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Tumor-Targeted Delivery of Curcumin via Hyaluronic Acid-Functionalized Polymeric Nanoparticles: Characterization and Mechanistic Insights into PI3K/AKT/mTOR Signaling
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DOI：10.1007/s12668-026-02771-7.png)
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Abstract
En 中文
Background: Curcumin is a pleiotropic phytoconstituent with an established anticancer effect that induces its therapeutic action by regulating several oncogenic signaling pathways, including the PI3K/AKT/mTOR pathway. Nevertheless, its clinical translation is still highly limited due to a lack of aqueous solubility, physicochemical instability, rapid systemic clearance, and optimum bioavailability. Objective: A rationally designed hyaluronic acid-based polymeric nanoparticulate system was created in the current study to promote the delivery efficiency and therapeutic potential of curcumin with a focus on its tumor-targeted delivery and regulated release properties. Methods & Characterization: The optimized nanoparticles had a homogenous nanoscale distribution, desirable surface properties, and excellent drug encapsulation. The incorporation of the drug, maintenance of chemical integrity, and conversion of curcumin to a major portion of amorphous form in the polymeric matrix was successful and confirmed through structural and thermal characterization using FTIR, X-ray diffraction, and differential scanning calorimetry. Results: In vitro release tests showed a pH-responsive and sustained drug release profile with increased release under acidic environments, simulating the tumor microenvironment. Ex Vivo permeation studies indicated enhanced membrane penetration and retention over free curcumin, suggesting improved bioavailability and tissue interaction. Molecular docking with PI3K/AKT/mTOR pathway proteins demonstrated strong binding affinity and stable interactions of curcumin with AKT, mTOR, and PI3K, supporting its role as a multi-targeted signaling inhibitor. Conclusion: These results highlight the promise of hyaluronic acid-based polymeric nanoparticles as a powerful nanoplatform to improve curcumin delivery and maximize anticancer effects by modulating key intracellular signaling pathways, offering a strategy to overcome its biopharmaceutical limitations.
Keywords:
Curcumin
Polymeric nanoparticles
Hyaluronic acid
PI3K/AKT/mTOR pathway
Molecular docking
Design-expert optimization
PH-responsive drug release
Ex vivo permeation
Anticancer nanomedicine
Targeted drug delivery
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1.7K
Citations:
3.5K
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