Table 2.
A summary of studies on the in vivo use of gold nanocomplexes in systemic cancer PTT and PDT
| AuNP type | Functional ligand | Cancer type | In vivo model | Laser | Comment | Reference |
|---|---|---|---|---|---|---|
| PTT | ||||||
| Au nanorods | Stabilizing ligand: PEG | Melanoma (MDA- MB-435 cells) | S.C. xenograft mouse | 810 nm laser 2 w/cm2 5 min |
A single i.v. injection of PEG-Au nanorods enabled destruction of the irradiated human xenograft tumors in mice | 143 |
| Au nanorods | Stabilizing ligand: PEG Targeting ligand: RGD |
Glioblastoma (U87 MG cells) | S.C. xenograft mouse | 808 nm laser 1 w/cm2 10 min |
Au nanorods showed high tumor-targeting ability via receptor-mediated pathway and were successfully used for PTT | 144 |
| Au nanorods | Coating material: silica | Breast cancer (4T1 cells) | S.C. allograft mouse | 808 nm laser 4 w/cm2 10 min |
When Au nanorods were stimulated with the NIR laser, DOX was released for synergistic therapeutic effect in combination with PTT | 145 |
| Au nanorods | Stabilizing ligand: PEG and dendrimers | Colon carcinoma (26 cells) | S.C. allograft mouse | 808 nm laser 0.24 w/cm2 10 min |
The combined photothermal-chemo treatment using AuNPs containing DOX for synergistic PPT and chemotherapy exhibited higher therapeutic efficacy than either single treatment alone | 146 |
| Au nanorods | Coating materials: PvP and AgNO3 Targeting ligand: aptamer |
Adenocarcinoma (A549 cells) | S.C. xenograft mouse | 980 nm laser 0.84 w/cm2 5 min |
The resultant AuNPs specifically accumulated into tumor tissues and induced PTT for dramatically stronger antitumor effect upon NIR laser irradiation | 147 |
| Au nanorods | Au nanorods encapsulated in CHI/sodium ALG microcapsules | Breast cancer (4T1 cells) | S.C. allograft mouse | 808 nm laser 3.83 J/cm2 5 min |
Self-assembled Au nanorods in bilayer- modified microcapsules localized at tumor sites, generated vapor bubbles under NIR exposure, and subsequently damaged tumor tissues | 148 |
| Au nanorods | Stabilizing ligand: PEG Targeting ligand: antibody for anaerobic bacteria (C difficile) |
Adenocarcinoma (A549 cells) | S.C. xenograft mouse | 808 nm laser 0.5 w/cm2 10 min |
The C. difficile spores was i.v. injected for 2 days, followed by the injection of antibody-Au nanorods to specifically target the germination of the C. difficile spores in tumor tissues (low level of oxygen microenvironment). Under the NIR laser, antibody-Au nanorods completely inhibited tumor growth | 149 |
| Au nanorods | Stabilizing ligand: dendrimer | Non-small-cell lung cancer (PC-9 cells) | S.C. xenograft mouse | 808 nm laser 3.6 w/cm2 8 min |
Dendrimer-stabilized Au nanorods (DSAuNRs, sub-10 nm in length) showed significantly enhanced absorption in the NIR region compared with dendrimer- stabilized Au nanospheres. The tumor growth was significantly retarded by the photothermal efficiency of DSAuNRs | 150 |
| Au nanorods | Coating material: silica Targeting ligand: antibody for CXCR4 |
Gastric cancer (MGC803 cells) | S.C. xenograft mouse | 808 nm laser 1.5 w/cm2 3 min |
iPS cells were transfected with the resulted AuNRs@SiO2@CXCR4 via receptor-mediated pathway. The transfected iPS cells were homing to tumor tissues, and the tumor growth was significantly slowed down by the photothermal efficiency of AuNRs@ SiO2@CXCR4 | 151 |
| Au nanoshells | Multilayered AuNPs with silica and gold, also termed Au nanomatryoshkas | Breast cancer (MDA-MB-231 cells) | Orthotopic xenograft mouse | 810 nm laser 2 w/cm2 5 min |
Au nanomatryoshkas exhibited improved PTT efficacy when compared with conventional gold nanoshells | 152 |
| Au nanoshells | Stabilizing ligand: PEG | Breast cancer (4T1 cells) | S.C. allograft mouse | 808 nm laser 1 w/cm2 10 min |
In combination with chemotherapeutics, the resultant Au nanoshells achieved complete destruction of the tumors at a low laser irradiation without weight loss or recurrence of tumors | 153 |
| Au nanoshells | Stabilizing ligand: PEG Inner core: PLGA NPs |
