Abstract
Bovine serum albumin (BSA)-coated CdTe/ZnS quantum dots (BSA–QDs) were selected to conjugate with folic acid (FA), forming FA–BSA–QDs. This study aims to develop these small FA–BSA–QDs (less than 10 nm) for the diagnosis of cancers in which the FA receptor (FR) is overexpressed. The enhancement of cellular uptake in FR-positive human nasopharyngeal carcinoma cells (KB cells) for FA–BSA–QDs was found by means of confocal fluorescence microscopy under single-photon and two-photon excitation. The uptake enhancement for FA–BSA–QDs was further evaluated by flow-cytometric analysis in 104 KB cells, and was about 3 times higher than for BSA–QDs on average. The uptake enhancement was suppressed when KB cells had been pretreated with excess FA, reflecting that the enhancement was mediated by the association of FR at cell membranes with FA–BSA–QDs. When human embryonic kidney cells (293T) (FR-negative cells) and KB cells, respectively, were incubated with FA–BSA–QDs (1 μM) for 40 min, the FA–BSA–QD uptake by 293T cells was much weaker than that by KB cells, demonstrating that FA–BSA–QDs could undergo preferential binding on FR-positive cancer cells. These characteristics suggest that FA–BSA–QDs are potential candidates for cancer diagnosis.
Similar content being viewed by others
References
Steven DW, Arthur GW, Leslie RC, Vincent RZ, Debra SJ, Barton AK (1992) Cancer Res 52:6708–6711
John FR, Prabir KC, Manohar R (1994) Cancer 73:2432–2443
Mathias CJ, Wang S, Lee RJ, Waters DJ, Low PS, Green MA (1996) J Nucl Med 37:1003–1008
Rosenbaum SJ, Lind T, Antoch G, Bockisch A (2006) Eur Radiol 16:1054–1065
Wiener EC, Konda SD, Wang S, Brechbiel M (2002) Acad Radiol 9:S316–S319
Setua S, Menon D, Asok A, Nair S, Koyakutty M (2010) Biomaterials 31:714–729
Kennedy MD, Jallad KN, Thompson DH, Ben-Amotz D, Low PS (2003) J Biomed Opt 8:636–641
Paulos CM, Turk MJ, Breur GJ, Low PS (2004) Adv Drug Delivery Rev 56:1205–1217
Popescu MA, Toms SA (2006) Expert Rev Mol Diagn 6:879–890
Yu WW, Chang E, Drezek R, Colvin VL (2006) Biochem Biophys Res Commun 348:781–786
Manabe N, Hoshino A, Liang YQ, Goto T, Kato N, Yamamoto K (2006) IEEE Trans Nanobiosci 5:263–267
Bae PK, Kim KN, Lee SJ, Chang HJ, Lee CK, Park JK (2009) Biomaterials 30:836–842
Chen C, Peng J, Xia HS, Yang GF, Wu QS, Chen LD, Zeng LB, Zhang ZL, Pang DW, Li Y (2009) Biomaterials 30:2912–2918
Hirschey MD, Han YJ, Stucky GD, Butler A (2006) J Biol Inorg Chem 11:663–669
Nitin N, LaConte LE, Zurkiya O, Hu X, Bao G (2004) J Biol Inorg Chem 9:706–712
Masters BR, So PT, Gratton E (1997) Biophys J 72:2405–2412
Kleinfeld D, Mitra PP, Helmchen F, Denk W (1998) Proc Natl Acad Sci USA 95:15741–15746
Schroeder JE, Shweky I, Shmeeda H, Banin U, Gabizon A (2007) J Control Release 124:28–34
Pan J, Feng SS (2009) Biomaterials 30:1176–1183
Cai JL, Huang N, Zhang Y (2005) Int J Nanosci 4:229–235
Prabaharan M, Grailer JJ, Pilla S, Steeber DA, Gong S (2009) Biomaterials 30:3009–3019
Dhruba JB, Derrick WL, Harishankar J, Haridas EP, Paras NP (2005) J Am Chem Soc 127:11364–11371
Song EQ, Zhang ZL, Luo QY, Lu W, Shi YB, Pang DW (2009) Clin Chem 55:955–963
Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, Bawendi MG, Frangioni JV (2007) Nat Biotechnol 25:1165–1170
Su YY, He Y, Lu HT, Sai LM, Li QN, Li WX, Wang LH, Shen PP, Huang Q, Fan CH (2009) Biomaterials 30:19–25
Guo G, Liu W, Liang JG, He ZK, Xu HB, Yang XL (2007) Mater Lett 61:1641–1644
Derfus AM, Chan WCW, Bhatia SN (2004) Nano Lett 4:11–18
Lovrić J, Bazzi HS, Cuie Y, Fortin GR, Winnik FM, Maysinger D (2005) J Mol Med 83:377–385
Bücking W, Massadeh S, Merkulov A, Xu S, Nann T (2010) Anal Bioanal Chem 396:1087–1094
Gao X, Chan WC, Nie S (2002) J Biomed Opt 7:532–537
Yang XT, Zhang Y (2004) Langmuir 20:6071–6073
Parak WJ, Pellegrino T, Plank C (2005) Nanotechnology 16:R9–R25
Hermanson GT (1996) Bioconjugate techniques. Academic Press, San Diego, pp 173–177
Liu J, Zhu CL, Cao L, Lin L, Ge CW, Zhang TY (2009) J Cell Mol Immunol 25:875–878
Wang T, Chen JY, Zhen S, Wang PN, Wang CC, Yang WL, Peng Q (2009) J Fluoresc 19:615–621
Larson DR, Zipfel WR, Williams RM, Clark SW, Bruchez MP, Wise FW, Webb WW (2003) Science 300:1434–1436
Ma J, Chen JY, Guo J, Wang CC, Yang Wl, Xu L, Wang PN (2006) Nanotechnology 17:2083–2089
Hopt A, Neher E (2001) Biophys J 80:2029–2036
So P, Kim H, Kochevar I (1998) Opt Express 3:339–350
Acknowledgments
This work was supported by the Shanghai Municipal Science and Technology Commission (06ZR14005 and 0752nm016), the National Natural Science Foundation of China (10774027, 11074035 and 61008055), and the Shanghai Educational Development Foundation (2008CG03).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Meng, H., Chen, JY., Mi, L. et al. Conjugates of folic acids with BSA-coated quantum dots for cancer cell targeting and imaging by single-photon and two-photon excitation. J Biol Inorg Chem 16, 117–123 (2011). https://doi.org/10.1007/s00775-010-0709-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00775-010-0709-z