Table 1.
A summary of studies on the in vivo use of gold nanocomplexes in systemic cancer imaging
| Functional ligand | Cancer type | In vivo model | Imaging technique | Comment | Reference |
|---|---|---|---|---|---|
| Gold nanospheres | |||||
| Stabilizing ligand: PEG and PEI Targeting ligand: FA |
Papilloma (KB cells) | S.C. xenograft mouse | CT | The AuNP-PEI was modified with FA-linked PEG, forming FA-targeted PEGylated AuNPs. The resultant targeted AuNPs presented potential role as a nanoprobe for CT imaging of FA receptor-overexpressing xenografted tumor | 77 |
| Stabilizing ligand: PEG fluorescent dye | Colon carcinoma (CT26 cells) | S.C. allograft mouse | CT | The signal intensity and nanoprobe accumulation of Au-NPAPF-PEG in the tumor were up to 24 h post i.v. injection, suggesting the role as a promising nanoprobe for in vivo tumor-targeted CT imaging | 87 |
| Stabilizing ligands: PEG and glucose Targeting ligand: glucose |
Melanoma (SKMEL23 cells) | S.C. xenograft mouse | CT | The AuNP-labeled T cells were injected intravenously to mice-bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T cells | 88 |
| Stabilizing ligand: PEG | Lung cancer (SPC- A1 cells) | S.C. xenograft mouse | CT | Results suggest that PEGylated AuNPs can be used as a promising contrast agent with enhanced biocompatibility for CT imaging in cancer diagnosis | 89 |
| Hybrid formulation: mesoporous silica NPs emitter: 64Cu |
Lung cancer | Urethane- induced lung cancer mouse | PET | 64Cu-labeled gold/mesoporous silica hybrid NPs can successfully detect the existence of clinically relevant spontaneous lung tumors in a urethane-induced lung cancer mouse model through PET imaging | 90 |
| Stabilizing ligand: PEG Targeting ligand: TAT Emitter: Gd3+ |
Glioblastoma (U87 cells) | Orthotopic xenograft mouse | MRI | Compared with the Gd3+ chelate, TAT-Au NP-Gd conjugates showed a 2.2-fold higher relaxivity and 82-fold enhancement in Gd3+ cellular uptake, which allowed for sensitive detection of the cancer cells via MRI | 91 |
| Stabilizing ligand: PEG Targeting ligand: RGD Emitter: 125I |
Glioblastoma (U87 MG cells) | S.C. xenograft mouse | SPECT/CT | In vivo SPECT/CT imaging results showed that the 125I-labeled RGD-PEG-AuNP probes can target the tumor site as soon as 10 min after injection | 92 |
| Stabilizing ligand: PEG Targeting ligand: DAPTA |
TNBC (4T1 cells) | Orthotopic allograft mouse | SPECT/CT | The synthesis of AuNPs was doped with 199Au atoms into the crystal lattice of each AuNP, which ensured the highest possible stability for the radiolabel. When conjugated with DAPTA for the CCR5 receptor, the targeted AuNPs resulted in the in vivo sensitive and specific detection | 84 |
| Stabilizing ligand: GC MMP sensitive linker: MMP peptide NIR dye: Cy5.5 |
Colorectal cancer (HT-29 cells) | S.C. xenograft mouse | CT NIR fluorescence imaging |
The quenched Cy5.5 was recovered by cleavage of the peptide substrates upon exposure to the active MMPs, which is overexpressed in tumor tissue. As a result, the AuNPs simultaneously provided CT images with high spatial resolution and optical images with high sensitivity | 93 |
| Stabilizing ligand: PEG Targeting ligand: FA Emitter: Gd3+ |
Papilloma (KB cells) | S.C. xenograft mouse | CT MRI |
With the modification of PEG and the FA- targeting ligand, the multifunctional AuNPs were able to be used for dual-mode CT/MRI of xenograft tumor models overexpressing FA receptors | 94 |
| Photostability enhancer: PB | Colon adenocarcinoma (HT-29 cells) | S.C. xenograft mouse | PAI CT |
