Enriched Au nanoclusters with mesoporous silica nanoparticles for improved fluorescence/computed tomography dual-modal imaging

Abstract

Objectives: Au nanoclusters (AuNCs) have been used widely in fluorescence bio-imaging because of their good fluorescence, small particle size and non-cytotoxicity. AuNCs are also efficient in computed tomography (CT) imaging. Hence, a dual-modal imaging probe can be constructed without any complicated modification processes by exploiting the excellent performance of AuNCs. In the present study, AuNCs were enriched with mesoporous silica nanoparticles (MSNs) to obtain enhanced fluorescence/CT dual-modal imaging, which was capable of acquiring more imaging information for diseases compared with single-mode imaging.

Materials and methods: Biocompatible bovine serum albumin (BSA)-capped AuNCs were prepared and loaded into amine-functionalized MSNs to form MSN@AuNCs. BSA-AuNCs, MSNs, and MSN@AuNCs were characterized by ultraviolet-visible (UV-vis) spectra, transmission electron microscopy (TEM), fluorescence spectra, and zeta potential. CT imaging was recorded using micro-CT scanning. Fluorescence imaging was measured using confocal laser scanning microscopy and flow cytometry.

Results: The prepared AuNCs and MSNs possessed good properties as previously reported. The fluorescence intensity and CT value of the AuNCs were enhanced after being enriched with MSNs. The nanoparticles were both non-cytotoxic. Confocal laser scanning microscopy and flow cytometry indicated that MSN@AuNCs in CAL-27 cells showed improved fluorescence imaging compared with simple AuNCs at the same concentration.

Conclusions: The results revealed that the strategy of enriching AuNCs with MSNs can obtain highly sensitive fluorescence/CT dual-modal imaging, which indicated the potential of this nanoparticle in the diagnosis and treatment of disease.

Keywords: Au nanoclusters; computed tomography; dual-modal imaging; fluorescence; mesoporous silica nanoparticles.

SCHEME 1

Schematic of enhanced fluorescence/CT dual‐modal imaging process

FIGURE 1

Characterizations of BSA‐AuNCs: A, UV‐vis absorbance spectroscopy. Inset: preparation of BSA‐AuNCs; B, 3D fluorescence spectroscopy; C, particles size; and D, TEM image. Abbreviations: bovine serum albumin (BSA), Au nanoclusters (AuNCs), ultraviolet‐visible (UV‐vis), transmission electron microscopy (TEM)

FIGURE 2

A, Schematic of MSN@AuNCs and TEM images of AuNCs, MSN and MSN@AuNCs; B, zeta potential of MSN, MSN‐NH2, AuNCs and MSN@AuNCs; C, particle size of MSN and MSN@AuNCs; D, EDX spectrum of MSN@AuNCs; and E, EDX mappings of MSN@AuNCs. Abbreviations: mesoporous silica nanoparticles (MSNs), energy dispersive X‐ray (EDX)

FIGURE 3

Characterizations of AuNCs and MSN@AuNCs: A, fluorescence emission spectra; B, photographs under daylight and UV light; C, fluorescence stability of AuNCs, MSN@AuNCs and Rhodamine; and D, fluorescence lifetime

FIGURE 4

Micro‐CT detection of AuNCs and MSN@AuNCs: (A) transverse CT images in vitro and (B) X‐ray attenuation (HU) values at various concentrations. Abbreviations: computed tomography (CT), Hounsfield Units (HU)

FIGURE 5

Cell viability of A, L929 cells, B, CAL‐27 cells, C, ACC‐2 cells and D, SCC‐25 cells exposed to AuNCs and MSN@AuNCs at various concentrations (100, 200, 400, 600 and 800 nM AuNCs) for 48 hours treatment. Data are presented as mean ± SD (n = 3). *P < .05

FIGURE 6

(A) Confocal laser scanning microscopy images and interactive 3D surface plots of CAL‐27 cells and L929 cells incubated with AuNCs and MSN@AuNCs for 6 hours; (B) average fluorescence intensity of CAL‐27 cells and L929 cells incubated with AuNCs and MSN@AuNCs for 12 and 16 hours by flow cytometry. Data are presented as mean ± SD (n = 3). *P < .05, **P < .005, ***P < .002