Development of PEG-biotin mixed micelles for myricetin delivery and their anti-colorectal cancer efficacy

Myricetin (MYR) demonstrates anti-colorectal cancer potential; nonetheless, its poor solubility and limited in vivo exposure hinder further development. In this study, a biotin-decorated mixed micelle delivery system (MYR@Bi-PEG-PVP) was constructed using Bi-PEG and PVP-K30, with a non-targeted micelle (MYR@PEG-PVP) as control. The optimal MYR@Bi-PEG-PVP formed well-dispersed spherical nanoparticles with a mean nano-sized particles (154.38 ± 1.55 nm), high encapsulation efficiency (87.99 ± 0.20%), and drug loading (12.18 ± 0.09%), which indicates that biotin modification did not compromise the loading capacity. In vitro release (in pH 6.8 medium) showed sustained release for both micellar formulations with markedly higher cumulative release than free MYR. Cyanine 2 (Cy2)-labeled uptake experiments demonstrated enhanced cellular internalization of the biotinylated micelles in HCT116 cells. Consistently, MYR@Bi-PEG-PVP exhibited stronger growth inhibition and anti-invasion activity than free MYR and non-targeted micelles. Pharmacokinetic evaluation in Sprague-Dawley rats (10 mg/kg, i.v.) further confirmed improved systemic exposure, with prolonged half-life (3.87 ± 0.14 h), increased AUC 0−24 (27.23 ± 1.51 µg·h/mL) and C max (9.25 ± 0.36 µg/mL) compared with free MYR. Patient-derived colorectal cancer organoids were successfully established and used to validate therapeutic efficacy. MYR@Bi-PEG-PVP produced more pronounced organoid growth suppression and regulated apoptosis-related proteins by upregulating Bax and downregulating Bcl-2. Overall, MYR@Bi-PEG-PVP provides a feasible targeted nanoplatform to enhance MYR delivery and anti-colorectal cancer activity in both cell and organoid models.