The AuNPs were coated with PB to form the core/shell Au@PB NPs, which were found to be an excellent photoabsorbing agent for both PTT and PAI. The gold core ensured a remarkable contrast enhancement for CT imaging | 95 |
| Stabilizing ligand: PEG NIR dye: Cy5.5 | Squamous carcinoma (SCC7 cells) | S.C. allograft mouse | PAI NIR fluorescence imaging |
The resultant AuNPs showed high fluorescence and PAI signals in the tumor over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.64±0.5I for optical imaging and 2.5±0.27 for PAI) | 96 |
| GNRs | |||||
| Stabilizing ligand: PEG Targeting ligand: biotin |
Squamous carcinoma (SCC7 cells) | S.C. allograft mouse | PAI | Under the photothermal/photoacoustic imaging, the in vivo pharmacodynamic effect of resultant GNRs could be monitored by precisely controlling the irradiation time and intensity of the NIR light | 97 |
| Amphiphilic ligands: PEG and PLGA | Glioblastoma (U87 MG cells) | S.C. xenograft mouse | PAI | Amphiphilic AuNRs were prepared by grafting with PEG and PLGA forming vesicles. Enhanced PA signals were due to the strong plasmonic coupling of the gold in the vesicular shell | 73 |
| Stabilizing ligand: PEG Targeting ligand: CET |
Epithelial carcinoma (A431 cells) | S.C. xenograft mouse | NIR fluorescence imaging | The NIR absorption images showed that the relative total photon counts from targeted Au nanorods in tumor tissue at 6 h were 10-fold higher than those from nontargeted counterparts | 68 |
| Stabilizing ligand: PEG NIR dye and photosensitizer: AlPcS4 |
Squamous carcinoma (SCC7 cells) | S.C. xenograft mouse | NIR fluorescence imaging | After i.v. injection of the AuNP-AlPcS4 complex, tumor sites were clearly identified on NIR fluorescence imaging as early as 1 h after injection | 98 |
| Stabilizing ligand: PNIPAAmMA MRI contrast agents: Fe3O4 NPs |
Glioma (C6 cells) | S.C. xenograft mouse | PET PAI |
GNRs were coated with PNIPAAmMA and Fe3O4 NPs using a simple LbL method, demonstrating the accurate tumor location using dual MRI and PAI | 99 |
| Stabilizing ligand: PEG SERS reporters | Ovarian cancer (MDA-435S, HEY, SKOv3 cells) | S.C. xenograft mouse | PAI SERS imaging |
PEGylated Au nanorods allowed presurgical PAI visualization of a tumor for locoregional staging as well as intraoperative SERS imaging for complete resection of tumor margins | 100 |
| Stabilizing ligand: liposome | Liver cancer (HepG2, Huh-7) | Orthotopic xenograft mouse | PAI NIR fluorescence imaging |
ICG-loaded liposome-Au nanorods exhibit favorable biocompatibility, high stability, and enhanced dual-model imaging signal | 101 |
| Gold nanoshells | |||||
| Stabilizing ligand: PPAA shell Targeting ligand: CET Emitter:89Zr |
Epithelial carcinoma (A431 cells) | S.C. xenograft mouse | PET | PET studies showed that the resultant AuNPs-PPAA-CET-89Zr provided high tumor- to-background ratio, suggesting a valuable tool for theranostic purposes | 102 |
| Stabilizing ligand: PEG Emitter: 64Cu |
Head and neck squamous cell carcinoma (SCC4 cells) | S.C. xenograft rat | PET/CT | The in vivo distribution of 64Cu-Au nanoshells was monitored using PET/CT imaging at various time points after i.v. injection | 103 |
| Targeting ligand: lectin MRI contrast agents: Fe3O4NPs |
Colorectal cancer (Sw620 cells) | S.C. xenograft mouse | MRI CT |
The lectin-Fe2O3@Au nanoshells showed great potential for dual-mode MRI and CT imaging of colorectal cancer in vivo | 85 |
| Targeting ligand: antibody (anti-NGAL) MRI contrast agents: Fe3O4NPs |
