Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics

Abstract

Background: One of the most attractive properties of quantum dots is their potential to extend the opportunities for fluorescent and multimodal imaging in vivo. The aim of the present study was to clarify whether the composition and structure of organic coating of nanoparticles are crucial for their application in vivo. Methods: We compared quantum dots coated with non-crosslinked amino-functionalized polyamidoamine (PAMAM) dendrimers, quantum dots encapsulated in crosslinked carboxyl-functionalized PAMAM dendrimers, and silica-shelled amino-functionalized quantum dots. A multimodal fluorescent and paramagnetic quantum dot probe was also developed and analyzed. The probes were applied intravenously in anesthetized animals for visualization of brain vasculature using two-photon excited fluorescent microscopy and visualization of tumors using fluorescent IVIS ® imaging (Caliper Life Sciences, Hopkinton, MA) and magnetic resonance imaging. Results: Quantum dots coated with non-crosslinked dendrimers were cytotoxic. They induced side effects in vivo, including vasodilatation with a decrease in mean arterial blood pressure and heart rate. The quantum dots penetrated the vessels, which caused the quality of fluorescent imaging to deteriorate. Quantum dots encapsulated in crosslinked dendrimers had low cytotoxicity and were biocompatible. In concentrations <0.3 nmol quantum dots/kg bodyweight, these nanoparticles did not affect blood pressure and heart rate, and did not induce vasodilatation or vasoconstriction. PEGylation (PEG [polyethylene glycol]) was an indispensable step in development of a quantum dot probe for in vivo imaging, based on silica-shelled quantum dots. The non-PEGylated silica-shelled quantum dots possessed low colloidal stability in high-salt physiological fluids, accompanied by rapid aggregation in vivo. The conjugation of silica-shelled quantum dots with PEG1100 increased their stability and half-life in the circulation without significant enhancement of their size. In concentrations <2.5 nmol/kg bodyweight, these quantum dots did not affect the main physiological variables. It was possible to visualize capillaries, which makes this quantum dot probe appropriate for investigation of mediators of vasoconstriction, vasodilatation, and brain circulation in intact animals in vivo. The multimodal silica-shelled quantum dots allowed visualization of tumor tissue in an early stage of its development, using magnetic resonance imaging. Conclusion: The present study shows that the type and structure of organic/bioorganic shells of quantum dots determine their biocompatibility and are crucial for their application in imaging in vivo, due to the effects of the shell on the following properties: colloidal stability, solubility in physiological fluids, influence of the basic physiological parameters, and cytotoxicity.

Dendrimer-based magnetic resonance imaging agents for brain cancer

“…. . [140], rhodamine [92,93], quantum dots [141], etc, for more accurate and sensitive multi-modal imaging [41]. Often, fluorescent imaging enables the precise delineation of tumor margins and hence more complete resection of the tumor during surgery.…”

Quantum dots as a platform for nanoparticle drug delivery vehicle design

“…As virtually all nano-sized particles are recognized as foreign objects by the body’s defense and accumulate within MPS-containing organs [135], optimization of surface coatings, which provide an interface and define interactions between the NP core and the environment, becomes of critical importance. In realizing this opportunity, QDots have already demonstrated utility for nanocarrier biodistribution studies as sole imaging agents (when combined with whole-body fluorescence imaging, intravital microscopy, and post-mortem evaluation of tissues and organs [97, 136, 137]) or in combination with other tracers ( e.g. labels for positron emission tomography and scintigraphic imaging [138, 139]).…”

Subnano Surface Engineering of TiO2 Nanoparticles by PET Molecular Layer Deposition: Tuning Photoactivity and Dispersibility

“…Organic coatings are of interest due to the advantages they hold over their inorganic analogues, such as biocompatibility (5,6), lower raw material costs, and reduced environmental impact (7). In industry, the biocompatibility of polymeric films is of particular interest to the cosmetics sector (8,9), and promises applicability to nanomedicine (10). Organic coatings also provide the opportunity to improve particle dispersibility in organic media (11,12), potentially enhancing the performance of organic-based paints, nanofluids (13), Pickering emulsions (14), and polymer nanocomposites (15).…”