A review of small molecules and drug delivery applications using gold and iron nanoparticles

Figures & data

Table 1 Overview of Au-NPs/5-FU and their applications

Nanoparticles	Drugs	Applications	References
Au-NPs/thioglycolic acid and glutathione	5-FU	Patients having colorectal cancer	^Citation21
Au-NPs/PEG	5-FU	M139 and M213 cells	^Citation27
Porphyran-capped Au-NP-modified carbon paste electrode	5-FU	Electrochemical sensor	^Citation30
Au-NPs/polyamic acid	5-FU	HeLa cells	^Citation31
Fluorescent chitosan/silver–gold nanocomposite	5-FU	Colorimetric sensing and 5-FU delivery	^Citation32
Au-NPs/chitosan	5-FU	HepG2	^Citation33
Au-NPs capped with cetyltrimethylammonium	5-FU	HaCaT	^Citation34

Abbreviations: Au-NPs, gold nanoparticles; 5-FU, 5-fluorouracil; PEG, polyethylene glycol.

Figure 1 Targeted delivery of 5-FU to cholangiocarcinoma cells using folic acid. Note: Data from Ngernyuang et al.²⁷

Abbreviation: 5-FU, 5-fluorouracil.

Table 2 Overview of Au-NPs/FA and their applications

NPs	Drugs/targeting agent	Applications	References
Glutathione-capped Au-NPs	FA	HeLa and mouse fibroblast (FB) cells	^Citation35
Polyethylenimine-entrapped Au-NPs	FA	KB-HFAR cells and KB-LFAR cells	^Citation37
Negatively charged Au-NPs with the transferrin targeting ligands and positively charged Au-NPs with the folate receptor targeting ligands	FA	Prostate cancer cells	^Citation41
Au-NPs prepared by using a strong antioxidant quercetin and dextran sulfate as a stabilizing agent	FA	NIH 3T3 FB and human breast cancer cell lines (MCF-7)	^Citation42
Au-NPs functionalized with FA	FA	Cervix cancer cells	^Citation43
Positively charged Au-NPs capped with folate quaternary chitosan	FA	Human umbilical vein endothelial cells	^Citation44
Gum kondagogu-capped Au-NPs	FA	A549 (lung cancer) cells	^Citation38
Folate-conjugated Au-NPs	FA	KB cancer cells and L929 normal cells	^Citation45
Folate-conjugated gold-photoactive polymer NPs	FA	C6 glioma brain cancer cells	^Citation46
Au-NPs on FA-modified dendritic mesoporous silica-coated reduced graphene oxide nanosheets	FA	MCF-7 (human breast carcinoma cell lines) and A549 (human lung carcinoma cell lines)	^Citation39
Au-NPs/dimethyldioctadecylammonium/bromide/dioleoylphosphatidylethanolamine	FA	MCF-7 and A549	^Citation47
Modified Au-NPs with covalently bonded thiol linkers	FA	MDA-MB-231	^Citation48
Gold nanorods/amphiphilic polysaccharide-based graft copolymer and an amino derivative of the α,β-poly(N-2-hydroxyethyl)-d, l-aspartamide	FA	16HBE and HDFa	^Citation49
Gold nanobipyramids	FA	MCF-7	^Citation40
Biocapped Au-NPs using hirsutus leaf extract	FA	HeLa, RKO, and A549	^Citation50
FA-Au@poly(acrylic acid)/mesoporous calcium phosphate Janus NPs	FA	HeLa	^Citation51
Au-NPs modified with thionine	FA	A549	^Citation52
Poly(ethylene glycol)-coated gold@iron oxide core–shell NPs	FA	KB and MCF-7	^Citation53

Abbreviations: Au-NPs, gold nanoparticles; FA, folic acid; HBE, human bronchial epithelial cells; HDFa, human dermal fibroblasts; MDA-MB, typical human breast cancer cells; RKO, human colon carcinoma cell line; HeLa, cell line derived from cervical cancer cells; HFAR, high folate receptor; LFAR, low folate receptor; HFAR, high folic acid receptor; LFAR, low folic acid receptor; NPs, nanoparticles.

Figure 2 Bioconjugation of gold nanobipyramids for the detection of SERS and targeted photothermal therapy in breast cancer.

Note: Data from Feng et al.⁴⁰

Abbreviations: SERS, surface-enhanced raman scattering; PTT, photothermal therapy; EM, electromagnetic field.

