Delivery of acetogenin-enriched Annona muricata Linn leaf extract by folic acid-conjugated and triphenylphosphonium-conjugated poly(glycerol adipate) nanoparticles to enhance toxicity against ovarian cancer cells

The study demonstrated the fabrication of new poly(glycerol adipate) (PGA) nanoparticles decorated with folic acid (FOL-PGA) and triphenylphosphonium (TPP-PGA) and the potential on the delivery of acetogenin-enriched Annona muricata Linn leaf extract to ovarian cancer cells. FOL-PGA and TPP-PGA were successfully synthesized and used to fabricate FOL-decorated nanoparticles (FOL-NPs) and FOL-/TPP-decorated nanoparticles (FOL/TPP-NPs) by blending two polymers at a mass ratio of 1:1. All nanoparticles had small size of around 100 nm, narrow size distribution and high negative surface charge about-30 mV. The stable FOL/TPP-NPs showed highest drug loading of 14.9 +/- 1.9% at 1:5 ratio of extract to polymer and reached to 35.8 +/- 2.1% at higher ratio. Both nanoparticles released the extract in a biphasic sustained release manner over 5 days. The toxicity of the extract to SKOV3 cells was potentiated by FOL-NPs and FOL/TPP-NPs by 2.0 - 2.6 fold through induction of cell apoptosis. FOL/TPP-NPs showed lower IC50 and higher cellular uptake as compared to FOL-NPs. FOL-NPs exhibited folate receptor-mediated endocytosis. FOL/TPP-NPs provided more advantages than FOL-NPs in terms of stability in physiological fluid, uptake efficiency and targeting ability to mitochondria and showed a promising potential PGA platform for targeted delivery of herbal cytotoxic extracts.

Automated summary

The study demonstrated the fabrication of poly(glycerol adipate) nanoparticles decorated with folic acid and triphenylphosphonium and their potential for delivering acetogenin-enriched leaf extract to ovarian cancer cells. The nanoparticles exhibited small size, narrow size distribution, high negative surface charge, and a biphasic sustained release of the extract. The FOL/TPP-decorated nanoparticles showed higher drug loading, enhanced toxicity to cancer cells, and improved cellular uptake compared to FOL-decorated nanoparticles. The FOL/TPP-NPs also demonstrated better stability, uptake efficiency, and targeting ability to mitochondria.