Recently, Prof. Han Heyou’s project team from National Key Laboratory of Agricultural Microbe in HZAU breaks new ground in treating Helicobacter pylori infection with their newly-designed bottle-shaped and silicon-based nanomotors. Their findings are published on the academic magazine Small.
Helicobacter pylori (Hp) is a kind of Gram-negative microaerobes. In 2005, Australian academics Marshall and Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery of Helicobacter pylori and its pathogenesis on peptic ulcer disease. Today, H. pylori infection, found worldwide, has been identified as the single strongest risk factor for epidemiology and gastric malignancy (the fourth most common cancer worldwide), with an approximately 75% risk of causing gastric cancer. Statistics show that more than one million new cases of gastric cancer are diagnosed worldwide each year, with more than 78.3% of these leading to death.
For the treatment of Helicobacter pylori infection, Prof. Han Heyou’s team has ingeniously designed a bottle-shaped and silicon-based nanomotors (Si NBs). These bottle-shaped Si NBs have a hydrophobic outer surface, a hydrophilic inner core, a large chamber and a narrow opening. This unique asymmetric large chamber structure provides good conditions for drug storage, which can be used as a nanomotor for drug delivery.
During the experiments, the drug clarithromycin (CLA), nano-CaO2 and Pt NPs are loaded into the large lumen through amphiphilic interactions. After the nanomotor is delivered to the stomach cavity, CaO2 could temporally and physically alter the local acidic environment by rapidly consuming protons as it advances through the stomach, thus allowing effective neutralisation of the pH in the stomach to avoid reducing the efficacy of the drug and avert chronic toxicity due to the long-term use of proton inhibitors (PPIs). At the same time, energy or fuel from the surrounding environment is converted into kinetic energy, which then drives the nanomotor forward to ensure maximum release and efficacy of the pre-drug.
Experiments have shown that the nanomotors can rapidly consume or temporarily neutralize gastric acid through the chemical reaction of CaO2. The product H2O2 is catalyzed by Pt NPs to break down into large amounts of O2, which is expelled from the nanomotors through narrow openings, driving the nanomotors to move and releasing drugs used to treat H. pylori infections.
The researchers describe that CaO2 reacts with gastric acid to rapidly consume protons and neutralise gastric acid without affecting normal gastric function. This gentle neutralisation method can restore health in a short time and avoid irreversible damage, so nanomotors may be an attractive alternative to PPIs.
In live animal experiments, 15 mg of nanomada can safely and rapidly neutralise gastric acid while releasing pre-drugs to achieve good therapeutic effect without causing acute toxicity. The concentration of H. pylori in mice was 2.6 orders of magnitude lower than that in the control group. Gastric acid of mice returned to normal pH within one day after taking drugs, avoiding disruption of normal gastric function and causing acute toxicity.
The researchers conclude that the acid-driven nanomotor can effectively load clinical doses of drugs and withstand the harsh gastric acid environment to achieve antibacterial effects without the use of PPIs. This result is expected to be developed into a novel and safe gastric treatment as an active device for the treatment of H. pylori infection. Besides, as a novel delivery technology, this motor-driven delivery method is expected to treat a wide range of gastrointestinal diseases.
Source: http://news.hzau.edu.cn/2021/0315/59538.shtml
Translated by: Chen Song
Supervised by: Wang Xiaoyan
