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. 2022 Oct 4;23(19):11793. doi: 10.3390/ijms231911793

Table 3.

Magnetic micelles produced for different applications.

Amphiphilic
Co-Polymer		 MNPs Therapeutic Agent Target Ligand Approach Outcomes Ref.
Imaging
GCPQ Fe3O4 - - MRI
(liver vasculature)
  • -

    High T2 contrast with a spatial resolution for detailed liver vasculature

  • -

    Blood half-life of 28.3 min

  • -

    Preferential accumulation in liver and spleen

 [21]
DSPE-PEG Fe3O4 - - MRI (liver)
  • -

    High T2 contrast up to 3 h in the liver

  • -

    Low toxicity

 [87]
PDLA-b-PEG/PLLA-b-PEG MnFe2O4 (s,c)
MnFe2O4@Fe3O4 		- - MRI
  • -

    Stereocomplexation micelles with improved stability

  • -

    Cubic SPION-loaded micelles with higher T2 contrast imaging than the ones with spherical- or core-shell.

 [49]
P4VP-b-PEG Fe3O4 - - MRI
  • -

    Fabrication of worm-like micelles with a larger number of loaded SPIONs

  • -

    Higher r2 in worm-like micelles than in free SPIONs

  • -

    Shape favors MPM circulation in blood

 [90]
(CA)4-Lys3-PEG Fe3O4 - - MRI
  • -

    Ultra-small size micelles (<40 nm)

  • -

    MRI sensitivity superior to that of free SPIONs

 [79]
WPU-BPLP-WPU Fe3O4 DOX Y1R MRI
  • -

    Darker T2-weighted signal with MPMs

  • -

    Improved blood circulation of iron in MPM (half-live of 69.3 h) than in SPIONs (5.4 h)

 [91]
(CA)2-Lys-(PAsp(DMA)) Fe3O4 - - stem cell labeling
MRI of transplanted NSCs
  • -

    In vivo MRI tracking of NSCs without detrimental effects

  • -

    Cationic micelles (+15 mV) are safer and more efficient for cell labeling than neutral micelles

 [75]
Levan Fe3O4 - - MRI
cell tracking
intracellular magnetic actuators
  • -

    Use of a natural polysaccharide block for improved biocompatibility

  • -

    MRI sensitivity superior to that of free SPIONs

  • -

    Dual mode imaging probes combining SPIONs with quantum dots or gold nanoparticles

 [38]
Theranostic potential
Therapeutics delivery and responsive release
PLGA-PEG Fe3O4 QCT - drug delivery
  • -

    Star-like block polymer

  • -

    Drug loading of 13.4% and loading efficiency of 68%

  • -

    Drug release of 37% after 7 h, and 90% after 72 h

 [77]
PCL-b-PEG Fe3O4 NPX - magnetic drug delivery
  • -

    Smaller micelles (<150 nm) are more efficient for brain-targeting with a higher accumulation of NPX than larger micelles (~240 nm) or free drug

  • -

    Magnetic field of 0.4 T externally applied to direct micelles to the brain

  • -

    Prolonged blood circulation in comparison to free drug

 [76]
Zein-LF Fe3O4 DAS - magnetic drug delivery
pH-release
  • -

    Faster release of DAS at pH 5 > pH 7.4

  • -

    Increased cytotoxicity against MDA-MB-231 cells

  • -

    A magnetic field of 0.5 T significantly reduced the IC50 of DAS-loaded MPM (22.41 µM) to 16.48 µM (IC50 free drug = 30.43 µM)

  • -

    in vitro serum stability and hematocompatibility

 [24]
PCCL-b-PEG Fe3O4 PTX - magnetic drug delivery
magnetic and pH-release
  • -

    High PTX loading

  • -

    Faster release of PTX at pH 6.5 > pH 7.4

  • -

    Low in vitro and in vivo cytotoxicity

  • -

    Higher inhibition of the tumor rate than with a magnetic field of 1.7 T in PTX-loaded MPM (45.23%) than with non-magnetic micelles (30.78%) or free-PTX (7.12%)

  • -

    Effective tumor-specific cell targeting with magnetic field

 [92,93,94]
PCL-b-PEG Fe3O4 QCT - pH-release
  • -

    Faster release of QCT at pH 5.3 > pH 7.4

  • -

    Drug loading of 17.1% and encapsulation efficiency of 95.9%

  • -

    Low toxicity (mitochondrial assays)

