imaging,because most biological tissues absorb compara-tively weakly in the NIR spectral range (650–900nm).So far,many NIR fluorescent QDs have been developed,such as CdHgTe [5,6],CdTe/CdSe [7],CdTe 1−x Se x /CdS [8],InAs/InP/ZnSe [9],InAs x P 1−x /InP/ZnSe [10],CdTe x Se 1−x /CdS [11],CuInSe [12],Cu:InP/ZnSe [13],Hg x Cd 1−x Te/CdTe /Cd x Zn 1−x S [14],and Cd 3As 2[15]QDs.Although some func-tionalized NIR QDs have been used for in vivo imaging

S.Han :Y .Mu (*):Q.Zhu :Y .Gao :Z.Li :Q.Jin :W.Jin (*)Research Center for Analytical Instrumentation,

Institute of Cyber-Systems and Control,State Key Lab.of Industrial Control Technology,Zhejiang University,Hangzhou 310058,China e-mail:muying@ e-mail:jinweimy@

Anal Bioanal Chem (2012)403:1343–1352DOI 10.1007/s00216-012-5921-y