Nanoparticle Functionalization and Its Potentials for Molecular Imaging

Abstract

Functionalization enhances the properties and characteristics of nanoparticles through surface modification, and enables them to play a major role in the field of medicine. In molecular imaging, quality functional images are required with proper differentiation which can be seen with high contrast to obtain viable information. This review article discusses how functionalization enhances molecular imaging and enables multimodal imaging by which images with combination of functions particular to each modality can be obtained. This also explains how nanoparticles interacting at molecular level, when functionalized with molecules can target the cells of interest or substances with high specificity, reducing background signal and allowing simultaneous therapies to be carried out while imaging. Functionalization allows imaging for a prolonged period and enables to track the cells over a period of time. Recent researches and progress in functionalizing the nanoparticles to specifically enhance bioimaging with different modalities and their applications are reviewed in this article.

Keywords: conjugation; functionalization; imaging; microscopy; nanoparticles.

Figure 1

Nanoparticles can be linked to various diagnostic and therapeutic molecules of interest through secondary linkers when conjugation is not possible through on‐surface reactive groups.

Figure 2

a) Confocal fluorescence microscopy images of mitochondria at 480 nm in mRoGFP HeLa cells after incubation with hexagonal A) NaYF₄:Yb³⁺/Er³⁺, B) NaYF₄:Yb³⁺/Er³⁺&SiO₂, and C) NaYF₄:Yb³⁺/Er³⁺&SiO₂‐NH₂ nanocrystals. b) Overlays of (a) and upconversion luminescence (excitation at 970 nm and detection at 500–700 nm). Adapted with permission.25 Copyright 2015, The Royal Society of Chemistry.

Figure 3

Aggregation induced emission (AIE) luminogens are fluorescent when accumulation of nanoparticles happens in tumors, which negates the false positive fluorescence and avoid confusions.

Figure 4

T1 and T2 type contrast in MR imaging. Gd(III) is usually preferred as positive contrast imaging agent. Prolonged positive contrast imaging can be done by functionalization of contrast agents to the nanoparticles. Iron oxide particles are T2 contrast agents and ultrasmall nanoparticles are dual contrast (T1/T2) agents.

Figure 5

Serial coronal PET images of 4T1 tumor‐bearing mice at different time points postinjection of a) 64Cu‐NOTA‐mSiO2‐ PEG‐TRC105, b) 64Cu‐NOTA‐mSiO2‐PEG, or c) 64Cu‐NOTA‐mSiO2‐PEG‐TRC105 with a blocking dose of TRC105. Tumors were indicated by yellow arrowheads. Adapted with permission.57 Copyright 2013, American Chemical Society.

Figure 6

Micro‐CT grayscale (upper panel) and colored (lower panel) images of A) water and B) PEGylated Au NPs. Adapted with permission.66 Copyright 2015, Elsevier.

Figure 7

a) Colorimetric detection of OTA with the naked eye, whereby grown Au NPs changed from blue to red with an increasing concentration of OTA. “Au NP only” refers to Au NPs without OTA aptamer adsorption. b) UV–vis spectra of grown Au NPs corresponding to blank (black), 0.01 × 10⁻⁹ m (blue), 1 × 10⁻⁹ m (purple), 100 × 10⁻⁹ m (green), 1 × 10⁻⁶ m (gold), and 10 × 10⁻⁶ m (orange) OTA, and Au NPs without OTA aptamer adsorption (red). c) Peak shifts of various OTA concentrations measured with respect to the peak wavelength of the blank. Error bars indicate the SD of five independent experiments. d) Mean circularity of grown Au NPs, where circularity increased as grown Au NPs became more spherical morphologically. Error bars represent the standard error for n ≥ 250 NPs. Analysis of variance (ANOVA) using the Bonferroni test with pairwise comparison; ∗P < 0.01. TEM images of grown Au NPs for e) blank, f) 10 × 10⁻⁹ m OTA, g) 10 × 10⁻⁶ m OTA, and h) Au NPs without OTA aptamer adsorption. Scale bars = 100 nm. Adapted with permission.82 Copyright 2015, American Chemical Society.

Figure 8

Amphiphilic polymer, poly‐(isobutylene‐alt‐maleic anhydride)‐functionalized near‐infrared (NIR) IR‐820 dye conjugated with iron oxide (Fe₃O₄) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR) imaging. Adapted with permission.84 Copyright 2013, American Chemical Society.

Figure 9

Image guided therapy—nanoparticles are injected intravenously into the mouse, targets the tumor cells, and get accumulated. When the mouse is exposed to radiation or specific waves, absorption at particular wavelengths causes the nanoparticles to heat up specifically to causes thermal ablation and clearance of tumor cells.