Glioblastoma (U87 MG cells) | S.C. xenograft mouse | 808 nm laser 1.5 w/cm2 1.5 min |
The temperature of tumor treated with the resultant Au nanoshells was rapidly increased to 46.6 °C, which released DOX for synergistic therapeutic effect in combination with PTT | 154 |
| Au nanoshells | Stabilizing ligand: PEG Inner core: PEI-PASP (DIP/MEA) NPs |
Liver cancer Bel-7402 cells | S.C. xenograft mouse | 808 nm laser 1.5 w/cm2 2 min |
A polymeric vesicle encapsulating DOX was prepared and then decorated with a gold layer using a modified method of in situ gold seed growth. The NIR light energy was converted into heat, which killed cancer cells in the vicinity and induced the rupture of nanoshell to release DOX inside tumor | 155 |
| Au nanoshells | Stabilizing coating: MPCMs Inner core: silica |
Breast cancer (4T1 cells) | S.C. allograft mouse | 808 nm laser 1 w/cm2 5 min |
MPCM-coated Au nanoshells presented longer blood circulation and tumor accumulation in a xenograft mouse model of breast cancer. Tumor growth was significantly slowed down by irradiation of NIR laser | 156 |
| Au nanostars | Stabilizing ligand: PEG Targeting ligand: RGD |
Glioblastoma (U87 MG cells) | S.C. xenograft mouse | 790 nm laser 1 w/cm2 10 min |
RGD-Au nanostars were designed to specifically target overexpressed integrin αvβ3 on tumor neovasculature, enabling highly sensitive PTT | 157 |
| Au nanostars | Surface coating: organosilica | Breast cancer (MDA-MB-231 cells) | S.C. xenograft mouse | 808 nm laser 0.5 w/cm2 5 min |
In 5 min of irradiation, the temperature at the tumor region of mice treated with Au nanostars increased remarkably to about 57°C | 158 |
| Au nanocages | Targeting ligand: HA | Breast cancer (MDA-MB-231 cells) | S.C. xenograft mouse | 808 nm laser 1 w/cm2 5 min |
HA-coated Au nanocages accumulated inside tumor tissues via HA-CD44 interaction. Under the NIR stimulation, HA-coated Au nanocages significantly slowed down the tumor growth. In addition, a complete tumor inhibition was achieved when combined with chemotherapy | 159 |
| Au nanocages | Gold surface was coated with PvP and RBC membranes | Breast cancer (4T1 cells) | S.C. allograft mouse | 850 nm laser 1 w/cm2 10 min |
RBC-AuNCs exhibited significantly enhanced in vivo blood retention and circulation lifetime. with NIR laser, RBC-AuNCs achieved 100% survival of tumor-bearing mice over a span of 45 days | 160 |
| Hollow Au nanospheres | Stabilizing ligand: PEG Targeting ligand: a peptide (TNYL) |
Ovarian carcinoma (SKOv3 cells) | S.C. xenograft mouse | 808 nm laser 1.5 w/cm2 3 min |
Under NIR laser irradiation, the resultant hollow Au nanospheres induced PTT for dramatically stronger antitumor effect against EphB4-positive tumors than EphB4- negative tumors | 161 |
| Hollow Au nanospheres | Stabilizing ligand: PvP and citrate | Ovarian carcinoma (SKOv3 cells) | S.C. xenograft mouse | 808 nm 3.0 w/cm2 10 min |
The resultant AuNPs exhibited a significantly enhanced surface plasmon absorption in the NIR region, inducing an efficient photothermal conversion and stronger anticancer ability under NIR laser irradiation | 162 |
| Au nanoclusters | A pH-sensitive ligand inducing Au nanoclusters in mild acidic environments | Fibrosarcoma (HT-1080 cells) | S.C. xenograft mouse | 660 nm laser 0.5 w/cm2 1 min |
MSCs were first transfected with the resultant AuNPs. The MSC-AuNPs showed a 37-fold higher tumor-targeting efficiency and resulted in a significantly enhanced anticancer effect upon irradiation | 163 |
| Au nanoplates | Stabilizing ligand: PEG | Breast cancer (4T1 cells) | S.C. allograft mouse | 808 nm laser 0.5 w/cm2 10 min |
PEGylated AuNPs presented good biocompatibility, prolonged blood circulation, and relatively high tumor accumulation. The NIR laser irradiation induced PTT and retarded tumor growth | 164 |
| PDT | ||||||
| Au nanospheres | Coating materials: heparin Photosensitizer: PhA |
Adenocarcinoma (A549 cells) | S.C. xenograft mouse | 670 nm laser 3 mw/cm2 30 min |