Table 3 Overview of Au-NPs/DOX, Au-NPs/paclitaxel (PTX), and their applications

NPs	Drugs/targeting agent	Applications	References
Au-NPs pectin (Pec-Au-NPs)	DOX	Breast cancer cells	^Citation57
DOX-loaded fucoidan-capped Au-NPs	DOX	Human breast cancer cells	^Citation54
Protein-gold cluster-capped mesoporous silica NPs	DOX/gemcitabine	A549 lung cancer cells	^Citation58
Gelatin-DOX conjugate (GLT-DOX)-coated Au-NPs (DOX-GLT/EGCG Au-NPs)	DOX	PC-3 cancer cell	^Citation59
Biosynthesized Au-NP Peltophorum pterocarpum	DOX	Cancer cells (A549, B16F10) and tumor growth in an in vivo model	^Citation60
Gelatin-coated Au-NPs	DOX	MCF-7 breast cancer cells	^Citation61
Au-NPs/polyvinylpyrrolidone	DOX	A549, H460, and H520 lung cancer cells	^Citation55
DOX-loaded Au-NPs	DOX	A2780 human ovarian cancer cell line	^Citation56
Pectin-capped Au-NPs	DOX	Human Caucasian hepatocyte cells	^Citation62
Human serum albumin (HSA)-coated gold nanorods (GNR/PSS/HSA NPs)	DOX	Combined cancer photothermal therapy and chemotherapy	^Citation63
Gold nanoplatform targeting carbonic anhydrase IX epitope	DOX	HT29 tumor cells	^Citation64
Oligonucleotide-conjugated Au-NP	DOX	SW480 cells	^Citation65
Oligonucleotides attached to Au-NP	DOX	SW480	^Citation65
Colloidal Au-NPs	DOX	HepG2	^Citation66
Au/Fe3O4	DOX	Targeted chemo-photothermal	^Citation67
Cisplatin and DOX-bioconjugated bromelain-encapsulated Au-NPs	DOX	MG-63 and Saos-2	^Citation68
Platinum (core)-gold (shell) bimetallic NPs with chitosan	DOX	HEK293, Caco-2, HepG2, and MCF-7	^Citation69
Magnetic and Au-NP-embedded silica nanoshuttles	DOX	HeLa	^Citation70
Ultrasmall Au-NPs were appended to the openings of mesoporous silica NPs	DOX	A549	^Citation71
Multifunctional Au-NP	DOX	A549	^Citation72
Fetuin-conjugated Au-NPs	DOX	NCI-H460	^Citation73
Au-NPs coated	DOX	VX2 and raw 264.7	^Citation74
Asialoglycoprotein receptor/PTX-conjugated Au-NPs	PTX	Liver tumor (HepG2) cells	^Citation75
Gold NP-coated pluronic-b-poly(l-lysine) NPs	PTX	MDA-MB-231 cells	^Citation76
Au-NPs with two-layer (hexadecanethiol/phosphatidylcholine) and three-layer (with high-density lipoprotein) NPs	PTX	Lung cancer	^Citation77
Biocompatible Au-NPs/chitosan oligosaccharide	PTX	MDA-MB-231	^Citation78
Gold-PTX nanoconjugate	PTX	H460 and H460PTX	^Citation79
Dithiocarbamate-functionalized PAMAM dendrimer used to cross-link the shell of arginine Au-NPs	PTX	B16F10 cells	^Citation80
Polymer-coated gold/graphene hybrid	PTX	MCF-7 and 16 HBE	^Citation81
Liposomes and Au-NPs used to construct a liposome with a hybrid cluster bomb structure	PTX	HepG2	^Citation82
Multifunctional nanoparticulate theranostic system simultaneously encapsulating PTX, Au-NPs, and iron oxide NPs in poly(ethylene oxide)-block-poly(ε-caprolactone)	PTX	MCF-7 and MDA-MB-231	^Citation83

Abbreviations: Au-NPs, gold nanoparticles; DOX, doxorubicin; NPs, nanoparticles; PAMAM, poly(amidoamine); PTX, paclitaxel; HSA, human serum albumin; PSS, poly(sodium 4-styrenesulfonate).

Figure 3 Protein-gold cluster-capped mesoporous silica NPs for high drug loading, autonomous gemcitabine/DOX codelivery, and in vivo tumor imaging.

