Table 1 List of various functionalizing agents used for AuNPs-based multimodal cancer therapy
Functionalizing agent | Composition | Cancer type | Size and Zeta potential | Type of therapy | Cell line/animal model | Result | References |
|---|---|---|---|---|---|---|---|
EGF/HER-2/CD133 antibody | PLGA coated AuNSs | Breast | 248.3 nm, − 14.7 mV | PTT imaging (808 nm laser (1 W/cm2) for 10 min)/USMR | SKBR3 cells and MDA-MB-231 cell line | Dual-modal molecular probe to provide US/MR contrast-enhanced imaging in vitro, as well as the targeted PTT effect of breast cancer cells induced by NIR-absorbed Au nanoshells | [109] |
Au nanocage | Breast | 61.2 ± 4.85 nm, − 8.2 ± 1.25 mV | PTT (808 nm laser at 1 W/cm2, 5 min) | 4T1cell/Female BALB/c mice | Significant improvement in the therapeutic effect of PTT by improved targeting efficiency and enhanced accumulation and uptake of nanoparticles in the cancer cells | [200] | |
AuNPs functionalized with Ce6 | Breast | 21 nm | PDT (660 nm, 25 mW/cm2) | MDA-MB-468 and MCF 10A | PDT with Bifunctional EGF-Ce6 functionalized AuNPs efficiently induced cell death in TNBC cells by increasing ROS levels, while it did not affect normal cells | [51] | |
AuNS@ICG-Ab | Breast | 135.3 nm, − 31.5 mV | PTT(808 nm, 0.5 W/cm2, 3 min)/PDT (633 nm, 0.8 W/cm2, 5 min)/immunotherapy | CIK cells, SK-BR-3/ C57BL/6 and BALB/c nude mice | The AuNS@ICG-Ab-CIK can effectively diagnose and treat cancer | [39] | |
AuNRs | Breast | 55.1 ± 1.7 Length and 14.1 ± 1.1 nm diameter, 43.2 mV | Fluorescence imaging-guided (PDT 635 nm, 0.5 W/cm2, 2 min (/PTT 808 nm, 2.0 W/cm2, 5 min | MCF-7 cells /female BALB/c nude mice | MCF-7 cells could efficiently generate reactive oxygen species (ROS) and heat, and be more efficiently killed by a combination of PDT and PTT as compared with individual therapy | [186] | |
anti-EGFR antibodies AuNRs | Lung | 40 nm width and 148 nm length | PPT (854 nm, 1.5 W)/PA imaging | A549 cells | Anti-EGFR tagged AuNRs much larger accumulation as compared to untagged one. It was shown that the combination of pulse wave laser illumination of targeted nanoparticles produced a reduction of 93% ± 13% in the cell viability compared with control exposures, which demonstrates a possible application for minimally invasive therapies for lung cancer | [201] | |
Nanobioconjugate AuNPs | Lung | 63.91, − 14.7 | PDT (673.2 nm, 10 J/cm2) | A549, CD133 + , CD44 + and CD56 + cells | AlPcS4Cl-AuNP-Ab nanobioconjugate (NBC) are biocompatible and NBC photodynamic effect induces the preferred cell death, but it also shows enhanced and effective lung CSC destruction | [53] | |
Au nanostars | Prostate | 120 nm, − 22.47 mV | PTT((808 nm, 0.8 W/cm2, 5 min/PDT (NIR-light irradiation, 7 min)/CTX | PC3 cell-line/ male BALB/c athymic nude mice | Au nanostars@IR820/DTX-CD133 for in vitro and in vivo therapy achieves the excellent antitumor effects of the synergistic PTT/PDT/CT strategies under the NIR-light irradiation | [155] | |
Serum albumin (SA) | BSA-AuNCs | Breast | – | PDT (λ = 405 nm, 66 mW/cm2) | MCF-7 and MDA-MB-23 | BSA-AuNCs can induce efficient cytotoxicity | [202] |
PLGA surface modified AuNRs | Colon | 245.8 nm, − 8.6 mV | PTT (808 nm, 1.5) for 4 min) /CTX | CT26, and MCF7 | The HADP NPs showed promising combined PTT- and chemotherapeutic effects without inducing undesired side effects on a murine colon cancer animal model | [203] | |
BSA modified AuNR | Lung | 50 nm, + 35 mV | PTT(808,1 W/cm2 for 8 min) | Lewis cells/female C57BL/6 mice | Excellent biosafety of AuNRBR/N without laser irradiation, and exhibited superior therapeutic effect on Lewis tumor due to the optimal tumor targeting of neutrophils and multistage delivery of AuNRBR for deep tumor diffusion, which also improved the survival rate of mice | [92] | |
