Year: 2025
Type: article
Abstract: Radiation-induced lung injury (RILI) is a severe side effect associated with radiotherapy for thoracic tumor. RILI is a complex pathological process encompassing early-stage pneumonia and late-stage pulmonary fibrosis, and the process is irreversible. Current research predominantly focuses on early-stage radiation pneumonia, while effective therapeutic approaches for pulmonary fibrosis remain lacking. Therefore, a comprehensive therapeutic strategy addressing both pneumonia and fibrosis is urgently needed for RILI. Micro-nano carriers offer new opportunities for inhalable drug delivery to the lungs, enabling efficient transport across multiple biological barriers for the treatment of pulmonary diseases. Herein, we developed an inhalable microsphere system, RP@BDC, with multilevel responsiveness, designed to meet the size requirements for pulmonary drug delivery and to intervene the entire progression of RILI. Resveratrol and siPAI-1 were chosen as therapeutic agents to inhibit inflammation and fibrosis-related proteins. Chitosan-based nanoparticles (RP@DC) were prepared to enhance drug stability and permeability. CaCO3 biomineralization endowed RP@BDC with acid-responsive particle size transformation properties. RP@BDC microspheres demonstrated excellent responsiveness, releasing drug-loaded nanoparticles in response to the radiation-induced acidic environment, thereby exerting therapeutic effects. In an RILI mouse model, RP@BDC effectively alleviated both radiation-induced inflammation and pulmonary fibrosis by reducing inflammatory factors production and inhibiting plasminogen activator inhibitor 1 (PAI-1) expression. Furthermore, RP@BDC exhibited superior therapeutic efficacy compared to conventional corticosteroids drug. Overall, our multilevel responsive delivery platform offers a promising therapeutic strategy for the comprehensive treatment of RILI.
Source: Nano Research
Authors: Xinlian Wang, Jinhui Lin, Dongtao Yin, Xin Li, Zhichen Lang, Guanghui Zhang, Yueguang Xue, Shilin Li, Xiao Zhang, Bing Han, Fengsheng Li, Ying Liu
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
Awards: G6009739609, G8066649247, G8343671008
OpenAlex ID: W4408042379