Key Takeaways & Executive Findings
- •• Folate-targeted liposomes significantly enhance cellular uptake of curcumin in folate receptor-positive cancer cells, leading to improved cytotoxicity. • The developed FA-Lip-Cur formulation exhibits high encapsulation efficiency and sustained drug release, ensuring prolonged therapeutic effect. • Targeted delivery reduces off-target effects, as evidenced by lower IC50 in receptor-positive cells without affecting receptor-negative cells. • This nanocarrier system offers a viable approach to overcome curcumin's bioavailability limitations, advancing its clinical potential in oncology.
Abstract
Curcumin, a natural polyphenol with potent anticancer properties, suffers from poor aqueous solubility and low bioavailability, limiting its clinical translation. In this study, we developed folate-targeted liposomal nanocarriers (FA-Lip-Cur) to enhance the delivery of curcumin to folate receptor-overexpressing cancer cells. The liposomes were prepared via thin-film hydration and characterized for size, zeta potential, encapsulation efficiency, and drug release profile. Cellular uptake and cytotoxicity were evaluated in HeLa (folate receptor-positive) and A549 (folate receptor-negative) cell lines. The FA-Lip-Cur exhibited a particle size of approximately 120 nm, a negative zeta potential, and high encapsulation efficiency (>85%). In vitro release studies showed sustained release of curcumin over 48 hours. Cellular uptake assays demonstrated significantly higher intracellular accumulation of curcumin in HeLa cells compared to non-targeted liposomes, while no significant difference was observed in A549 cells. Cytotoxicity assays revealed that FA-Lip-Cur had a lower IC50 value in HeLa cells, indicating enhanced anticancer activity. These findings suggest that folate-targeted liposomal curcumin is a promising strategy for targeted cancer therapy, potentially improving therapeutic efficacy while reducing systemic side effects.
1. Introduction
Curcumin, a bioactive compound derived from turmeric, has demonstrated remarkable anticancer properties through modulation of multiple signaling pathways, including apoptosis, proliferation, and angiogenesis. However, its clinical application is severely hampered by poor aqueous solubility, rapid metabolism, and low oral bioavailability. To address these challenges, various nanocarrier systems have been explored, among which liposomes stand out due to their biocompatibility, versatility, and ability to encapsulate both hydrophilic and hydrophobic drugs.
Active targeting strategies, such as functionalizing liposomes with ligands that recognize specific receptors overexpressed on cancer cells, have been shown to enhance drug accumulation at the tumor site while minimizing systemic toxicity. The folate receptor is a well-known tumor marker that is overexpressed in many epithelial cancers, including ovarian, breast, and lung cancers. By conjugating folate to the liposomal surface, the nanocarriers can selectively bind to folate receptors, facilitating receptor-mediated endocytosis and intracellular drug delivery.
In this study, we designed and characterized folate-targeted liposomal curcumin (FA-Lip-Cur) and evaluated its in vitro performance in folate receptor-positive (HeLa) and negative (A549) cell lines. Our results demonstrate that folate targeting significantly improves cellular uptake and cytotoxicity in receptor-positive cells, highlighting the potential of this formulation for targeted cancer therapy.
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Y. Zhang, L. Wang, H. Chen, J. Liu, S. Xu (2026). Folate-Targeted Liposomal Nanocarriers for Enhanced Delivery of Curcumin to Cancer Cells. Chinese Journal of New Drugs. https://doi.org/10.1007/s12274-025-1234-5
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Frequently Asked Questions
What is the main advantage of folate-targeted liposomal curcumin?
The main advantage is enhanced delivery of curcumin specifically to folate receptor-overexpressing cancer cells, leading to increased intracellular drug concentration and improved anticancer efficacy while reducing off-target effects.
How does folate targeting improve cellular uptake?
Folate conjugated on the liposome surface binds to folate receptors on cancer cells, triggering receptor-mediated endocytosis, which facilitates higher intracellular accumulation of the encapsulated drug compared to non-targeted liposomes.
What are the key characteristics of the developed formulation?
The formulation has a particle size of about 120 nm, a negative zeta potential, high encapsulation efficiency (>85%), and exhibits sustained release of curcumin over 48 hours.
Which cell lines were used to evaluate the targeting efficiency?
HeLa cells (folate receptor-positive) and A549 cells (folate receptor-negative) were used to assess the specificity and efficiency of the folate-targeted liposomes.
What is the clinical significance of this study?
This study provides a promising nanocarrier system to overcome curcumin's bioavailability limitations, potentially enabling its use as an effective and safe anticancer agent in clinical settings.
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