Note: Data from Croissant et al.⁵⁸

Abbreviations: Au-NCs, gold nanoclusters; DOX, doxorubicin; MSN, mesoporous silica nanoparticle; NPs, nanoparticles.

Figure 4 PTX-loaded chitosan oligosaccharide-stabilized Au-NPs as novel agents for drug delivery and photoacoustic imaging of cancer cells.

Note: Data from Manivasagan et al.⁷⁸

Abbreviations: Au-NPs, gold nanoparticles; COS, chitosan oligosaccharide; PTX, paclitaxel.

Figure 5 Overall scheme for the biosynthesis of Au-NPs using COS, subsequent loading of PTX on COS-stabilized Au-NPs (COS Au-NPs), and the possible mechanism for the cellular uptake of loaded COS-stabilized Au-NPs (PTX-COS Au-NPs) in MDA-MB-231 cancer cells.

Note: Data from Manivasagan et al.⁷⁸

Abbreviations: Au-NPs, gold nanoparticles; COS, chitosan oligosaccharide; PTX, paclitaxel.

Table 4 Overview of iron oxide nanoparticles/drugs and their applications

Nanoparticles	Drugs/targeting agent	Applications	References
Magnetic mesoporous silica gated with doped carbon dot	5-FU	Fluorescence imaging of Sla-overexpressed HePG2 cancer cells	^Citation103
Magnetic iron oxide/mesoporous silica nanocomposites (m-MCM-41)	5-FU	Drug release system	^Citation104
Chitosan-co-PEG/poly(glycerol sebacate)-co-PEG-coated iron oxide	5-FU	Carrier for 5-FU anticancer, HT29 cell line	^Citation105
Polylactic-co-glycolic acid (PLGA) NPs as 5-FU carriers with/without iron oxide core	5-FU	Carrier for 5-FU anticancer human colon cancer cell line HT29	^Citation106
PLGA-coated magnetite nanographene oxide	5-FU	Rabbit plasma	^Citation107
Polycaprolactone (PCL)/chitosan (CHI)-coated superparamagnetic iron oxide nanographene oxide (SPION-NGO)	5-FU	CT26 colon cancer cell line	^Citation108
Magnetic NPs Fe3O4	5-FU	7,901 cancer cells	^Citation119
Magnetic field-sensitive methylcellulose and PCL gels	5-FU	Targeted and controlled release	^Citation110
B-cyclodextrin–PEG–polyethyleneimine-coated iron oxide NPs	5-FU	L929 and MCF-7	^Citation111
Encapsulation of superparamagnetic Fe3O4	5-FU	7,901 cancer cells	^Citation112
Polyglycerol-coated iron oxide NPs	FA	Human cervical carcinoma cell line	^Citation113
Magnetic mesoporous silica NPs	FA	Cancerous HeLa cells	^Citation114
Folate-decorated cobalt ferrite nanoparticles coated with PEG	FA	HSF 1184 (human skin fibroblast cells) and HeLa (human cervical cancer cell, FAR+)	^Citation115
Iron oxide NPs/hyperbranched polyglycerol	FA	MCF-7 cells	^Citation116
Iron oxide NP-conjugated chitosan-graft-poly(2-dimethylaminoethyl methacrylate)	FA	L929 (mouse fibroblast) cell line, MCF-7 (human breast cancer) cell line, and MDA-MB-231 (human breast cancer) cell line	^Citation117
Iron oxide NPs	FA	MRI detection and hyperthermia treatment of lymph node metastases of prostate cancer	^Citation118
Magnetite@SiO2 nanostructures	FA	Human cervical cancer line	^Citation119
Aminosilane MNPs	FA	Colorectal cancer and an animal model of cancer xenograft	^Citation120
Magnetic NPs/PEG	FA	Human cervix epitheloid carcinoma HeLa cells, human breast carcinoma cells MCF-7 and MDA-MB435	^Citation121
Starch/ZnO-coated iron oxide NPs	FA	Human lymphocytes, HepG2, and MCF-7 cell lines	^Citation122
Fe3O4-ZnO hybrid NPs	FA	Photodynamic therapy, human epithelial colorectal adenocarcinoma (Caco-2) cells	^Citation123
Poly(N-isopropylacrylamide) hydrogel core/superparamagnetic magnetite NPs	FA	Cervical cancer cell line (HeLa)	^Citation124
Polyethylenimine superparamagnetic iron oxide NPs	FA	MRI and PD-L1 siRNA delivery for gastric cancer	^Citation125
Iron oxide NPs/functionalized with FA and rhodamine	FA	Cell proliferation assay on HeLa cells	^Citation126
Bovine serum albumin-coated superparamagnetic γ-Fe2O3 NPs	FA	U251	^Citation127
Amine group immobilized iron oxides, Fe3O4-NH2, attached on the surface of self-assembled triblock copolymer, poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)]	FA	MCF-7	^Citation128
Basic cobalt ferrite (CoFe2O4) particles covalently bonded with a photosensitizer	FA	PC-3	^Citation129
Carboxylated quercetin conjugated to superparamagnetic iron oxide NPs modified by (3-aminopropyl) triethoxysilane, FA, and carboxylated PEG	FA	MCF-7, HeLa, and A549	^Citation130