Pancreatic cancer (AsPC-1 cells) | S.C. xenograft mouse | MRI NIR fluorescence imaging |
Antibody-conjugated Au nanoshells specifically targeted pancreatic cancer cells in vivo providing contrast for both NIR fluorescence and T2-weighted MRI with high tumor contrast | 104 |
| Stabilizing ligand: PEG Emitter: Gd3+ |
Melanoma (B16- F10 cells) | S.C. xenograft mouse | MRI X-ray imaging Optical imaging |
The Gd3+-conjugated Au-silica nanoshells showed great potential for multimode MRI, X-ray imaging, and optical imaging of melanoma in vivo | 105 |
| MMP-triggering ligand: gelatin MRI contrast agent:Fe3O4 |
Hepatoma (H22 cells) | S.C. allograft mouse | CT and PAT imaging and MRI | A bio-eliminable MPNA, assembled from Fe3O4 nanocluster and gold nanoshell, could respond to the local microenvironment with acidic pH and enzymes in tumors, collapse into small molecules and discrete NPs, and finally be cleared from the body | 106 |
| Gold nanoclusters | |||||
| Stabilizing ligand: BSA Targeting ligand: methionine NIR dye: hydrophilic ICG |
Breast cancer (MDA-MB-231 cells) | S.C. xenograft mouse | NIR fluorescence imaging | The fluorescence signal in receptor-positive tumor was distinguishable from the normal tissues at 2 h post injection, reached peak intensity at 10 h post injection, and was still detectable at 96 h | 107 |
| Stabilizing ligand: BSA Targeting ligand: FA and HA |
Liver cancer (HepG2 cells) Adenocarcinoma (A549 cells) | S.C. xenograft mouse | NIR fluorescence imaging | The strong fluorescence was observed at the tumor sites derived from the selectively accumulated targeted AuNPs, demonstrating a promising probe for the cancer diagnosis | 108 |
| Stabilizing ligand: BSA Nuclear imaging moiety: Hoechst |
Pancreatic tumor (MiaPaca-2 cells) | S.C. xenograft mouse | Maestro™ 2 in vivo imaging system | The in vivo imaging was performed via blue and red channels which displayed the accumulation of Hoechst-AuNCs mainly in the tumor and partly in the liver and kidneys | 109 |
| Stabilizing ligand: PEG Emitter: 64Cu |
Prostate cancer (PC3 cells) | S.C. xenograft mouse | PET/CT | PET/CT results demonstrated the heterogeneous intratumoral distribution of 64CuAuNCs-PEG350 and 64CuAuNCs-PEG1000 | 110 |
| Emitter: 64Cu | Glioblastoma (U87 MG cells) | S.C. xenograft mouse | PET IvIS® imaging system |
64Cu-dopped AuNCs showed satisfactory synergistic dual-modality PET and self- illuminating NIR tumor imaging | 111 |
| Stabilizing ligand: BSA Emitter: Gd3+ |
Breast cancer (MCF-7 cells) | S.C. xenograft mouse | CT NIR fluorescence imaging MRI |
The hybrid gold-gadolinium nanoclusters provided a promising nanoprobe for cancer- targeted imaging and diagnosis in vivo | 112 |
| Stabilizing ligand: hairpin-DNA | Melanoma (M14 cells) | S.C. xenograft mouse | NIR fluorescence imaging | The hairpin-DNA-modified NaYF4@SiO4-Au promoted simultaneous deep tissue imaging and drug molecule release when combining single-band anti-stokes NIR emission and the photothermal effect | 113 |
| pH-sensitive ligand: azide and alkyne functionalities | Glioma (U87MG cells) | Orthotopic xenograft mouse | MRI and SERS imaging | Multifunctional AuNPs could not only preoperatively define orthotopic glioblastoma xenografts by MRI with high sensitivity and durability in vivo but also intraoperatively guide tumor excision with the assistance of a handheld Raman scanner | 114 |
| Hollow AuNPs | |||||
| Stabilizing ligand: PEG | Adenocarcinoma (A549 cells) | S.C. xenograft mouse | CT | The attenuation coefficient of hollow AuNPs is 5.3 times higher than that of the iodine-based contrast agent at the same concentration, demonstrating the potential of hollow AuNPs for CT imaging | 115 |
