Table 1. (a) MRI contrast agents – part I. (b) MRI contrast agents – part II.
Imaging modality | Dye/contrast agent | Means of incorporation | Polymer components | Responsive size change | Responsive imaging property | Formulation method a | Size (nm) | Targeting group | Cells/in vivo work | Therapeutics | Ref. |
(a) | |||||||||||
MRI (Gd-based) | Gd-DOTA | As chemical crosslinkers | PAA chemically crosslinked by DTPA/DOTA crosslinkers | N/A | N/A | A | 54–85 | N/A | N/A | N/A | 20 |
MRI (Gd-based) | Gd-DTPA | Conjugation | Poly(PEGMA)-crosslink by ethylene glycol bisacrylamide | N/A | N/A | B | 10 | N/A | Imaging of blood vessel in mice | N/A | 54 |
MRI (Gd-based) | Gd-DTPA | Electrostatic | PAA + chitosan | pH (zeta potential) | N/A | A + D | 220 | N/A | Imaging of rabbit brain and liver | N/A | 56 |
MRI (Gd-based) + NIR fluorescence | Gd3+ Cy 5.5 | As physical crosslinkers (electrostatic) Conjugation | PEI | N/A | N/A | B | 159 ± 62 | N/A | Imaging of SCC7 tumor of mice | N/A | 55 |
MRI (Fe3O4) | Fe3O4 | Encapsulation | Dextrin-VA-SC16 | N/A | N/A | C | 100 | N/A | Uptake in Murine bone marrow-derived macrophages | N/A | 61 |
MRI (Fe3O4) | Fe3O4 | As core from which polymer matrix was built on | Poly(PEGMA) crosslinked with MBA | N/A | N/A | A + E | 68 | N/A | N/A | Doxorubicin | 63 and 64 |
MRI (Fe3O4) | Fe3O4 | As core from which polymer matrix was built on | Poly(AEM·HCl) crosslinked with MBA | N/A | N/A | A + E | 19 | N/A | Healthy mice | N/A | 65 |
MRI (Fe3O4) | Fe3O4 | Encapsulation | Poly(NIPAAm-co-AA) crosslink by MBA | Temperature and pH | N/A | A + E | 237 (pH 2.7) to 387 (7.6) 25 °C a | N/A | Cytotoxicity on HeLa cells | Doxorubicin | 62 |
MRI (Fe3O4) | Fe3O4 | Encapsulation | Self-assembly of poly(AAc-co-DSA); further coated by (poly(γ-GA-co-γ-GAOSu)-g-PEG-FA) | pH and magnetic hyperthermia | N/A | C + D | 243 (pH 4.7) to 221 (pH 7.4) 20 °C a | Folate acid | Therapeutic efficacy on tumor-bearing mice | Doxorubicin | 77 |
(b) | |||||||||||
MRI (Fe3O4) + UV fluorescence | Fe3O4 fluorescein | Encapsulation Conjugation | PBMA-g-(C12/fluorescein) | N/A | N/A | C | 131–250 | N/A | N/A | N/A | 60 |
MRI (Fe3O4) + UV fluorescence | Fe3O4 fluorescein | Encapsulation Conjugation | pCBMA with disulfide crosslinks | Disulfide: reducing environment | N/A | A + E | 110 | RGD | Uptake in Macrophage cell | Fluorescently labeled dextran (model) | 75 |
MRI (Fe3O4) + NIR fluorescence | Fe3O4 Cy5.5 | Encapsulation Conjugation | Poly(NIPAAm-co-AA) | pH and/temperature | N/A | A + E | 100 (pH 6.8) to 85 (pH 7.4) at 37 °C a | Lactoferrin | Imaging of C6 glioma in rats | N/A | 66 |
MRI (Fe3O4) + UV fluorescence | Fe3O4 Dil | Encapsulation Encapsulation | Self-assembled poly(NIPAAm-co-AA) coated with PEI through electrostatic interaction | Temperature | N/A | C + D | 200 | N/A | Imaging of mice injected with nanogels-loaded hMSC | EPFG expression plasmid | 68 |
MRI (Fe3O4) + UV fluorescence | MnFe2O4 fluorescent Schiff base bond (C N) and double bond (C C) | As core from which polymer graft on Part of polymer matrix | Self-assembled PLL crosslinked by poly-GA | N/A | N/A | B + E | <200 | N/A | Imaging of mice injected with nanogels-loaded DC | N/A | 69 |
MRI (19F) | 19F-TFEMA | Part of polymer matrix | Poly-(DEAMA-co-TFEMA-EGDMA-PEG) crosslinker with ethylene glycol | pH | Signal is turned “On” as pH decrease | A | 63 (pH 7.4) and 90 (pH 6.5) | N/A | N/A | N/A | 72 and 73 |
a Formulation methods: refer to Fig. 1.