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]