 [95]
Octyl-g-HTCC/Octyl-g-PEG-HTCC Fe3O4 PTX - pH-release
  • -

    Faster release of PTX at pH 5.0 > pH 6.5 > pH 7.4

  • -

    Drug loading of 19.71% and encapsulation efficiency of 88.71%

 [22]
P(NIPAAm-co-DMAAm-co-UA) Fe3O4 Hesp - pH-release
  • -

    Faster release of QCT at pH 6.6 > pH 7.4

 [96]
PSar-b-PCys(SO2Et) Fe2O3 Iron (Fe2O3) - redox-release
  • -

    High iron loading (33 wt%)

  • -

    MPM degradation mediated by GSH (10µM–100mM)

  • -

    Induce macrophage activation in vitro and in vivo

 [82]
PCL-b-PEG Fe3O4 DOX - redox-release
  • -

    Use of a simulation method to calculate loading (10%), and encapsulation efficiency (60%)

  • -

    DOX release increased from 40% to 60% with dithiothreitol (10mM)

 [97]
PLA-PEG/PLA-CHI-Spm Fe3O4 siRNA PTX FA
T7 peptide		 dual therapeutics delivery
pH-release
  • -

    Higher release at pH 6 > pH 7.4

  • -

    Encapsulation efficiency: 68.52% (siRNA) and 38.11% (PTX)

  • -

    Lower IC50 (35.4 nM) in MPM combining FA + T7 peptide targeting

 [98]
Imaging/Therapeutics delivery/Combined therapies
PCL-b-PEG Fe3O4 TAM - MRI
drug delivery
  • -

    Drug loading of 8.14% and encapsulation efficiency of 52.19%

 [99]
PS-b-PAA-b-PEG Fe3O4 DC - MRI/optical imaging
drug delivery
  • -

    MNPs synthesized by co-precipitation on the PAA shell

  • -

    Incorporation of a positively charged drug on the PAA shell

 [2]
DSPE-PEG Fe3O4 PTX - MRI
drug delivery
  • -

    SPIONs do not influence cell viability up to 0.8 mg mL−1

  • -

    Good T2-weighted image contrast

  • -

    Significant increase of apoptotic activity in tumor mouse models

 [88]
OCL-Bz-b-PEG Fe3O4 QCT - MRI
magnetic drug delivery
  • -

    Drug loading of 3.5% and encapsulation efficiency of 70%

  • -

    r2 values of 137 mM−1 s−1 (SPIONs) and 246 mM−1 s−1 (MPMs)

  • -

    Magnetic field increases the accumulation of MPMs at the target site

  • -

    Higher toxicity of MPMs to HepG2.2.15 cells than of free drug

  • -

    IC50 is reduced in QCT-loaded MPMs (17.02 µM) compared to the free drug (207.90 µM)

 [84]
PLA-PEG Fe3O4 DOX MRI
pH-release
  • -

    The MPM diameter is SPION concentration dependent

  • -

    The incorporation of SPIONs significantly increases the drug loading from 3.3% to 12.4%, and drug loading efficiency from 19.8% to 90.9%

  • -

    T2 increment in micelles with increased SPION concentration

  • -

    Prolonged circulation half-live and good stability in vivo

 [86]
PCL-b-PEG Fe3O4 DOX PBA optical imaging
magnetic drug delivery
pH-release
  • -

    Higher cell uptake in rod-like MPMs than in the spherical MPMs

  • -

    Improved DOX delivery and accumulation in the tumor using a dual targeting strategy: actuation of a magnetic field of 0.1 T and active targeting (PBA ligand)

  • -

    Higher inhibition rate (83%) of tumor growth in rod MPMs with dual targeting

  • -

    Prolonged circulation half-live (>24 h), and slow blood clearance in rod MPMs with dual targeting

 [85]
PLGA-b-PEI-b-PEG Fe3O4 DOX cRGD MRI-guided therapy
pH-release
  • -

    Faster release of DOX at pH 5.3 > pH 6.0 > pH 7.4

  • -

    Higher inhibition rate of tumor growth with MPMs (50%) compared to the free drug (20%)

