Magnetic Microrobots with Folate Targeting for Drug Delivery

Abstract

Untethered microrobots can be used for cargo delivery (e.g., drug molecules, stem cells, and genes) targeting designated areas. However, it is not enough to just reach the lesion site, as some drugs can only play the best therapeutic effect within the cells. To this end, folic acid (FA) was introduced into microrobots in this work as a key to mediate endocytosis of drugs into cells. The microrobots here were fabricated with biodegradable gelatin methacryloyl (GelMA) and modified with magnetic metal-organic framework (MOF). The porous structure of MOF and the hydrogel network of polymerized GelMA were used for the loading of enough FA and anticancer drug doxorubicin (DOX) respectively. Utilizing the magnetic property of magnetic MOF, these microrobots can gather around the lesion site with the navigation of magnetic fields. The combination effects of FA targeting and magnetic navigation substantially improve the anticancer efficiency of these microrobots. The result shows that the cancer cells inhibition rate of microrobots with FA can be up to 93%, while that of the ones without FA was only 78%. The introduction of FA is a useful method to improve the drug transportation ability of microrobots, providing a meaningful reference for further research.

Fig. 1.

The illustration of magnetically controlled ABF microrobots for folate-targeted cancer therapy.

Fig. 2.

Schematic illustration of the Y-shape microchannel fabrication process. (A) A layer of SU-8 coated on a glass substrate. (B) UV polymerization of SU-8 with a Y-shape photomask. (C) Development of photopolymerized SU-8. (D) The obtained SU-8 Y-shape pattern. (E) Heating of PDMS to fabricate the microchannel. (F) The obtained Y-shape PDMS microchannel.

Fig. 3.

(A and B) The optical images of ABF and ABF-MOF(FA), respectively. (C) The optical image and SEM image of ABF-MOF(FA)-DOX. (D and E) The SEM image of MOF and MOF(FA). (F) XRD analysis of MOF and MOF(FA), respectively. (G) Magnetization curves of soft magnetic MOF and MOF(FA). (H) Collection of MOF (left) and MOF(FA) (right) with a magnet. (I) Fluorescence emission spectra of MOF(FA), MOF, and pure FA.

Fig. 4.

Drug release curve of ABF-DOX at 37 °C and pH 5.3.

Fig. 5.

Viability analysis of MCF-7 cells treated with different samples for 24 and 48 h.

Fig. 6.

Live/dead staining images of MCF-7 cells treated with ABF-MOF(FA), ABF-MOF-DOX, and ABF-MOF(FA)-DOX for 24 and 48 h. Scale bar, 200 μm. PI, propidium iodide.

Fig. 7.

(A and B) The swimming trajectory images of a ABF-MOF(FA)-DOX microrobot was driven by a rotating magnetic field in the microchannel and the cell environment. Scale bar, 200 μm.

Fig. 8.

(A) A photo of the Y-shape microchannel. (B) A snapshot of microrobots being navigated in the Y-shape microchannel. (C and D) Bright-light images of hole 1 and hole 2 after the entire 48-h incubation, respectively. (E and F) Fluorescence images of dead cells in hole 1 and hole 2 after the entire 48-h incubation, respectively.