3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling

Abstract

Miniaturization of interventional medical devices can leverage minimally invasive technologiesby enabling operational resolution at cellular length scales with high precision and repeatability.Untethered micron-scale mobile robots can realize this by navigating and performing in hard-toreach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 µm length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibodytagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.

3D‐Printed Microrobots with Integrated Structural Color for Identification and Tracking

“…Complex tubular structures, as well as single and double conical structures of varying roughness and geometry, fabricated using 3D‐printing processes proved the versatility of the present method, and further demonstrated 3D chemical patterning of very specific areas of 3D‐printed structures for encoded functionality . Advanced biodegradable microswimmers for environmental applications, as well as target cell labeling and drug delivery tasks, have recently been reported, exploring biocompatible microrobotics with theranostic capabilities …”

Mobile Microrobots for Active Therapeutic Delivery

“…The metastatic cancer marker MMP‐2 boosted the cargo release by causing the drug‐carrier microswimmer body to swell. Additionally, the surface‐modified nanoparticles that provided the magnetic thrust could diffuse around upon the enzymatic degradation of the microrobots to label cells for potential medical diagnosis …”

Roads to Smart Artificial Microswimmers

“…More recently, Ceylan et al [163] designed a 3D-printed microswimmer that self-destructs while delivering its cargo as a response to pathological markers in its microenvironment. The hydrogel-based, enzymatically degradable microswimmer swells and decomposes at high concentrations of matrix metalloproteinase-2 (MMP-2) enzyme, whose overexpression is a potential biomarker for certain types of cancers such as colorectal cancer.…”