Cancer Cell Targeting With Functionalized Quantum Dot-Encoded Polyelectrolyte Microcapsules.

Galina Nifontova,Fernanda Ramos-Gomes,Frauke Alves,Maria Baryshnikova,Igor Nabiev,Alyona Sukhanova

doi:10.3389/fchem.2019.00034

Abstract

Imaging agents and drug carriers are commonly targeted toward cancer cell through functionalization with specific recognition molecules. Quantum dots (QDs) are fluorescent semiconductor nanocrystals whose extraordinary brightness and photostability make them attractive for direct fluorescent labeling of biomolecules or optical encoding of the membranes and cells. Here, we analyse the cytotoxicity of QD-encoded microcapsules, validate an approach to the activation of the microcapsule's surface for further functionalization with monoclonal antibody Trastuzumab, a humanized monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) and already in clinical use for the treatment of HER2 positive breast cancer. In addition, we characterize the cell-specific targeting activity of the resultant bio-conjugate by immunofluorescence assay (IFA) and real-time analysis of interaction of the conjugates with live HER2 overexpressing human breast cancer cells. We demonstrate, that encapsulation of QDs into the polymer shell using the layer-by-layer deposition method yields highly fluorescent polyelectrolyte microcapsules with a homogeneous size distribution and biocompatibility upon in vitro treatment of cancer cells. Carbodiimide surface activation ensures optimal disperse and optical characteristics of the QD-encoded microcapsules before antibody conjugation. The prepared conjugates of the microcapsules with cancer-specific monoclonal antibody targeting HER2 provide sufficiently sensitive and specific antibody-mediated binding of the microcapsules with live cancer cells, which demonstrated their potential as prospective cancer cell–targeting agents.

Highlights

Targeted micro- and nanoparticle delivery toward tumors and cancer cells is one of the major research trends in the engineering of anti-cancer theranostic and bioimaging agents
The use of Quantum dots (QDs) as an alternative to conventional, commonly used organic dyes (FITC, TRITC, RITC, etc.) for fluorescent labeling of polyelectrolyte microcapsules results in the formation of highly fluorescent microparticles ensuring their use as promising imaging tools (Gaponik et al, 2003; De Koker et al, 2007; Gao et al, 2016)
QD-encoded polyelectrolyte microcapsules were characterized by the fluorescent properties that make them promising imaging agents, as noted earlier (Nifontova et al, 2018)

Summary

Introduction

Targeted micro- and nanoparticle delivery toward tumors and cancer cells is one of the major research trends in the engineering of anti-cancer theranostic and bioimaging agents. Their controlled transportation and release of their content make it possible to reduce and mitigate off-target effects, ensuring smart delivery of drugs, and diagnostic tools (Fay and Scott, 2011; Wanakule and Roy, 2012). Polyelectrolyte microcapsules loaded with anti-cancer drugs, fluorescent dyes, and metal nanoparticles, e.g., magnetic, plasmonic, or fluorescent semiconductor nanoparticles (quantum dots, QDs), offer a promising opportunity for cancer detection and treatment (Gaponik et al, 2004; Zhao et al, 2006; Vergaro et al, 2011). Quantum dots (QD) encapsulation into the polymer shell of polyelectrolyte microcapsules is a possible way to prevent the QD toxicity for live cell and improve their biocompatibility (Romoser et al, 2011)

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Results