The PDT effects of PhA-H/AuNP significantly retarded tumor growth in comparison with PhA alone | 165 |
| Au nanorods | Coating materials: silica and PEG Photosensitizer: PPIX | Adenocarcinoma (HeLa cells) | S.C. xenograft mouse | 532 nm laser 25 mw/cm2 15 min |
A real-time and specific in vivo SERS and fluorescence detection method using the resultant AuNPs was applied for tumor detection and subsequent PDT | 166 |
| Au nanorods | AuNPs encapsulated in Pluronic nanogel Photosensitizer: Ce6 | Squamous carcinoma (SCC7 cells) | S.C. allograft mouse | 655 nm laser 20 J/cm2 30 min |
A remarkable synergy for anticancer treatment was observed when PDT was applied before PTT, both in vitro and in vivo | 167 |
| Au nanorods | Stabilizing ligand: PEG Targeting ligand: FA |
Melanoma (B16F0 cells) | S.C. allograft mouse | 915 nm 130 mw/cm2 15 min |
GNRs alone can sensitize the formation of singlet oxygen and exert dramatic PDT effects on complete destruction of tumors in mice under light excitation | 168 |
| Au nanorods | Stabilizing ligand: CHI Photosensitizer: ICG |
Liver cancer (H22 cells) | S.C. allograft mouse | 808 nm laser 2 w/cm2 10 min |
The resultant NPs have been successfully prepared to facilitate in vivo PDT resulting in abundant ROS produced by ICG under NIR irradiation | 142 |
| Au nanorods | Stabilizing ligand: poly(allylamine hydrochloride) Photosensitizer: RB |
Oral squamous carcinoma | A carcinogen was topically injected into the left cheek pouch mucosa | 532 nm green light 1.79 w/cm2 10 min |
The PDT-only treatment achieved a 46.5% tumor inhibition rate; when combined with PTT effects under NIR laser stimulation, 95.5% tumor inhibition rate was achieved | 169 |
| Au nanorods | Endosome disruptive ligand: Tat/HA2 Photosensitizer: AlPcS4 |
Adenocarcinoma (HeLa cells) | S.C. xenograft mouse | 808 nm laser 400 mw/cm2 15 min and 680 nm LED light 10 mw/cm2 40 min |
AuNRs absorbed an SPR wavelength (808 nm) and converted it into heat, causing the release of AlPcS4. Subsequently, upon illumination at 680 nm, the released AlPcS4 transferred the photon energy to oxygen molecules, stimulating ROS generation to slow down the tumor growth | 170 |
| Au nanocages | Stabilizing ligand: PEG Photosensitizer: HPPH |
Colon cancer (Colon-26 cells) | S.C. allograft mouse | 665 nm laser 75 mw/cm2 30 min |
The tumor growth was suppressed due to the enhanced phototoxicity of the HPPH- Au nanocages under the laser stimulation | 171 |
| Au nanoclusters | AuNPs encapsulated in silica Photosensitizer: Ce6 |
Melanoma (MDA- MB-435 cells) | S.C. xenograft mouse | 671 nm laser 100 mw/cm2 10 min |
The resultant AuNCs@SiO2-Ce6 completely inhibited tumor growth in mice due to PDT effects when compared with Ce6 alone and AuNCs@SiO2 alone | 172 |
| Au quantum clusters | Stabilizing ligand: lipoic acid Targeting ligand: FA Photosensitizer: PPIX |
Glioma (C6 cells) | S.C. xenograft mouse | 532 nm laser 1.5 w/cm2 15 min |
Under the laser stimulation, singlet oxygen efficiency of the resultant NPs was significantly higher when compared with that of the PPIX alone | 173 |
Abbreviations: ALG, alginate; AuNPs, gold NPs; C. difficile, Clostridium difficile; Ce6, chlorin e6; CHI, chitosan; DOX, doxorubicin; FA, folic acid; GNRs, gold nanorods; HA, hyaluronic acid; HPPH, 3-devinyl-3-(1′-hexyloxyethyl)pyropheophorbide; ICG, indocyanine green; iPS, Induced pluripotent stem; i.v., intravenous; LED, light-emitting diode; MPCMs, macrophage cell membranes; MSCs, mesenchymal stem cells; NIR, near-infrared; NPs, nanoparticles; PDT, photodynamic therapy; PEG, polyethylene glycol; PEI, polyethylenimine; PEI-PAsp (DIP/MEA), polyethylenimine-b-poly(2-diisopropylamino/2-mercaptoethylamine) ethyl aspartate; PhA, pheophorbide a; PLGA, poly(lactic-co-glycolic acid); PPIX, protoporphyrin IX; PTT, photothermal therapy; PVP, polyvinylpyrrolidone; RB, Rose Bengal; RBC, red blood cell; ROS, reactive oxygen species; S.C., subcutaneous; SERS, surface-enhanced Raman spectroscopy; SPR, surface plasmon resonance.