AuNPs | Liver | 49 nm | PTT (2 W, 808 nm, 30 min) | HepG2 and HepB5 cells | Alb-AuNPs showed no cytotoxic effect, Alb-functionalized AuNPs leads to increased intracellular uptake in liver cancer cells by selective targeting of Gp60 receptors | [112] | |
Glutathione | Hyaluronic acid functionalized AuNRs | Breast | Length 55.1 ± 1.7 and diameter 14.1 ± 1.1 nm, 43.2 mV | Fluorescence imaging-guided (PDT 635 nm, 0.5 W/cm2, 2 min (/PTT 808 nm, 2.0 W/cm2, 5 min | MCF-7 cells /female BALB/c nude mice | MCF-7 cells could efficiently generate reactive oxygen species (ROS) and heat, and be more efficiently killed by a combination of PDT and PTT as compared with individual therapy | [186] |
Glutathione corona coated AuNPs | Liver | Aggregated AuNP, 239 ± 73 nm and 254 ± 64 nm, − 33 mV | PTT (760 nm, 1.26 s) | Hep G2 line | a-DG-AuNPs readily internalized in HeP G2 cells, efficient cancer cell ablation occurs via two-photons excitation PTT | [122] | |
Lactoferrin (LF) | AuNRs | Liver | 70 nm in length and 11.5 nm in width, − 15 mV | PTT (980 nm, 0.5 W/cm2) | HepG2 cells/nude mice | Surface coated and medium size AuNRs shown enhanced uptake and retention by cancer cell, AuNR70@PEG-LF shown completely destroyed the tumors without recurrence after one single treatment achieved due to synergistically via proper size and ligand conjugation | [124] |
Lactoferrin-conjugated AuNP | Brain | 5 nm | PTT (532 nm NIR diode laser (4 W/cm2) for 5 min | Human GBM U87MG cell line/Male BALB/c nude mice | Orally administered Lf-PEG-AuNP exhibit an outstanding temperature rise in GBM and significantly reduce tumor volume under laser irradiation | [129] | |
Folic acid (FA) | Si coated AuNPs | Breast | 25 nm, − 19.7 mV | PTT (810 nm, 185 mW, 139 s) | MCF-7 and MDA-MB-231 cells | MTX-FA loaded Au@SiO2NPs had shown improved the efficacy of laser therapy in breast cancer cell destruction | [47] |
AuNPs | Brain | 10 ± 2 nm | PTT (808 nm, 0.8 W/cm2) | C6 glioma | Photoresponsive Au-decorated polymer nanoparticles (FA-PGPNPs) are promising nanoprobes with targeting ability, enhanced tumor PDT, cell tracking, and PTT effect | [131] | |
Peptides | Mesoporous silica-coated gold cube | Breast | 116.5 nm, 24.5 ± 1.6 mV to 5.6 ± 0.5 mV | PDT ( 635 nm)/PTT (808 nm)/multimodal bioimaging | 4T1 and L929 cell line/ nude mice | Showed high therapeutic performance and multiplexed imaging, which provides an innovative paradigm for targeted tumor therapy | [204] |
AuNPs | Colon | 56.1 ± 0.3 and 62.8 ± 0.4 nm, − 30.1 ± 1.7 and − 20.8 ± 1.3 mV | PTT (808 nm laser (2 W/cm2) for 5 min)/PA | HUVEC and HCT-116 cell line/female nude mice | The Au-RRVR nanoparticles could form large aggregates within tumorous tissue resulting in improved tumor accumulation and retention, which can further activate the PA and PTT effect of AuNPs for sensitive imaging and efficient therapy of tumors | [205] | |
Mesoporous silica coted AuNPs | Lung | 20 nm | PTT (808 nm laser, 1.2, 0.9, 0.6, and 0.3 W/cm2 for 5 min)/CTX | A549, HOB, and HBMSC cells/mice | Au@MOF@MS-ICG-dYNH-PAA (AMMD) shows enhanced cellular uptake on tumor cells. Benefiting from this ultra-high affinity to tumor cells and the photothermal effect of ICG, the dual-drug-loaded AMMD (BCAMMD) modified with ICG exhibits superior therapeutic efficacy on spinal tumors | [206] | |
Polypeptide-modified AuNCs | Lung | 85.2 nm, − 17.44 ± 2.48 | PDT (633 nm, 100 mW/cm2 for 5 min)/CTX/fluorescence imaging | A549 cells, Female BALB/c-nude mice | Nanoprobes could be efficiently internalized into A549 cells and then significantly enhance the mortality of cancer cells compared with free Ce6 and DOX, and shown excellent tumor targeting ability, long blood circulation time, and could remarkably inhibit the growth of tumor | [29] | |
(PD-L1) peptides modified gold nanoprisms | Lung | 3.41 ± 5.22 mV | PTT (633 nm, 0.8 W/cm, 1 min to 10 min)/PDT(633 nm (0.8 W/cm2, 10 min)/PA imaging | HCC827 and A549 cells/female BALB/c nude mice | AuNPs@PEG/Ce6-P are biocompatible and significantly suppress tumor growth through PTT and PDT from AuNPs and Ce6, respectively | [138] | |