Superparamagnetic iron oxide functionalized with (3-aminopropyl) triethoxysilane and PEG	FA	U87	^Citation131
Superparamagnetic iron oxide NPs coated with chitosan and FA-conjugated chitosan	FA	MCF-7	^Citation132
FA-targeted iron oxide (Fe3O4) NPs	FA	Human serous ovarian cell line (Skov-3)	^Citation133
Iron oxide NPs/chitosan, FA/loaded with aqueous poorly soluble quercetin	FA	PC-3 and MCF-7	^Citation134
Magnetic mesoporous silica NPs/CuS nanocrystals/photothermal agent/PEG	FA	HeLa	^Citation135
PEGylated PEG bis(carboxymethyl ether)/Fe3O4 NPs	DOX	Cancer therapy	^Citation136
Fe3O4@MoS2 nanocubes	DOX	Human breast cancer xenograft in nude mice	^Citation137
DOX-loaded dendritic-Fe3O4 supramolecular NPs	DOX	Magnetic drug targeting and tumor regression in spheroid murine melanoma model	^Citation138
PEGylated cubic Fe3O4 NPs	DOX	Mouse skin fibrosarcoma (WEHI-164) cells	^Citation139
Magnetite NPs hydrophilized by nonionic surfactant pluronic F127–polyethylene-polypropylene oxide polymer	DOX	LNCaP and PC-3 prostate cancer cell lines	^Citation140
Chitosan-functionalized Fe3O4 NPs	DOX	Ovarian cancer cell (SK-OV-3) and breast cancer cell line (MCF-7)	^Citation141
Fe3O4 NPs coated with poly(N-isopropylacrylamide)	DOX	Human cervical carcinoma cell line, MRI	^Citation142
Iron oxide NPs/DOX-loaded calcium phosphate/arginylglycylaspartic acid	DOX	T24 bladder cancer cells	^Citation143
Sodium alginate-polyvinyl alcohol-bovine serum albumin-coated Fe3O4 NPs	DOX	HepG2 and L02 cells	^Citation144
FA-conjugated PEG-coated MNPs	DOX	HeLa cell line	^Citation145
Fe3O4-inositol hexaphosphate	DOX	MG-63 cell line	^Citation146
Genipin-cross-linked iron (III) oxide/polyetherimide NPs	DOX	HeLa cell line	^Citation147
Polyvinyl alcohol hydrogel grafted by modified Fe3O4 NPs	DOX	DOX delivery	^Citation148
Cucurbit[7]uril-modified iron-oxide NPs	DOX	HeLa cells, MCF-7, A2780, Dox-resistant A2780, and HEK293 cells	^Citation149
Dextran-coated superparamagnetic iron oxide NPs	DOX	Human pancreatic carcinoma cell lines MIA PaCa-2	^Citation150
Dual-targeted NPs loaded with DOX and MNPs	DOX	MCF-7	^Citation151
Superparamagnetic iron oxide NPs	DOX	LO2 and HepG2	^Citation152
Liposome-capped core-shell mesoporous silica-coated superparamagnetic iron oxide NPs	DOX	MCF-7 and U87	^Citation153
Fe3O4 NP-capped mesoporous silica	DOX	HepG2	^Citation154
Superparamagnetic Fe3O4 NPs	DOX	L929 and HeLa	^Citation155
Azobis[N-(2-carboxyethyl)–2-methylpropionamidine]	DOX	MCF-7	^Citation156
Superparamagnetic iron oxide NPs	DOX	U251	^Citation157
Iron oxide@meso-silica NPs	DOX	HeLa cell line	^Citation158
Polyacrylic acid-functionalized Fe3O4 NPs are conjugated with FA through peptide bonding	DOX	HeLa cell line	^Citation159
Fe3O4 encapsulated in inner aqueous phase and hydrophobic drug (curcumin)	DOX	HeLa cell line	^Citation160
PEG carboxyl–poly(ε-caprolactone)-modified MNPs	PTX	Mouse H22 hepatocarcinoma cells (H22), human embryonic kidney cells (HEK293T), and hepatoma carcinoma cell (Hep G2)	^Citation161
Loaded magnetic NPs modified with methoxy PEG-lysine-oleic acid	PTX	Liver, left kidney, and right kidney cell	^Citation162
Fe3O4⋅dopamine-bovine serum albumin/hyaluronic acid	PTX	MRI	^Citation163
TAT peptide-conjugated magnetic PLA-PEG nanocapsules	PTX	Human lung adenocarcinoma epithelial cells A549	^Citation164
Peptide H7K(R2)2-modified, theranostic liposome-superparamagnetic iron oxide NPs	PTX	H7K(R2)2 in MDA-MB-231 cell line, MRI	^Citation165
Fe3O4 NPs into porous isoreticular metal	PTX	HeLa and NIH3T3	^Citation166
Methoxy PEG-poly(d, l-lactide-co-glycolide)(MPEG-PLGA)	PTX	HeLa and A549	^Citation167
Superparamagnetic polymer microcontainers	Dau	pH-sensitive controlled release mechanism	^Citation168
Dau-loaded MNPs	Dau	Human chronic myelogenous leukemia cells (K562 cells)	^Citation169
Magnetic iron oxide NPs coloaded with Dau and 5-bromotetrandrin	Dau	Human leukemia K562/A02 cells	^Citation170
PLA multiwalled carbon nanotubes Fe3O4 composite nanofibers	Dau	Leukemia cancer cells	^Citation171
ZnFe2O4 NPs	Dau	HeLa cells	^Citation172