  • -

    Negligible harmfulness in vivo

  • -

    Prolonged half-life blood circulation of MPMs (31.2 h) in comparison to the free drug (19.5 h)

 [100]
PAsp(DBA-co-DIP)-b-PEG Fe3O4 DOX - MRI/optical imaging
pH release
  • -

    Faster release of DOX at pH 5.0 > pH 7.4

  • -

    Very low cytotoxicity to HepG2 cells

  • -

    Higher survival time (>70 days) with MPMs in >80% of the animals

  • -

    DiR fluorescence imaging of the tumor tissue

 [1]
PCL-b-PAELG Fe3O4 DOX Gal/Lac MRI
redox release
  • -

    DOX release mediated by GSH (10 mM)

  • -

    Higher r2 values (168.1–259.4 mM−1 s−1) than Feridex® (111.5 mM−1 s−1)

 [83]
PCL-b-HA Fe3O4 DOX - MRI
redox release
  • -

    DOX release mediated by GSH (10 mM) within 12 h

  • -

    DOX loading efficiency of 10% and loading content of 11.3–12.5%

  • -

    Higher cell uptake in HA-SS-PCL than in HA-PCL micelles

  • -

    Lower cytotoxicity than free drug

  • -

    r2 value (221.2 mM−1 s−1)

 [18]
PZLL-g-HA Fe3O4 DOX - MRI
redox release
  • -

    DOX release mediated by GSH (10 mM)

  • -

    DOX loading content of 5.6–6.8%

  • -

    r2 value (231 mM−1 s−1)

  • -

    suitable as HepG2 tumor targeting nanoprobes

 [19]
PEO-b-PPO-b-PEO (Pluronic F127) Zn1.15Fe1.85O4 OA-R837 OVA257-264 MRI/optical imaging
magnetic delivery
redox release
  • -

    Release of OVA + 2 adjuvants (Zn1.15Fe1.85O4 + OA-R837)

  • -

    OVA release mediated by GSH (10 mM)

  • -

    Enhanced delivery of SIM-micelle to lymph node by a magnetic field

  • -

    in vivo upregulation of TNF-α and IFN-γ, and stronger T cell responses in MPMs actuated by a magnetic field.

  • -

    100% survival rate without recurrence for at least 60 days (mice model)

 [55]
PAsp(MEA-co-DIP)-b-PEG Fe3O4 SF AbGPC3 MRI
pH and redox release
  • -

    SF release mediated by pH 5 > pH 7.4, and GSH (10 mM)

  • -

    SF loading content of 3.56%

  • -

    MPMs inhibit tumor growth

  • -

    r2 value is 2.5-fold higher in MPMs than in hydrophilic SPIONs

 [101]
PCL-b-PGA Fe3O4 DOX - MRI
pH and redox release
  • -

    DOX loading content of 10.14%

  • -

    DOX release mediated by pH 5 > pH 7.4, and GSH (2 mM < 10 mM)

  • -

    Selective toxicity to tumor cells

  • -

    r2 value of 192.06 mM−1 s−1

  • -

    100% survival rate during the treatment with MPMs (50% with free DOX)

 [81]
PEG-PU-PCL-PU-PEG Fe3O4 DOX FA MRI
pH- and redox-release
  • -

    DOX loading content of 23%

  • -

    DOX release mediated by pH 6.5 > pH 7.4, and GSH (10 mM)

  • -

    Higher r2 value (89.5 mM−1 s−1) than in SPIONs (54.6 mM−1 s−1)

  • -

    Higher inhibitory effects on tumor growth with magnetic field

 [89]
(CA)2-Lys-(PAsp(DMA)) Fe3O4 siRNA/ASO - MRI tracking of NSCs
neuronal differentiation
  • -

    Enhanced neuronal differentiation of NSCs in vitro and in vivo

  • -

    Improved recovery of the damaged tissue after ischemic stroke

  • -

    Higher r2 value (674.1 mM−1 s−1) than free SPIONs (72.16 mM−1 s−1)

 [12]
CAM-HA (PLL coating) Fe3O4 plasmid (pLuc) - MRI-guided gene delivery
  • -

    In vitro magnetofection of MPMs with pLuc plasmid

 [33]
OAMAM-b-DEX Fe3O4 BPD - MRI
photo release
PDT
  • -

    BPD loading content of 30%

  • -

    Higher r2 value (383 mM−1 s−1) than SPIONs (Feraheme®; 55.26 mM−1 s−1)

