01
The Cancer That is Not Cancer
Pulmonary fibrosis is a chronic, progressive, and fatal interstitial lung disease characterized by scarring and hardening of lung tissue or leather-like changes, which prevent normal lung expansion, impede oxygen entry into the body, cause dyspnea, and ultimately often lead to death from respiratory failure.
Pulmonary fibrosis is mainly classified into idiopathic pulmonary fibrosis, secondary pulmonary fibrosis and hereditary pulmonary fibrosis.
Idiopathic pulmonary fibrosis is the most common type, also known as “loofah lung”, and is one of the most aggressive interstitial lung diseases; approximately 14 to 43 per 100,000 people are affected, with an unclear pathogenesis and limited treatment options.
02
New Breakthrough in Pulmonary Fibrosis
Research on pulmonary gene therapy indicates that nebulized RNA therapy is highly suitable for treating respiratory diseases, particularly pulmonary fibrosis (PF), but achieving effective delivery remains challenging. To address this, researchers from the University of California, the University of Macau, and the University of Hong Kong jointly conducted related studies.
Recently, the study results were successfully published in the international top-tier journal Science Advances under the title “Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis”[1].
Schematic of the aerosol inhalation system
In this study, researchers used Asclepius Meditec hydrogen–oxygen generators to facilitate nebulized LNP penetration across the mucus barrier and designed an aerosol inhalation system consisting of a vibrating mesh nebulizer to aerosolize lipid nanoparticles (LNPs), and a central chamber connected to six mouse restrainers to control low-dose LNP administration at the desired hydrogen concentration.
The researchers further developed hybrid lipid nanoparticles (HNPs) by hybridizing a pH-dependent charge-reversal lipid membrane with apoptotic T-cell membranes to enhance endosomal escape and trigger macrophages to produce cell growth factors for lung repair.
Nanoparticle formulation analysis in lung tissue
The results showed that 72 hours after inhalation of hydrogenated HNPs, strong fluorescent signals were still detectable in lung tissue, indicating excellent pulmonary retention following nebulization via the aerosol inhalation device. After inhalation of hydrogenated HNPs, permeability was enhanced, enabling effective deposition into deeper alveoli and precise targeting.
By effectively delivering HNPs/TGFβ1 siRNA into the lungs, hydrogenated HNPs provide evidence for potential therapeutic effects in reversing pulmonary fibrosis (PF), representing a major breakthrough!
03
Hydrogen as a Drug Delivery Assistant
In the above study, hydrogen exhibited lower viscosity and a smaller Reynolds number, resulting in high shear forces that reduced aerodynamic barriers and enabled penetration into deeper regions.
Hydrogen supplied by the Asclepius Meditec hydrogen–oxygen generator disrupts NP–mucus interactions, enhances deposition of aerosolized HNP/TGFβ1 siRNA within fibrotic lung lesions, effectively blocks fibrotic signaling pathways, and provides a clinically feasible strategy against PF.
These properties of hydrogen may also benefit other mucus-obstructive pulmonary diseases, including chronic obstructive pulmonary disease (COPD)[2], asthma[3], and pulmonary fibrosis[4].
In addition, in pharmaceutical R&D, rare diseases represent a critical field; by early 2024, the number of rare-disease drugs under development reached 7,191, representing a 7.6% increase year over year. Most rare-disease programs remain at the preclinical stage. Hydrogen may facilitate drug delivery and potentially enhance the effectiveness of clinical trials for these rare-disease therapies.
In summary, hydrogen, as an adjunct to drug delivery systems, holds substantial potential value.
References:
[1] Liu C, Tian X, Wang Z, Mak JCW, Mao S, Liu TM, Zheng Y. Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis. Sci Adv. 2025 Apr 18;11(16):eadt2752.
[2] Zheng et al. Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial. Respir Res. 2021 May 13;22(1):149
[3] Huang et al. Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model. International Immunopharmacology. 2019 Sep;74:105646
[4] Gao et al. Hydrogen inhalation alleviates pulmonary fibrosis by inhibiting the TGF-β1 pathway. Experimental Physiology. Exp Physiol. 2019 Dec;
