ABSTRACT
Despite recent medical progress, cervical cancer remains a major global health concern for women. Current standard treatments have limitations such as non-specific toxicity that necessitate development of safer and more effective therapeutic strategies. This research evaluated the combinatorial effects of olive leaf extract (OLE), rich in anti-cancer polyphenols, and the oncolytic Newcastle disease virus (NDV) against human cervical cancer cells. OLE was efficiently encapsulated (>94% loading) within MF59 lipid nanoparticles and nanostructured lipid carriers (NLCs; contains Precirol as NLC-P, contains Lecithin as NLC-L) to enhance stability, bioavailability, and targeted delivery. Physicochemical analysis confirmed successful encapsulation of OLE within nanoparticles smaller than 150 nm. In vitro cytotoxicity assays demonstrated significantly higher toxicity of the OLE-loaded nanoparticle formulations on HeLa cancer cells versus HDF normal cells (P<0.05). MF59 achieved the highest encapsulation efficiency, while NLC-P had the best drug release profile. NDV selectively infected and killed HeLa cells versus HDF cells. Notably, combining NDV with OLE-loaded nanoparticles led to significantly enhanced synergistic cytotoxicity against cancer cells (P<0.05), with NLC-P (OLE) and NDV producing the strongest effects. Apoptosis and cell cycle analyses confirmed the increased anti-cancer activity of the combinatorial treatment, which induced cell cycle arrest. This study provides evidence that co-delivery of OLE-loaded lipid nanoparticles and NDV potentiates anti-cancer activity against cervical cancer cells in vitro through a synergistic mechanism, warranting further development as a promising alternative cervical cancer therapy.
Subject(s)
Nanoparticles , Newcastle disease virus , Olea , Plant Extracts , Plant Leaves , Uterine Cervical Neoplasms , Humans , Female , Plant Extracts/pharmacology , Plant Extracts/chemistry , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/pathology , HeLa Cells , Newcastle disease virus/drug effects , Plant Leaves/chemistry , Nanoparticles/chemistry , Olea/chemistry , Drug Carriers/chemistry , Lipids/chemistry , Drug Synergism , Apoptosis/drug effects , LiposomesABSTRACT
Breast cancer resistance to chemotherapy necessitates novel combination therapeutic approaches. Linc-RoR is a long intergenic noncoding RNA that regulates stem cell differentiation and promotes metastasis and invasion in breast cancer. Herein, we report a dual delivery system employing polyamidoamine dendrimers to co-administer the natural compound curcumin and linc-RoR siRNA for breast cancer treatment. Polyamidoamine dendrimers efficiently encapsulated curcumin and formed complexes with linc-RoR siRNA at an optimal N/P ratio. In MCF-7 breast cancer cells, the dendriplexes were effectively internalized and the combination treatment synergistically enhanced cytotoxicity, arresting the cell cycle at the G1 phase and inducing apoptosis. Linc-RoR gene expression was also significantly downregulated. Individual treatments showed lower efficacy, indicating synergism between components. Mechanistic studies are warranted to define the molecular underpinnings of this synergistic interaction. Our findings suggest dual delivery of linc-RoR siRNA and curcumin via dendrimers merits further exploration as a personalized therapeutic approach for overcoming breast cancer resistance.