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. 2022 Oct 12;12(20):3567. doi: 10.3390/nano12203567

Table 11.

Examples of Active Targeted Drug Delivery of SIONPs for cancer treatment.

Formula Targeting Agent Drug Shell Target Release Mechanism Procedure Result Ref
Fe3O4/Au/OPSS-PEG-SVA-/PDMAEMA/MTX MTX MTX OPSS-PEG-SVA/PDMAEMA MCF7 and MDA-MB-231 BC cells pHR -Preparing polymer solution via NH2-terminating DMAEMA ((+)ly charged, pHR polymer) (NH2-PDMAEMA)
-Fabricating Fe3O4 via co-precipitation
-Developing Au-Fe3O4 MNPs via standard citrate reduction
-PEGylating MNPs using OPSS-PEG-SVA (MNPs@OPSS-PEG-SVA)
-Adding PDMAEMA onto MNPs@OPSS-PEG-SVA under Ar gas (MNPs@polymer)
-Loading MTX onto MNPs@polymer
-Improved EPR effect
-Prolonged blood circulation
-Safe and CDR at physiological pH
-Improved cytotoxic activity MCF7 and MDAMB231 cell lines
-Potential candidate for passive and active TDD
[276]
Fe3O4/MSN/PEI/ETB FA ETB MS and PEI HeLa cells pHR -Synthesizing of Fe3O4 via co-precipitation
-Coating Fe3O4 NPs with silica to produce (Fe3O4@MSN) using TEOS and CTAB
-Conjugating FA with PEI to produce PEI-FA using FA+DCC+NHS+PEI in coupling reaction
-Preparing Fe3O4@ MSN/PEI-FA, using Fe3O4@MSN+modified PEI-FA+acetic acid
-Loading ETB onto Fe3O4@ MSN/PEI-FA via dissolving ETB in DMSO
-Fe3O4@MSN/PEI-FA-ETB demonstrated higher cytotoxicity effect on HeLa cells compared to Fe3O4@MSN-ETB/PEI (due to lacking TA)
-Non-toxic effect
-TDD and CDR with minimum side effects
-Promising TDD tool for in vivo applications
[277]
Fe3O4/CS/SH/FA/Co 6 FA Co 6 CS HeLa cells RR -Thiolating Fe3O4 and CS separately. (Fe3O4-SH) and (CS-SH)
-Coupling CS-SH with
(1) FA (FA-CS-SH)
(2) RFP (RFP-CS-SH)
-Followed by mixing (1) and (2) in HSO, dispersing Co 6 and ultrasonicating to generate Fe3O4/CS/SH/FA/Co 6
-Higher internalization into HeLa cells compared to the non-targeted MNPs [283]
Fe3O4/PLH−PEG −LiA/FA-PEG/DOX FA DOX Si MCF-7, MDA-MB-231, MCF-10A cells pHR and RR -Preparing MNPs via hydrothermal reaction
-Reacting MNPs with TEOS to produce Fe3O4@SiO2
-Preparing MPS coating (using C18TMS), to produce Fe3O4@SiO2@MSiO2
-Loading Dox onto Fe3O4@SiO2@MSiO2
-Preparing polymer (PLH−PEG− NH2) using coupling reaction (EDC and NHS reagents)
-Connecting LiA to PLH−PEG−NH2 using DCC coupling reagent to produce PLH−PEG−LiA polymer
-Synthesizing FA−PEG−NH2 via coupling reaction
-Elipsoidal-shaped MNPsenhanced uptake and cell morbidity compared to the non-targeted NPs against BC cell
-Substantial increase in DOX release in the presence of 10 mM GSH at pH 5.5 (97.1%) as compared to pH 7.4 (31.7%) within 24 h
[284]
Fe3O4/SiO2/MUC1 Apt/DOX MUC1 Apt DOX SiO2 MCF-7 and MDA-MB-231 BC cells pHR -Preparing SIONP using thermal decomposition
-Developing SIONPs@SiO2-NH2 using TEOS and APTEs in the presence of CTAB
-Fabricating SIONPs@SiO2-COOH via reacting SIONPs@SiO2-NH2 with succinic anhydrate in DMF
-Anchoring DOX onto SIONP-SiO2-COOH
-Decorating SIONP@SiO2-COOH/DOX by MUC1 Apt
-Labelling SIONP@SiO2/DOX/MUC1 Apt with fluorophore using PBS and FITC
-Remarkably high drug release in acidic TME
-Potential multi-modal candidate used for diagnosis and treatment of MUC1 overexpressed malignant cells.
-Higher toxicity and internalization by MUC1 expressing MCF-7 cells
[287]
Fe3O4/PEI/HPhBA/DOX PhBA DOX PEI U-87 MG pHR -Functionalizing Fe3O4 by NH2 groups (Fe3O4-NH2)
-Preparing NH2 groups of Fe3O4-NH2 by PEI
-Reacting with PhBA to fabricate HPhBA-MNPs
-Increased therapeutic effect on U-87 MG malignant glioma cells.
-Improved cellular uptake and CDR
[288]
Fe3O4/GO multi/Lf DOX LF DOX -GO C6 glioma cells pHR -Encapsulating Fe3O4 by GO (GO/Fe3O4)
-Functionalizing by LF via click chemistry for TDD
-Loading DOX onto MNPs
-Intracellular delivery efficiency
-Increased cytotoxicity against C6 glioma cells
[289]
Fe3O4/TMSMA/QDMAMEA/Aly-Imz/CD/MTX MTX MTX β-CD Saos-2 bone cancer cells pHR -Grafting β-CD onto Aly-Imz (via reflux-coprecipitation)
-Preparing CMNPs via FRPR (using β-CD/Aly-Imz/QDMAME/TMSMA in DMSO under N2), followed by co-precipitation
-Loading with MTX for TDD to Saos-2 cells
-Successful pH-responsive characteristics
-Increased cytotoxicity,
-Enhanced cellular uptake in Saos-2 cells
-No major cytotoxicity effects on HRBCs.
[290]
Fe3O4/CS/PNIPAAm-Co-IA/MTX/ETB MTX ETB CS-NIPAAm-IA OVCAR-3 cells pHR and TR -Modifying CS with SDS and MaA, (generating polymerizable organo-soluble precursor)
-Grafting NIPAAm and IA (TR and pHR monomers) onto CS via FRPR (co-polymerization)
-synthesizing MNPs via co-precipitation
-Developing MNPs@CSC
-Activating MTX via coupling reaction (using EDC and NHS reagents)
-Conjugating MTX with MNPs@CSC (producing MNPs@CSC-MTX)
-Loading ETB onto MNPs@CSC-MTX (producing MNPs@CSC-MTX-ETB)
-spherical-shaped MNPs
-High loading efficiency for ETB.
-Increased cytotoxicity and
-Higher cellular uptake of MTX, by FR-positive cells
-TDD and improved drug release
-Potential theranostic nano-system for the targeted imaging/treatment of solid tumors, e.g., ovarian
[291]
O-CMCS-Fe3O4-PEM PEM PEM O-CMCS A549-luc-C8 and CRL5807 cell pHR -Improving CS solubility by O-CM (O-CMCS)
-Encapsulating O-CMCS by Fe3O4 to produce MNPs (O-CMCS MNPs)
-Loading PEM onto O-CMCS MNPs
-Highly promising therapy for NSCL carcinoma [292]
Fe3O4/MUC-1/PEG//DOX MUC-1 Apt DOX PEG MDA-MB-231 and MCF-7 cells pHR -PEGlayting SIONPs
-Decorating by MUC1-Apt
-Higher uptake as compared to non-specific targeted NPs,
-Increased death rate in MCF-7 cells
[293]

