Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

Abstract

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.

Smart Shape‐Memory Polymeric String for the Contraction of Blood Vessels in Fetal Surgery of Sacrococcygeal Teratoma

“…Magnetic nanoparticles (MNPs) have become ubiquitous in biomedical applications such as therapeutic microbots, [42] hyperthermia therapy for cancer, [43,44] and SARS-CoV-2 detection strips [45] owning to their great colloidal stability, biocompatibility and thermal property. [46] In our lab, we have developed a MNPs-incorporating linear PCL-based SMP for simultaneous thermo-chemotherapy.…”

Microrobots for Targeted Delivery and Therapy in Digestive System

“…Despite the esophagus can be easily accessed through oral administration, targeted therapies for esophageal cancer face the challenge of the fluid gravity factor due to rapid transit times and low uptake as well as weak adhesion of the drugs. Inspired by marine mussels, Choi et al 100 reported a magnetically guidable drug vehicles that were capable of strongly adhering to target sites using a bioengineered mussel adhesive protein to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions (Figure 8f). For mice without an applied magnetic field around the anterior neck tissue the particles (drug vehicles) were detected in the lower GI track after oral administration.…”

“…(f) Protein-based adhesive soft microrobots, that can overcome the short dwell time of drugs in the esophagus to enable targeted drug delivery. Reproduced with permission from ref . Copyright 2021 Wiley-VCH.…”

“…Schematic illustration of miniature robots based on self-propulsion and magnetic field locomotion mechanisms (inner circle) that are tracked and localized with various types of imaging modalities (middle circle) for a variety of applications in the GI tract, including gastric ulcer therapy, stomach acid neutralization, esophageal cancer therapy, oral antiviral vaccines, treatment of Helicobacter pylori infection, active penetration of mucin gels, and prolonging of retention time for sustained drug release (outer circle). Figure created by the authors with the insets reproduced from refs and − . Stomach acid neutralization.…”

Bioinspired oral delivery devices

“…Oral delivery refers to the route of pharmaceutical absorption through the digestive tract for local or systemic therapy. Drug formulations are orally delivered to reach the buccal cavity 1 , oesophagus 2 , stomach 3 and intestine 4,5 . As one of the most common drug delivery methods, oral delivery offers a non-invasive, low-cost route of administration with high drug versatility and patient compliance 6,7 (Fig.…”