Targeted Fisetin-Encapsulated β-Cyclodextrin Nanosponges for Breast Cancer

Abstract

Fisetin (FS) is considered a safer phytomedicine alternative to conventional chemotherapeutics for breast cancer treatment. Despite its surpassing therapeutic potential, its clinical utility is hampered by its low systemic bioavailability. Accordingly, as far as we are aware, this is the first study to develop lactoferrin-coated FS-loaded β-cyclodextrin nanosponges (LF-FS-NS) for targeted FS delivery to breast cancer. NS formation through cross-linking of β-cyclodextrin by diphenyl carbonate was confirmed by FTIR and XRD. The selected LF-FS-NS showed good colloidal properties (size 52.7 ± 7.2 nm, PDI < 0.3, and ζ-potential 24 mV), high loading efficiency (96 ± 0.3%), and sustained drug release of 26 % after 24 h. Morphological examination using SEM revealed the mesoporous spherical structure of the prepared nanosponges with a pore diameter of ~30 nm, which was further confirmed by surface area measurement. Additionally, LF-FS-NS enhanced FS oral and IP bioavailability (2.5- and 3.2-fold, respectively) compared to FS suspension in rats. Antitumor efficacy evaluation in vitro on MDA-MB-231 cells and in vivo on an Ehrlich ascites mouse model demonstrated significantly higher activity and targetability of LF-FS-NS (30 mg/kg) compared to the free drug and uncoated formulation. Consequently, LF-FS-NS could be addressed as a promising formulation for the effective management of breast cancer.

Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis

“…Moreover, loading FS into NS (nanosponges) resulted in a significant decrease in Bcl-2 levels along with increased expression of the Bax gene compared to FIS alone. All therapies significantly increased the expression of the caspase-3 gene, confirming the involvement of the apoptotic process in the anti-tumor activity of FIS [167]. To determine the effectiveness of the in vivo combination therapy of FIS and gemcitabine, researchers utilized mice with an orthotopic pancreatic cancer allografts.…”

The development of nanocarriers for natural products

“…In vitro studies conducted by Aboushanab et al confirmed that LF-FS-NS increased cytotoxicity toward breast cancer cells without impacting normal cells. Moreover, in a breast cancer mouse model, LF-FS-NS exhibited higher bioavailability and targeting and significantly inhibited tumor growth by inducing apoptosis (Aboushanab et al, 2023). This innovative NDDS offers several benefits, notably high FST loading and entrapment efficiency, extended release, and augmented anticancer efficacy of FST through both passive targeting via enhanced permeability and retention effect and active targeting via LF coating.…”