Gold Nanoclusters‐Based Nanoprobes for Simultaneous Fluorescence Imaging and Targeted Photodynamic Therapy with Superior Penetration and Retention Behavior in Tumors

Abstract

Gold nanoclusters (GNCs) attract increasing attention due to their potential applications in sensing, catalysis, optoelectronics, and biomedicine. Herein, the formation of highly fluorescent glutathione (GSH)‐capped GNCs is achieved through the delicate control of the reduction kinetics and thermodynamic selection of the Au(I)–SG complexes. Furthermore, the GNCs‐based nanoprobes are developed by the covalent coupling folic acid (FA) and PEG (polyethylene glycol) on the surface of GNCs directly, followed by trapping photosensitizer (chlorin e6, Ce6) within PEG networks and attaching to the GNCs surface. The fabricated nanoprobes (Ce6@GNCs‐PEG2K‐FA) possess a uniform particle size (hydrodynamic diameter ≈6.1 ± 1.2 nm), without affecting the yield of singlet oxygen of the trapped Ce6. In vitro studies show the enhanced cellular uptake and satisfactory photodynamic therapy (PDT) effectiveness toward MGC‐803 cells when compared with free Ce6. The biodistribution and excretion pathway studies of the nanoprobes in MGC‐803 tumor‐bearing nude mice reveal their superior penetration and retention behavior in tumors, while the preserved features of renal clearance and stealthy to reticulo‐endothelial system are mainly attributed to the small hydrodynamic diameters and the FA‐capped PEGylated ligands. The enhanced PDT efficacy and the nontoxicity to mice provide an exciting new nano‐platform with promising clinical translational potential.

Zwitterion functionalized gold nanoclusters for multimodal near infrared fluorescence and photoacoustic imaging

“…Those metal NCs, mainly gold, are made of ten to hundred atoms and usually presented as species filling the gap between molecules and nanoparticles. [1][2][3][4] Gold nanoclusters (Au NCs) present several features making them appealing for cancer therapy thanks to (i) their high renal clearance 5,6 reducing toxicity risk, (ii) the relatively high tumor retention by passive uptake, 7,8 (iii) the ability to trigger cell death under light illumination 9 or radiosensitization, [10][11][12] and (iv) the detection by multimodal imaging techniques. [13][14][15] In optical imaging, one of the great advantages of Au NCs compared to plasmonic Au nanoparticles (Au NPs) is related to the ability to visualize them by fluorescence in the red-near-infrared (NIR) region (650-800 nm), a spectral window suitable for in vivo studies due to the reduced tissue scattering and low blood absorption.…”

In vivo high-efficiency targeted photodynamic therapy of ultra-small Fe3O4@polymer-NPO/PEG-Glc@Ce6 nanoprobes based on small size effect

“…By comparison with free Ce6 (641 nm), the UV-Vis spectroscopy also indicated that there was a significant bathochromic shift in the region of the Ce6 Q(I) band of nanoprobe-4 nm (665 nm), nanoprobe-8 nm (673 nm) and nanoprobe-13 nm (660 nm), which is a typical characteristic of Ce6 in different chemical environments. 8 The results indicated that free Ce6 was successfully encapsulated by the NPO. Interestingly, the characteristic peak intensity of the three types of nanoprobes (700 nm) in the region of the Ce6 Q (II) band was markedly higher than that of free Ce6.…”

“…8 To confirm the phototoxicity of the three types of Fe 3 O 4 @P-NPO/PEG-Glc@Ce6 nanoprobes, the standard DCFH-DA staining protocol was carried out to evaluate their ability to generate intracellular singlet oxygen. As shown in Figure 6a, without the laser, the synthesized nanoprobes produced singlet oxygen with a similar ability, slightly more than free Ce6.…”

“…To date, many nanoplatforms, such as gold nanoclusters, 7,8 carbon nanomaterials, 9,10 quantum dots 11 and upconversion nanomaterials 12,13 have been explored as the carriers of photosensitizers for PDT. However, medical translation of the traditional nanoplatforms has been hindered owing to the high toxicity and low efficiency of PDT.…”

The Excretion of BRCAA Antibody-Conjugated Gold Nanoclusters from Kidneys of Treated Rats

“…Au-NCs have attracted more attention in the past decade because of their ultra small size, excellent luminescence properties and stable structures or good storage stability [11][12][13][14]. In the recent years, gold nanoparticles have emerged for delivery of various payloads into their targets [15][16][17][18][19][20]. The payloads include small molecule drugs and big molecular proteins such as antibody and peptide.…”