  • -

    Slower tumor growth in a 4T1 murine model with MPMs + PDT

 [23]
PCL-b-PEG Mn0.6Zn0.4Fe2O4 - HA MRI
radiotherapy
MHT
  • -

    AMF: 178 kHz, 64.1 A, led to a local temperature variation of +7 °C

  • -

    r2 value of 331 mM−1 s−1

  • -

    Decreased tumor size with combined MHT and radiotherapy

 [54]
C16-g-HA Fe3O4 docetaxel - MRI
photo-thermal therapy
thermo release
  • -

    Docetaxel loading content of 10.9% and encapsulation efficiency of 58.0%

  • -

    r2 value of 158.6 mM−1 s−1

  • -

    Cell uptake increased with magnetic targeting (50 mT)

  • -

    Increased release after irradiation (laser: 808 nm, 10 W cm-2, 10 min)

 [20]
PPI-b-TEGME Fe3O4 DOX - MHT
thermo release
  • -

    DOX loading content of 8.13% and encapsulation efficiency of 55%

  • -

    Increased release with temperature (37 °C < 45 °C) and with AMF (160 kHz, 328 Oe, 5 min exposure)

  • -

    Synergistic effect of thermo-chemotherapy in toxicity of Hepa 1-6 cells

 [8]
PHEP-b-PEG Fe3O4 (c) emodin - MRI
magnetic targeting
MHT
thermo release
  • -

    r2 value of 271 mM−1 s−1

  • -

    Emodin encapsulation efficiency of 73.8%

  • -

    Increased release with temperature (37 °C < 45 °C), and with AMF (35 kA m−1, 10 min exposure)

  • -

    AMF (30 kA, 312 kHz, 10 min) combined with MHT + CHT led to tumor inhibition and prevention of tumor recurrence.

 [31]
P(AAm-co-AN)-g-PEG Fe3O4 DOX A54 hyperthermia (microwave)
thermo- release
  • -

    Microwave: 8 W, 30 min led to a local temperature variation of +13 °C

  • -

    Increased DOX release with microwave (>43 °C)

  • -

    Improved tumor accumulation of MPMs with A54 targeting

  • -

    Anti-tumor efficiency enhanced by microwave hyperthermia

 [102]
P(AAm-co-AN)-g-PEG Fe3O4 DOX - NIR imaging
photo-thermal therapy
thermo release
pH release
  • -

    DOX loading content of 8.7%

  • -

    DOX release mediated by pH 5.5 > pH 6.5 > pH 7.4

  • -

    Increased release after irradiation (laser: 808 nm, 2 W cm−2, 3 min)

  • -

    MPMs elevate temperature in the tumor after NIR irradiation (5 min)

  • -

    Reduced tumor volume after irradiation; damage to tumor cells

 [32]
PHEMA-b-PEG Mn0.6Zn0.4Fe2O4 Pt(IV) - MRI
pH and redox release
magnetic targeting
MHT
  • -

    Pt(IV) loading content of 22.5%

  • -

    Release mediated by pH 5.0 > pH 7.4 (+GSH: 5 µM/1 mM)

  • -

    MHT improved penetration of MPM in tumors

  • -

    Higher tumor inhibition with combined magnetic targeting (180 mT) + MHT (114 kHz, 15.9 kA m−1, 20 min)

 [16]
PAE-b-PEG/DPPC Fe3O4 DOX - MRI/optical/photoacoustic imaging
MHT
photo-thermal therapy
pH- and thermo- release
chemodynamic therapy
  • -

    DOX loading content of 1.082%

  • -

    Release mediated by pH 5.0 > pH 6.5 > pH 7.4, and increased with a magnetic field (500 kHz; 20 kA m−1) + laser (808 nm + 1 W cm-2; + 17 °C) from 44% to 83%

  • -

    Magnetic guidance improved MPMs accumulation in tumors

  • -

    Higher tumor inhibition with MPMs + combinational MHT/CHT/chemodynamic therapy (~94%) in comparison to free drug (54%)

 [103]

The full terms are indicated in the abbreviation section.