Self‐Propelled PLGA Micromotor with Chemotactic Response to Inflammation

Abstract

Local drug delivery systems have recently been developed for multiple diseases that have the requirements of site‐specific actions, prolonged delivery periods, and decreased drug dosage to reduce undesirable side effects. The challenge for such systems is to achieve directional and precise delivery in inaccessible narrow lesions, such as periodontal pockets or root canals in deeper portions of the dentinal tubules. The primary strategy to tackle this challenge is fabricating a smart tracking delivery system. Here, drug‐loaded biodegradable micromotors showing self‐propelled directional movement along a hydrogen peroxide concentration gradient produced by phorbol esters‐stimulated macrophages are reported. The drug‐loaded poly(lactic‐co‐glycolic acid) micromotors with asymmetric coverage of enzyme (patch‐like enzyme distribution) are prepared by electrospraying and postfunctionalized with catalase via 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide coupling. Doxycycline, a common drug for the treatment of periodontal disease, is selected as a model drug, and the release study by high‐performance liquid chromatography is shown that both the postfunctionalization step and the presence of hydrogen peroxide have no negative influence on drug release profiles. The movement behavior in the presence of hydrogen peroxide is confirmed by nanoparticle tracking analysis. An in vitro model is designed and confirmed the response efficiency and directional control of the micromotors toward phorbol esters‐stimulated macrophages.

Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT

“…(1) In this regard, micro-and nanomotors have demonstrated enhanced targeting properties (2)(3)(4)(5) and superior drug delivery efficiency compared to passive particles. (6)(7)(8)(9) Additionally, they outperform traditional nanoparticles in terms of penetration into biological material, such as mucus, (10)(11)(12)(13) cells (14)(15)(16) or spheroids. (4,17) Particularly, using enzymes as biocatalysts is emerging as an elegant approach when designing self-propelled particles, due Nanomotors were prepared by synthesizing mesoporous silica nanoparticles (MSNPs) using a modification of the Stöber method (see experimental section for details), (46) and their surface was modified with amine groups by attaching aminopropyltriethoxysilane 7 temperature) of the nanomotors with the prosthetic group.…”

Biocatalytic Micro‐ and Nanomotors

“…Recently, Wilson et al. reported on CAT‐powered biodegradable poly(lactic‐ co ‐glycolic acid) micromotors, which moved in response to a hydrogen peroxide concentration gradient, for the delivery of a drug for the treatment of periodontal disease . The chemotactic self‐propulsion of micromotors was studied in an in vitro model of inflammatory periodontitis with a phorbol ester stimulated macrophage cell.…”

Enzyme catalysis powered micro/nanomotors for biomedical applications

“…The micromotors were powered with catalase enzymes that could induce motion and provide directional motion in the presence of a H 2 O 2 gradient produced by macrophage cells incubated with phorbol-12-myristate-13acetate. 100 All the above examples showcase the advantages of polymer based MNMs powered by enzymes and warrant further investigation for their biomedical application.…”

“…2b). 100 We believe that the use of chemotaxis behavior for enzyme powered MNMs can be an ideal approach for developing the next generation of nanocarriers for biomedical applications, however, mechanistic studies based on EPMs are necessary for further understanding of these motors in particular when placed in biological environments.…”

“…(b) Schematic overview of the chemotactic model. Raw 264.7 cells before and after being triggered by PMA (green: actin cytoskeleton, blue: cell nuclei) 100. (c) Schematics of the proposed mechanisms of asymmetric polymersome chemotaxis, which consist of alternative running and reorientation events.…”