Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 22.
doi: 10.1007/s00210-025-04455-7. Online ahead of print.

Dual-targeted protein-coated PLGA nanoparticles for pancreatic cancer therapy: a novel approach using esculetin and curcumin

Ayse Karatug Kacar  1 , Rabia Sak  2 , Ayse Nur Nurdogan  3 , Gamze Ergin Kızılcay  4 , Fatemeh Bahadori  5
Affiliations

Dual-targeted protein-coated PLGA nanoparticles for pancreatic cancer therapy: a novel approach using esculetin and curcumin

Ayse Karatug Kacar et al. Naunyn Schmiedebergs Arch Pharmacol. .

Abstract

The study aimed to investigate the effects of dual-targeted poly-lactic-co-glycolic acid (PLGA) nanoparticles (NP) containing esculetin (ESC) and curcumin (CURC), coated with membrane and cytosolic proteins, isolated from PID-PC (pancreatic islet-derived precursor cells) and MIA PaCa-2 cells, on pancreatic cancer. MIA PaCa-2 cells' viability treated with different combinations of the above-mentioned molecules and proteins was investigated in vitro. The sizes of all formed nanoparticles were determined by the "dynamic light scattering" method. The drug release profile of drug-containing PLGA-NP was examined. Cell death percentages and ROS levels were analyzed. Naked ESC showed an IC50 of 45.226 µg, while PLGA-coated ESC showed no measurable IC50. For CURC, no IC50 was observed in its naked form, but PLGA-CURC induced cell death starting at 6.25 µg. In the PLGA_ESC + CURC group, IC50 values were 75 µg for ESC and 9.375 µg for CURC. PLGA-coated PID-PC cytoplasmic proteins reduced ESC-treated cell viability by 46.42%, while the PLGA-coated MIA PaCa-2 cytoplasmic protein with ESC + CURC was most effective (41.11%). PLGA_ESC was released in 48 h, but protein coating accelerated release to 6 h. CURC showed delayed release, reaching only 30% at 72 h. PID-PC membrane proteins enhanced and prolonged release; MIA PaCa-2 cytoplasmic proteins suppressed it. Necrosis increased in all groups, while apoptosis and ROS decreased except in the CURC-treated groups. The novel membrane and cytosolic protein-coated PLGA-NP designed by our group, for the first time, has provided significant results in the treatment of pancreatic cancer.

Keywords: Curcumin; Esculetin; Pancreatic cancer; Pancreatic islet-derived progenitor cells.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

References

    1. Acharya S, Sahoo SK (2011) PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev 63(3):170–183 - PubMed
    1. Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23(1/A):363–398 - PubMed
    1. Arora R, Sawney S, Saini V, Steffi C, Tiwari M, Saluja D (2016) Esculetin induces antiproliferative and apoptotic response in pancreatic cancer cells by directly binding to KEAP1. Mol Cancer 15:1–15
    1. Arya G, Das M, Sahoo SK (2018) Evaluation of curcumin loaded chitosan/PEG blended PLGA nanoparticles for effective treatment of pancreatic cancer. Biomed Pharmacother 102:555–566 - PubMed
    1. Atwan QS, Al-Ogaidi I (2024) Improving the targeted delivery of curcumin to esophageal cancer cells via a novel formulation of biodegradable lecithin/chitosan nanoparticles with downregulated miR-20a and miR-21 expression. Nanotechnology 35(13):135103

LinkOut - more resources