Clickable-Zwitterionic Copolymer Capped-Quantum Dots for in Vivo Fluorescence Tumor Imaging

Abstract

In the last decades, fluorescent quantum dots (QDs) have appeared as high-performance biological fluorescent nanoprobes and have been explored for a variety of biomedical optical imaging applications. However, many central challenges still exist concerning the control of the surface chemistry to ensure high biocompatibility, low toxicity, antifouling, and specific active targeting properties. Regarding in vivo applications, circulation time and clearance of the nanoprobe are also key parameters to control the design and characterization of new optical imaging agents. Herein, the complete design and characterization of a peptide-near-infrared-QD-based nanoprobe for biomedical optical imaging is presented from the synthesis of the QDs and the zwitterionic-azide copolymer ligand, enabling a bio-orthogonal coupling, till the final in vivo test through all the characterization steps. The developed nanoprobes show high fluorescence emission, controlled grafting rate, low toxicity, in vitro active specific targeting, and in vivo long circulating blood time. This is, to our knowledge, the first report characterizing the in vivo circulation kinetics and tumor accumulation of targeted zwitterionic QDs.

(Bio)conjugation Strategies Applied to Fluorescent Semiconductor Quantum Dots

“…Another example is the work of Trapiella-Alfonso et al 29 In this study, the authors proposed nanoprobes based on QDs linked to peptides employing bioorthogonal coupling through the azide-alkyne click chemistry. After transferring hydrophobic ZnCuInSe/ZnS QDs to an aqueous medium using a two-step ligand exchange methodology the authors inserted azide functions at the QDs' surface by applying zwitterionic polymers.…”

“…For that, QDs have been conjugated with a variety of molecules, such as nucleic acids, 20 antibodies and/or their fragments, 21,22 lectins 23,24 and carbohydrates. 24,25 The QDs associated with specific molecules have been applied, as fluorescent nanotools, in a great variety of studies, such as quantitative and qualitative cell labeling, 22 receptor expression and recycling investigation, 26 yeast cells labeling, 23 parasite metabolism monitoring, 27 in vivo animal applications, 28,29 cancer diagnosis and therapy. 30 In addition, several studies have been developed in the field of fluoroimmunoassays and biosensors, 1,31,32 exploiting both optical and semiconductor properties of QDs.…”

Quantum dots from microfluidics for nanomedical application

“…Another advantage of QDs is the nanoscale dimensions, which makes QDs become appropriate labels for cellular analysis and imaging. The most common labeling method of cells by QDs is nonspecific (Ma et al, ; Pons et al, ; Trapiella‐Alfonso et al, ). Cao et al () demonstrated the internalization of C‐Dots in human breast cancer cells and used near‐infrared excitation to motivate the luminescence of C‐Dots to visualize the cells.…”

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.…”