Harnessing synergistic SN38/quercetin nanomicelles via nebulized inhalation for enhanced lung cancer treatment.

Authors

Xudong Fan, Jingming Luo, XiaoQian Tang, Jie Zhang, Ruoying Zhang, Xinjun Cai

Published in

Drug delivery and translational research. Aug 03, 2026. Epub Aug 03, 2026.

Abstract

Lung cancer remains a leading cause of cancer-related mortality worldwide, while the clinical utility of irinotecan-derived therapies is often constrained by poor drug solubility, suboptimal biodistribution, and systemic toxicity. To overcome these limitations, we developed polymeric nanomicelles co-loading 7-Ethyl-10-hydroxycamptothecin (SN38), the active metabolite of irinotecan, and quercetin, a naturally occurring flavonoid with intrinsic antitumor activity, for nebulized inhalation delivery. The dual-drug nanomicelles (SN38/QU-PPM) were prepared by nanoprecipitation and exhibited a uniform particle size distribution, excellent stability, and pH-responsive drug release under acidic conditions. In vitro studies demonstrated that quercetin co-loading enhanced cellular uptake of the nanomicelles and promoted intracellular accumulation of SN38, resulting in significantly greater cytotoxicity against LLC-Luc lung cancer cells compared with SN38-loaded nanomicelles alone. In an orthotopic lung cancer model, nebulized inhalation of SN38/QU-PPM achieved a 3.33-fold higher pulmonary SN38 concentration than intravenous administration at 24 h. Nebulized SN38/QU-PPM also exhibited superior antitumor efficacy, achieving a tumor inhibition rate of 80.7%, accompanied by increased apoptosis, reduced tumor cell proliferation. Histopathological examination and serum biochemical analyses indicated no apparent treatment-related abnormalities following inhalation administration. Collectively, SN38/QU-PPM delivered via nebulized inhalation represents an effective lung-targeted drug delivery strategy that enhances local drug exposure and potentiates the antitumor efficacy of SN38. This dual-drug nanomicelle platform holds considerable promise for the treatment of lung cancer through nebulized inhalation therapy.

PMID:
42547691
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.