| Stabilizing ligand: PEG Targeting ligand: RGD Emitter: 64Cu |
Liver carcinoma vX2 tumor) | Orthotopic allograft rabbit | PET/CT | PET/CT images showed that the 64Cu-RGD- PEG-HAuNS showed higher tumor uptake than control groups at 24 h post injection | 116 |
| Stabilizing ligand: PEG Targeting ligand: RGD Emitter: 64Cu |
Glioblastoma (U87 cells) | Orthotopic xenograft mouse |
PET/CT PAI |
The dual-modality PAI and PET/CT imaging provided a promising targeted AuNP-mediated glioma therapy | 117 |
| Gold nanostars | |||||
| Stabilizing ligand: PEG Raman reporter: p-mercaptobenzoic acid |
Primary soft-tissue sarcomas | Transgenic mouse | CT Two-photon luminescence imaging |
The CT and optical results showed that 30 nm nanostars have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared with 60 nm counterparts | 118 |
| Stabilizing ligand: PEG | Breast cancer (4T1 cells) | S.C. allograft mouse | PAI | Novel Fe2O3@Au core/shell magnetic gold nanoflowers were synthesized through interactive growth of Au on Fe2O3 NPs. The nanoflowers exhibited remarkable SERS enhancement | 119 |
| Emitter: Gd3+ | Adenocarcinoma (A549 cells) | S.C. xenograft mouse | MRI, CT, and NIR fluorescence imaging | The existence of Gd3+ ions on GNCNs exhibits significant luminescence intensity enhancement for NIR fluorescence imaging, high X-ray attenuation for CT imaging, and reasonable r1 relaxivity for MRI | 120 |
| SERS labeling ligand: DTNB | Ovarian cancer (SKOv3) | S.C. xenograft mouse | Raman spectroscopy | The SERS Au nanostars were developed as a highly sensitive contrast agent for tumor detection in xenografted mice | 121 |
| Gold nanocages | |||||
| Stabilizing ligand: PEG Emitter: 64Cu |
Breast cancer (EMT-6 cells) | S.C. xenograft mouse | PET/CT | PET/CT images clearly showed rapid localization of the 64Cu -PEG-AU nanocages in tumor at 1 h post injection with the administration of a trace amount | 122 |
| Gold nanoprisms | |||||
| Stabilizing ligand: PEG | Colorectal cancer (HT-29 cells) | S.C. xenograft mouse | PAI | PEGylated Au nanoprisms showed the capacity to penetrate tumors and provided a high- resolution signal amplifier for optoacoustic imaging | 123 |
| Gold nanotripods | |||||
| Stabilizing ligand: PEG Targeting ligand: RGD |
Glioblastoma (U87 MG cells) | S.C. xenograft mouse | PAI | i.v. injection of RGD-conjugated Au-tripods showed PAI contrasts in tumors up to threefold higher than for the blocking group (coinjection with RGD) | 124 |
Abbreviations: AIE, aggregation-induced emission; AuNPs, gold NPs; BSA, bovine serum albumin; CET, cetuximab; CT, computed tomography; DAPTA, D-Ala1-peptide T-amide; DTNB, 5,5-dithio-bis-(2-nitrobenzoic acid); FA, folic acid; GC, glycol chitosan; GNRs, gold nanorods; HA, hyaluronic acid; ICG, indocyanine green; i.v., intravenous; LbL, layer-by-layer; MMP, matrix metalloproteinase; MPNA, magnetoplasmonic nanoassembly; MRI, magnetic resonance imaging; NGAL, neutrophil gelatinase-associated lipocalin; NIR, near-infrared; NPs, nanoparticles; PAI, photoacoustic imaging; PB, Prussian blue; PEG, polyethylene glycol; PEI, polyethylenimine; PET, positron emission tomography; PLGA, poly(lactic-co-glycolic acid); PPAA, plasma-polymerized allylamine shell; PTT, photothermal therapy; SPECT, single-photon emission CT; S.C., subcutaneous; SERS, surface-enhanced Raman spectroscopy; TAT, transactivator of transcription; TNBC, triple-negative breast cancer.