International journal of nanomedicine · 2026
Hyaluronic Acid-Modified Redox-Responsive Gambogic Acid Prodrug Micelles for Targeted Therapy of Non-Small Cell Lung Cancer.
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Ke Zhongcheng, Luo Tao, Cheng Xiaoling, Chai Xuwen, Zhu Zitong, Huang Zhusheng, Wang Zhen
Аннотация
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.
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.