Multifunctional and High Affinity Polymer Ligand that Provides Bio-Orthogonal Coating of Quantum Dots

Abstract

We detail the design of hydrophilic metal-coordinating ligands and their use for the effective coating of luminescent quantum dots (QDs). The ligand design exploits the specific, reagent-free nucleophilic addition reaction of amine-modified molecules toward maleic anhydride to introduce several lipoic acid metal anchors, hydrophilic zwitterion moieties, and specific reactive groups along a poly(isobutylene-alt-maleic anhydride) (PIMA) chain. Tunable reactive groups tested in this study include azide, biotin, carboxyl, and amine. Cap exchange with these multilipoic acid ligands via a photochemical ligation strategy yields homogeneous QD dispersions that are colloidally stable over several biologically relevant conditions and for extended periods of time. The zwitterionic coating yields compact nanoparticle size and imparts nonsticky surface properties onto the QDs, preventing protein absorption. The introduction of a controllable number of reactive groups allows conjugation of the QDs to biomolecules via bio-orthogonal coupling chemistries including (1) attachment of the neurotransmitter dopamine to QDs via amine-isothiocyanate reaction to produce a platform capable of probing interactions with cysteine in proteins, based on charge transfer interactions; (2) self-assembly of biotinylated QDs with streptavidin-dye; and (3) ligation of azide-functionalized QDs to cyclooctyne-modified transferrin via copper-free click chemistry, used for intracellular delivery. This ligand design strategy can be used to prepare an array of metal-coordinating ligands adapted for coating other inorganic nanoparticles, including magnetic and plasmonic nanomaterials.

Detection of Rare Objects by Flow Cytometry: Imaging, Cell Sorting, and Deep Learning Approaches

“…The covalent conjugation implies the formation of covalent bonds between the target antibody and QD surface ligands. Although conventional covalent conjugation does not allow for the control over the number of conjugated proteins and their orientation, the recent advances in developing of chemoselective ligation [90,91] and bio-orthogonal [92] reactions have resulted in effective and controllable conjugation of QDs and biomolecules [93,94]. On the other hand, self-assembly based conjugation employs specific high-affinity interactions without the formation of covalent bonds.…”

Electrostatic Repulsion Controls Efficiency of Cu‐Free Click‐Reaction with Azide‐Modified Semiconductor Quantum Dots

“…Application of colloidal semiconductor quantum dots (QDs) as luminescent markers in biotechnology relies on their narrow and controllable emission band, high photoluminescence (PL) quantum yield, possibility of excitation in a wide spectral range and excellent photostability. Nowadays, modern technology allows obtaining water‐soluble colloidal semiconductor QDs with a wide variety of functional groups on the surface . One of the most important steps for practical application of QDs is their controlled conjugation with various biomolecules .…”

“…Nowadays, modern technology allows obtaining water-soluble colloidal semiconductor QDs with a wide variety of functional groups on the surface. [1][2][3][4][5][6][7][8][9] One of the most important steps for practical application of QDs is their controlled conjugation with various biomolecules. [10][11][12][13] Unlike simple molecular systems, conjugation with colloidal nanoparticles possesses some specific features, which have to be taken into consideration when choosing conjugation methods.…”

Luminomagnetic Silica-Coated Heterodimers of Core/Shell FePt/Fe3O4 and CdSe Quantum Dots as Potential Biomedical Sensor

“…These features can be improved by adequate coating procedures used to functionalize the HNS surface with organic molecules as polyethylene glycol (PEG) [21,22] and carboxymethyl dextran [23], polymers [24,25], inorganic materials like silica [26,27], and noble metals such as gold [28], among others [29,30]. Silica coating is one of the most used procedures to functionalize nanostructures for biomedical application, either as single coating layer or as intermediate coating material for this purpose, because it prevents aggregation, improves colloidal stability, decreases toxicity, and increases the biocompatible characteristics of the nanomaterials [27,31].…”