Abbreviations: Dau, Daunorubicin; DOX, doxorubicin; 5-FU, 5-fluorouracil; FA, folic acid; FAR, folic acid receptor; MNPs, magnetic nanoparticles; NPs, nanoparticles; PEG, polyethylene glycol; PLA, polylactic acid; PTX, paclitaxel.

Figure 6 Controlled release of 5-fluorouracil from CS-PEG/PGS-PEG-coated iron oxide.

Note: Data from Naghizadeh et al.¹⁰⁵

Abbreviations: CS-PEG, chitosan-co-poly(ethylene glycol); PGS-PEG, poly(glycerol sebacate)-co-poly(ethylene glycol).

Figure 7 Smart multifunctional magnetic nanoparticle-based drug delivery system for cancer thermo-chemotherapy and intracellular imaging.

Note: Data from Shen et al.¹⁰⁹

Abbreviations: CHI, chitosan; PNIPAM, poly(N-isopropylacrylamide); TEOS, tetraethyl orthosilicate.

Figure 8 pH-sensitive biocompatible mesoporous magnetic nanoparticles labeled with folic acid as an efficient carrier for controlled anticancer drug delivery.

Note: Data from Avedian et al.¹¹⁴

Abbreviations: MSN, mesoporous silica nanoparticle; PEI, polyethylenimine.

Figure 9 Novel folic acid-conjugated Fe₃O₄-ZnO hybrid nanoparticles for targeted photodynamic therapy.

Note: Data from Kim et al.¹²³

Figure 10 DOX-loaded Fe₃O₄@MoS₂-PEG-2DG nanocubes as a theranostic platform for MRI-guided chemo-photothermal therapy of breast cancer.

Note: Data from Xie et al.¹³⁷

Abbreviations: DOX, doxorubicin; IO, iron oxide; IOMS, Fe₃O₄@molybdenum sulfide; NCs, nanoclusters; PEG, polyethylene glycol; PTT, photothermal therapy.

Figure 11 Sacrificial template-directed fabrication of superparamagnetic polymer microcontainers for the pH-activated controlled release of Dau.

Note: Data from Chatzipavlidis et al.¹⁶⁸

Abbreviations: MNPs, magnetic nanoparticles; PMAA, poly(methacrylic acid); P(MBAAm-co-MAA), poly(N,N0-methylenebis(acrylamide)-comathacrylic acid).

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