Abstract: Conventional chemotherapeutic agents often suffer from limited tumor selectivity and considerable systemic toxicity, prompting a shift toward nanotechnology-based delivery approaches. Among natural compounds, flavonoids are a broad group of plant-derived polyphenols that display notable anticancer, antioxidant, and anti-inflammatory actions. However, their poor solubility, chemical instability, and rapid metabolic clearance severely restrict their clinical value. Progress in nanocarrier design has recently improved both the pharmacokinetic and pharmacodynamic behavior of flavonoids, allowing more precise delivery and controlled release. Flavonoids often encounter challenges that limit their therapeutic effectiveness. Nanocarrier-based delivery systems offer an effective way to improve the therapeutic potential of flavonoids. They enhance circulation, enable targeted delivery to tumors, and help reduce harm to healthy cells. When used in combination therapies, they can also lower side effects and improve overall treatment outcomes. This review explores emerging developments in flavonoid-loaded nanoparticles, encompassing polymeric, liposomal, micellar, metallic, and hybrid formulations applied to diverse cancers, including lung, breast, cervical, colon, and skin malignancies. Experimental data demonstrate that nanoformulation can increase bioavailability three- to eightfold, maintain drug release for roughly 48-72 hours, and lower IC₅₀ values by 30-70% compared with unformulated compounds. Mechanistically, these nanocarriers influence key oncogenic pathways-PI3K/AKT, ERK1/2, VEGF, and MMP-9 to trigger apoptosis, suppress angiogenesis, and limit metastasis. Among the examined formulations, quercetin-, apigenin- , and genistein-based nanoparticles achieved the strongest tumor-growth inhibition, reducing tumor volume by up to 80% in preclinical evaluations. Collectively, the evidence indicates that thoughtful nanocarrier engineering transforms naturally bioactive yet pharmacokinetically weak flavonoids into biocompatible, multitargeted anticancer therapeutics. Continued investigation focused on clinical translation, pharmacokinetic optimization, and co-delivery strategies will be vital for moving flavonoid nanotherapeutics from laboratory research toward practical cancer treatment
Sasmal et al. (Wed,) studied this question.