A Multidrug Delivery Microrobot for the Synergistic Treatment of Cancer

Abstract

Multidrug combination therapy provides an effective strategy for malignant tumor treatment. This paper presents the development of a biodegradable microrobot for on‐demand multidrug delivery. By combining magnetic targeting transportation with tumor therapy, it is hypothesized that loading multiple drugs on different regions of a single magnetic microrobot can enhance a synergistic effect for cancer treatment. The synergistic effect of using two drugs together is greater than that of using each drug separately. Here, a 3D‐printed microrobot inspired by the fish structure with three hydrogel components: skeleton, head, and body structures is demonstrated. Made of iron oxide (Fe3O4) nanoparticles embedded in poly(ethylene glycol) diacrylate (PEGDA), the skeleton can respond to magnetic fields for microrobot actuation and drug‐targeted delivery. The drug storage structures, head, and body, made by biodegradable gelatin methacryloyl (GelMA) exhibit enzyme‐responsive cargo release. The multidrug delivery microrobots carrying acetylsalicylic acid (ASA) and doxorubicin (DOX) in drug storage structures, respectively, exhibit the excellent synergistic effects of ASA and DOX by accelerating HeLa cell apoptosis and inhibiting HeLa cell metastasis. In vivo studies indicate that the microrobots improve the efficiency of tumor inhibition and induce a response to anti‐angiogenesis. The versatile multidrug delivery microrobot conceptualized here provides a way for developing effective combination therapy for cancer.

Direct laser writing-enabled 3D printing strategies for microfluidic applications

“…6a) to reduce refraction-related aberrations to the laser. [193][194][195] Thus, the laser must pass through several different mediums to ultimately initiate photopolymerization at the voxel site: (i) the objective lens, (ii) the immersion oil, (iii) the substrate, and then (iv) the photomaterial of interest, which in some cases includes through previously polymerized microstructures (Fig. 6b).…”

A Review of Soft Microrobots: Material, Fabrication, and Actuation

“…Biofriendly materials can interact harmoniously with biological systems, promoting safe use in various medical scenarios. Soft microrobots made of them can be programmed to perform specific tasks such as drug delivery, [35,39] biosensor, and [95] tissue engineering. [96] Based on detailed properties, biofriendly materials can be further classified into biocompatible and biodegradable materials.…”

“…So far, hydrogels, [38,39] elastomers, [40] rubbers, [41] other soft polymers, [22,42] and live organisms [43] have been used to make soft microrobots. Appropriate fabrication methods should be selected according to the physicochemical properties of materials and application requirements.…”

Current Biomedical Applications of 3D-Printed Hydrogels

“…PEG and polyethylene glycol diacrylate (PEGDA) have been incorporated in hydrogels for engineering biliary [68], bone [69], cartilage [70,71], nervous [72][73][74], and vascular tissues [75]. It has also been used to fabricate 3D-printed cell culture scaffolds [25,76,77] and novel delivery systems [78,79]. PVA is another hydrophilic polymer that is commonly used to fabricate hydrogels.…”

“…On the other hand, iron oxide nanoparticles have been recently incorporated into a chitosan-based hydrogel to create untethered milli-grippers that could grasp and release cargos under the influence of an applied magnetic field [113]. Likewise, iron oxide nanoparticles embedded in PEGDA have been used to fabricate the skeleton of microrobots that can respond to magnetic fields for actuation and drug delivery [78]. Metallic microparticles and nanoparticles may also be incorporated into 3D-printed hydrogels to provide responsiveness to stimuli other than magnetic fields, such as light and ultrasound.…”