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Updated: Sep 12, 2026
A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
Published on: May 4, 2021
An Inhalable Hybrid Nitric Oxide Nanogenerator for Lung Adenocarcinoma Treatment via Bioorthogonal-Activated
Jinglin Zou1, Yuheng Leng1, Chen Zhang2
1Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontier Science Center of the Materials Biology and Dynamic Chemistry, Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai200237, China.
Abstract:
Nitric oxide (NO) holds promise for circumventing resistance to platinum-based chemotherapy by reprogramming the tumor microenvironment (TME) in lung adenocarcinoma (LUAD). However, their further application is greatly hindered by uncontrolled release kinetics and off-target toxicity. Herein, an inhalable NO nanogenerator (10m@FOMs-Cu) that reprograms the TME via specific NO release is developed by encapsulating a biorthogonal-activated NO-cisplatin prodrug into TME-responsive hybrid micelles, allowing for sustained and effective LUAD treatment. The prodrug integrates a Pt-based catalyst with a caged active NO donor within one molecule and is further encapsulated in a disulfide-cross-linked organosilica shell, enabling redox-triggered self-catalytic NO release while minimizing off-target injury to normal tissues. It is verified that nebulized 10m@FOMs-Cu could achieve efficient mucus-extracellular matrix dual barrier penetration to reach the TME, thereby ensuring sustained NO release to potentiate Pt(II)-mediated nuclear damage and Cu(II)/Cu(I)-mediated cuproptosis. This sensitization process reprograms the TME by inducing metabolism-DNA stress feedback, triggering a systemic and durable immune response that confers efficient tumor suppression in orthotopic and rechallenged LUAD. It demonstrates that 10m@FOMs-Cu could serve as a potent and safe nebulized nanomedicine for LUAD therapy and provides insights into designing gas-based nanotherapeutics.
