ArticleInternational journal of nanomedicine2026
Hyaluronic Acid-Modified Redox-Responsive Gambogic Acid Prodrug Micelles for Targeted Therapy of Non-Small Cell Lung Cancer.
Article in International journal of nanomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Gambogic acid (GA) shows potent inhibitory activity against various malignancies. However, achieving precise targeted delivery and spatiotemporal control of drug release at tumor sites remains a significant challenge. This study aimed to develop a hyaluronic acid (HA)-modified, redox-responsive drug delivery system based on a methoxy polyethylene glycol-linked GA prodrug (mPEG-ss-GA). Methods: The amphiphilic prodrug, mPEG-ss-GA, was synthesized by conjugating GA to methoxy polyethylene glycol (mPEG) via a disulfide linkage. Subsequently, it spontaneously self-assembled with HA in an aqueous medium to form HA-modified mPEG-ss-GA micelles (HA/mPEG-ss-GA-M). The physicochemical properties of the micelles, including particle size, zeta potential, morphology, and in vitro release profiles, were systematically characterized. Cellular uptake in human non-small cell lung cancer cells (A549) was visualized using fluorescence microscopy. Furthermore, the in vitro pro-apoptotic effects were quantified using an Annexin V-propidium iodide (PI) binding assay. Finally, the in vivo anti-tumor efficacy was evaluated in a subcutaneous xenograft tumor model. Results: The HA/mPEG-ss-GA-M micelles exhibited an average particle size of 251 nm with a zeta potential of -17.36 mV. The system demonstrated glutathione (GSH)-triggered drug release, with release kinetics that aligned well with the Higuchi model. In vitro studies revealed that HA/mPEG-ss-GA-M significantly enhanced cellular uptake, induced apoptosis, and suppressed cell migration. In vivo experiments showed that HA/mPEG-ss-GA-M achieved a tumor volume inhibition rate of 54.09%, compared to 29.56% for free GA. Conclusion: HA/mPEG-ss-GA-M is a promising drug delivery system for targeted non-small cell lung cancer therapy and offers precise and efficient treatment options.
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