<p>Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells</p>

Abstract

Background: Psoralen (PSO), a major active component of Psoralea corylifolia, has been shown to overcome multidrug resistance in cancer. A drug carrier comprising a lipid-monolayer shell and a biodegradable polymer core for sustained delivery and improved efficacy of drug have exhibited great potential in efficient treatment of cancers. Methods: The PSO-loaded lipid polymer hybrid nanoparticles were prepared and characterized. In vitro cytotoxicity assay, cellular uptake, cell cycle analysis, detection of ROS level and mitochondrial membrane potential (ΔΨm) and western blot were performed. Results: The P-LPNs enhanced the cytotoxicity of doxorubicin (DOX) 17-fold compared to free DOX in multidrug resistant HepG2/ADR cells. Moreover, P-LPNs displayed pro-apoptotic activity, increased levels of ROS and depolarization of ΔΨm. In addition, there were no significant effects on cellular uptake of DOX, cell cycle arrest, or the expression of P-glycoprotein. Mechanistic studies suggested that P-LPNs enhanced DOX cytotoxicity by increased release of cytochrome c and enhanced caspase3 cleavage, causing apoptosis in HepG2/ADR cells. Conclusion: The lipid-polymer hybrid nanoparticles can be considered a powerful and promising drug delivery system for effective cancer chemotherapy.

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound—An In Vitro Study

“…In addition, the combination of ACAT-Se-PLGA-77KL-NPs and DOX was the only condition able to sensitize the resistant MDR tumor cells, achieving 76.7% of cytotoxicity as detected by the MTT assay. The synergistic effect of the combined therapy with the NPs and DOX in the resistant cell line can be also associated to the Pluronic ® F-127 ability to inhibit P-gp efflux pumps, since over expression of P-gp is one of the resistance mechanisms in MDR cells [75,76]. These results suggest that the association of the proposed pHresponsive nanocarrier with DOX is a promising approach to improve antitumor therapy and overcome MDR.…”

Five Constituents Contributed to the Psoraleae Fructus-Induced Hepatotoxicity via Mitochondrial Dysfunction and Apoptosis

“…Compared with the control, bavachin, bavachinin, neobavaisoflavone, and bakuchiol had markedly and progressively increased the cell early apoptosis percentage as the concentration increased. Based on these data and established pharmacological research ( Li F. et al, 2017 ; Huang et al, 2019 ; Yuan et al, 2019 ), we supposed that monoterpenes and flavonoids could be toxic constituents, whereas coumarins would be active ingredients. Thus, the over-enrichment of these two types of components should be avoided in clinical applications to ensure medication safety.…”

Multifunctional PLGA nanoparticles combining transferrin-targetability and pH-stimuli sensitivity enhanced doxorubicin intracellular delivery and in vitro antineoplastic activity in MDR tumor cells

“…MCF-7 and NCI/ADR-RES cells were seeded in 60 mm petri dishes at 1.5x105 cells/mL and allowed to grow for 24 h. Free DOX, DOX-PLGA-NPs and Tf-DOX-PLGA-NPs were applied at concentrations of 2 µg/mL to MCF-7 and 10 µg/mL to NCI/ADR-RES cells for 24 h. Then, the cells were washed, harvested and incubated with 0.5 mL of medium containing 5 µM of the ROS-sensitive probe 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) for 20 minutes in the dark and then analyzed by the BD AccuriC6 flow cytometer (BD Bioscience) [31]. The non-treated cells were taken as negative control.…”