Folic Acid (FA), Targeted drug delivery (TDD), Hyperthermia (HT), Polyethylene glycol (PEG), Cationic magnetic nanoparticles (CMNP), Allyl imidazole (Aly-Imz), Free radical polymerization reaction (FRPR), Dimethyl sulfoxide (DMSO), Human red blood cells (HRBC), Orthopyridyl disulfide-poly(ethylene glycol)-succinimidyl valerate (OPSS-PEG-SVA), poly (butylene adipate) PBA, Dimethyl formamide (DMF), Temozolomide (TMZ), 3-(Trimethoxysilyl) propyl methacrylate (TMSMA), Mesoporous nano-cage (MPNCs), Quaternized ammonium alkyl halide N,N-dimethylaminoethyl methacrylate (QDMAMEA), Phenylboronic acid (PhBA), hyperbranched phenylboronic acid (HPhBA), Targeting Agent (TA), β-Cyclodextrin (β-CD), Positively ((+)ly), Methotrexate (MTX), Oleic acid (OlA), 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)] (DSPE-PEG-MAL), Lactoferrin (LF), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (1,2-DPPC), Perflenapent (PFP), Fingolimod (FTY720), Poly(N-isopropylacrylamide) (PNIPAAm), Itaconic acid (IA), Ovarian cancer cells (OCC), Sodium dodecyl sulfate (SDS), Maleic acid anhydride (MaA), Chitosan co-polymer (CSC), MUC-1 aptamer (MUC-1 Apt), Tetra-ethyl ortho-silicate (TEOS), Phosphate-buffered saline (PBS), Fluorescein isothiocyanate (FITC) octadecyltrimethoxysilane (C18TMS), Poly-L-histidine (PLH), Lipoic acid (LiA), 3-aminopropyltriethoxysilane (APTES), Cetyltrimethylammonium bromide (CTAB), Red fluorescent probes (RFP), Hydroxy silicon oil (HSO), Coumarin 6 (Co 6), Redox Responsive (RR), Pemetrexed (PMX), O-Carboxymethyl chitosan (O-CMCS), Non-small-cell-lung (NSCL).