AuNPs | Liver | 72.4 nm, − 12.5 ± 2.1 mV | PTT (0.8 W/cm2, 10 min, 1 min/PDT (808 nm, 6 min) | HCC-LM3 cells/nude mice | Excellent biocompatibility, high absorption by cancer cells, enhanced PDT/ PTT combination therapy under laser irradiation, significant inhibition of tumor growth | [56] | |
Au nanostars | Lung | 80 nm, − 10.1 mV | PTT/PDT/PA | A549 cancer/ Female BALB/C nude mice | Au nanostars@BSA/I-MMP2 exhibited excellent stability and biocompatibility and effectively internalized by A549 cancer cells and exhibited remarkable antitumor efficacy | [116] | |
AuCNs | Pancreatic | 53 nm, − 17 and − 10 mV | PTT (750 nm, 2 W/cm2,5 min)/PDT (652 nm laser (50 m W/cm2, 5 min) | PANC1-CTSE/mice | The AuS-U11 represents a very promising imaging-guided PDT/PTT therapeutic agent for pancreatic tumor therapy, along with highly synergistic therapeutic effects against pancreatic tumors as well as the reduced side effects in normal pancreas tissue | [55] | |
AuNPs | Prostate | 13 nm after adding Serum alkaline phosphatase (ALP) AuNPs aggregated to 500 nm | PTT (650 nm, 5/cm2, 10 min | PC-3 cells, MCF-7/ male BALB/c nude mice | The AuNPs@Peptide can be enzymatically assembled into large aggregates and enhance the temperature of the tumor during PTT | [207] | |
Au nanostars | Prostate | 82.5 ± 6.5 nm in diameter with sharp edges, − 3.74 ± 0.09 mV | PTT (808 nm laser (optical density 2.5 W/cm2, 3 min) | PC-3, DU145, LNCaP, 3T3 cells/ nude mice | These nanostars have excellent light-thermal conversion efficiency in the NIR region, biocompatible surface and strong cellular penetration. MSCs loaded with the TAT-conjugated Au nanostars (TAT-Au nanostars) could facilitate the assembly of the nanostars in the lysosomes inside MSCs as an “engineering factory” and excrete the microvesicles loaded with Au nanostars for tumor recognition and distribution | [85] | |
AuNRs | Prostate | 52.33 ± 8.05 nm length, 13.99 ± 1.09 nm width, − 21.6 mV | PTT (808 nm, 0 to 5 W,/PDT (laser irradiated 2.5 and 5 W/cm2 | PC-3 cells,/ Balb/C nude mice | In vitro study with the castration resistance prostate cancer cell exhibited a significant PTT effect as well as enhanced thermodynamic therapy via generating free radicals. P-p38 and p-JNK proteins, as key proteins involved in the cells’ stress responses, were found to be upregulated by the synergetic treatment | [148] | |
Aptamers | Deoxyribonucleic acids-gold particle | Breast | 13 nm | PTT/PDT (660 nm, 0.8 W/cm2 for 5 min)/in situ imaging-guided/CTX, gene therapy | MCF-7 cells, HeLa cells, L02 cells/ female nude mice | The Apt-DNA-Au nanomachine provides superior in vitro and in vivo sensitivity and specificity of the Apt-DNA-Au nanomachine for TK1 mRNA have achieved real-time monitoring of the dynamic change in tumors during therapy | [179] |
AuNPs modified with AS1411 and DNA | Colon | 24.42 nm, − 35.8 mV | PTT(808 nm, 1 or 2 W/cm2 for 5,10,30, 60,120 min)/CTX | SW480 cells | The AS1411 NPs exhibited the most efficient cytotoxicity and markedly enhanced inhibition effect on cells proliferation to SW480 cells under laser exposure when compared to the NPs merely with PTT or chemotherapy | [117] | |
AS1411 aptamer modified Au nanocage | Lung | 10 nm | PTT (808 nm 1 W/cm2 for 5 min), /CTX/genetic | NCI-H889/ BALB/c nude mice | The combined genetic, chemotherapeutic, and PTT treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group | [177] | |
Aptamer-modified HAu nanoshells | Lung | 10–20 nm to 100–200 nm | PTT (808 nm, for 5 min) | MRC-5, MCF-10A, A549, MCF-7 | Aptamer-modified nanoparticles were accumulated selectively in tumor cells (A549, MCF-7) and this fact contributed to the reduction of tumor spheroids viability and size | [208] |