A MOF-based self-propelled micro/nanomotor for highly efficient and sustainable targeted drug delivery

Abstract

Helicobacter pylori (H. pylori) infection has received tremendous attention due to its progressive injury to the gastric mucosa with a high risk for gastrointestinal diseases such as asymptomatic chronic gastritis, peptic ulcer, and even gastric cancer. H. pylori can create the mucin de-gel and transform their shapes based on the microenvironment so that they could get into the mucus layer easily and thrive in the stomach. However, without the specific characteristics of the bacteria, some pharmaceutical ingredients can hardly reach the lining of the stomach where H. pylori colonize due to the harsh gastric acid environment and the mucosa with high viscosity and elasticity. Considering the increasing prevalence of H. pylori and the high fatality of resulting gastric cancer, finding a more effective and efficient eradication therapy for H. pylori infection is a public health priority. In this thesis, we developed a MOF-based self-propelled micromotor as the modified drug delivery system for H. pylori eradication treatment which could target at stomach mucus layer where the bacteria thrive. The micromotor is composed of PEDOT/Au shell, Zinc engine, R6G@ZIF-8-loaded gelatin and enteric coating. We utilized template electrodeposition method for synthesizing the PEDOT/Au shell and Zn segment. R6G as the model drug was encapsulated by ZIF-8-loaded gelatin and infiltrated into the micromotor for sustainable release. And the enteric polymer was then added at the drug side for the hermetic seal. Once administered, the self-propelled micromotors could propel themselves by generating hydrogen bubbles and the propulsion velocity could reach 60 μm/s. During the propulsion, the model drug in the motor was well-protected from the strong gastric acid with the enteric coating. When they penetrated the firm mucus layer (pH > 6), the enteric cap dissolved and enabled the target drug to be released efficiently. With the high surface area and loading capacity of ZIF-8 particles, the model drug@ZIF-8 showed a flatter release curve and greatly prolonged body retention time (from 12 h to over 2 weeks). The drug capacity and propulsion lifetime can be tuned by adjusting the compartment length. The morphology and compartment distribution have been characterized. The results in vitro showed that the self-propelled micromotor could greatly increase the cell uptake rate (95.8%) compared with the bare model drug (9.3%) with a 150 μm-thick artificial mucus layer. At last, the micromotors were proved to have good biocompatibility and low cytotoxicity (19 μg/ml at cell level). Overall, the proposed MOF-based self-propelled micromotor provides a modified strategy for active transport and targeted drug delivery with sustainable release. It holds considerable promise for a wide range of future applications, including H. pylori, diabetes treatment and oral drug delivery of biomacromolecules.

Date of Award	2022
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Shuhuai YAO (Supervisor)