title: Multidentate Polymer Coatings for Compact and Homogeneous Quantum Dots with Efficient Bioconjugation.
abstract: Quantum dots are fluorescent nanoparticles used to detect and image proteins and nucleic acids. Compared with organic dyes and fluorescent proteins, these nanocrystals have enhanced brightness, photostability, and wavelength tunability, but their larger size limits their use. Recently, multidentate polymer coatings have yielded stable quantum dots with small hydrodynamic dimensions (≤10 nm) due to high-affinity, compact wrapping around the nanocrystal. However, this coating technology has not been widely adopted because the resulting particles are frequently heterogeneous and clustered, and conjugation to biological molecules is difficult to control. In this article we develop new polymeric ligands and optimize coating and bioconjugation methodologies for core/shell CdSe/Cd(x)Zn(1-x)S quantum dots to generate homogeneous and compact products. We demonstrate that "ligand stripping" to rapidly displace nonpolar ligands with hydroxide ions allows homogeneous assembly with multidentate polymers at high temperature. The resulting aqueous nanocrystals are 7-12 nm in hydrodynamic diameter, have quantum yields similar to those in organic solvents, and strongly resist nonspecific interactions due to short oligoethylene glycol surfaces. Compared with a host of other methods, this technique is superior for eliminating small aggregates identified through chromatographic and single-molecule analysis. We also demonstrate high-efficiency bioconjugation through azide-alkyne click chemistry and self-assembly with hexa-histidine-tagged proteins that eliminate the need for product purification. The conjugates retain specificity of the attached biomolecules and are exceptional probes for immunofluorescence and single-molecule dynamic imaging. These results are expected to enable broad utilization of compact, biofunctional quantum dots for studying crowded macromolecular environments such as the neuronal synapse and cellular cytoplasm.
authors: Liang
authors: L
authors: Ma
authors: School of Physical Science and Technology, ShanghaiTech University , 100 Haike Rd., Pudong New Area, Shanghai, 201210, China.
authors: Chunlai
authors: C
authors: Tu
authors: Phuong
authors: P
authors: Le
authors: Shweta
authors: S
authors: Chitoor
authors: Sung Jun
authors: SJ
authors: Lim
authors: Mohammad U
authors: MU
authors: Zahid
authors: Kai Wen
authors: KW
authors: Teng
authors: Pinghua
authors: P
authors: Ge
authors: Paul R
authors: PR
authors: Selvin
authors: Andrew M
authors: AM
authors: Smith
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000180:Acrylic Resins / Q000737:chemistry*; D015374:Biosensing Techniques / Q000379:methods*; D019187:Cadmium Compounds / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D066246:ErbB Receptors / Q000737:chemistry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry; D008024:Ligands; D045663:Quantum Dots / Q000737:chemistry*; D018036:Selenium Compounds / Q000737:chemistry; D013388:Succinimides / Q000737:chemistry*; D000099166:Polyacrylamides
chemical_list: D000179:Acrylates; D000180:Acrylic Resins; D019187:Cadmium Compounds; D004247:DNA; D066246:ErbB Receptors; D018796:Immunoconjugates; D008024:Ligands; D018036:Selenium Compounds; D013388:Succinimides; D000099166:Polyacrylamides; C515393:N,N-acryloyloxysuccinimide; C058667:cadmium selenide; C512478:EGFR protein, human; C001426:N-hydroxysuccinimide