Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy

Abstract

Annonaceous acetogenins (ACGs) are a large family of fatty acid derived natural products that are exclusively isolated from the Annonaceae species. Many members of this diverse family have a broad spectrum of biological activities, the most impressive of which is anticancer activity. However, their poor solubility and severe toxicity restrict their clinical application, and their complicated composition hinders their formulation and drug delivery. In this study, β-cyclodextrin was modified with folic acid (FA) and then combined with soybean lecithin to prepare FA-modified ACGs nanosuspensions (FA-ACGs-NSps). The obtained FA-ACGs-NSps had a high drug payload of 57.59% and average particle size of 199.5 nm, and they exhibited sustained drug release within 142 hours. In comparison with ACGs-NSps, FA-ACGs-NSps showed significantly enhanced cytotoxicity and higher cell uptake toward folate receptor-positive 4T1 cell lines. An in vivo study demonstrated that FA-ACGs-NSps more effectively accumulated in tumors and enhanced the antitumor therapeutic efficacy with less toxicity in 4T1 tumor bearing mice. Therefore, FA-ACGs-NSps may be a promising drug delivery system for ACGs to improve their therapeutic window and may be suitable for clinical application to treat folate-positive tumors.

Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy

“…The competitive inhibition groups showed less cytotoxicity than targeting group when cells treated on the same dosage (Figure S2). Therefore, the enhanced cytotoxicity of DOX-PDA-FA (RGD)-NPs could be attributed to the fact that FA (RGD) played a key role in promoting the cellular uptake of targeting NPs into FR (αvβ 3 /αvβ 5 receptors)-positive tumor cells (Hong et al., 2017 ).…”

Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy

“…35 Histological analysis of main organs was performed by H&E staining. As shown in Figure S6, compared with the saline treatment group, no obvious difference was observed in the RGDfCSeNPs@DOX/siRNA treatment group.…”

A Valid Bisphosphonate Modified Calcium Phosphate-Based Gene Delivery System: Increased Stability and Enhanced Transfection Efficiency In Vitro and In Vivo

“…Folate receptor is overexpressed in 4T1 cells, but rarely expressed in HepG2 cells, so 4T1 cells and HepG2 cells were selected for experiment [36,37,38,39]. Herein, cytotoxicity of FA-PEG-Pam/CaP/NDs and its reference formulations was evaluated on HepG2 and 4T1 cells by the MTT assay.…”