Hyaluronic acid driven biomimetic nanoparticles loaded CDK4/6 inhibitor for effective targeted breast cancer therapy.

Nanoparticulate drug delivery systems suffer from several drawbacks, such as decreased site-specific delivery, immune recognition, and diminished therapeutic efficacy. Here, we fabricated Hyaluronic acid anchored erythrocyte membrane camouflaged nanocarrier loaded with Palbociclib (HA-RBC-PAL-LPHYNPs) to facilitate targeted breast cancer therapy via CD44 receptors. The HA-RBC-PAL-LPHYNPs were evaluated for its particle size, PDI and %EE and drug release profile, exhibiting exceptional physicochemical property and sustained release. It exhibited remarkable cytotoxicity, apoptosis, ROS production, MMP depolarisation, diminished wound healing and colony formation in cell line studies. Due to its camouflaged surface, it depicted favourable colloidal stability, hemocompatibility and immune escape ability. HA-RBC-PAL-LPHYNPs displayed a 1.73-fold reduction in the 3D mammosphere diameter than free PAL. In western blot study, an intensified BAX/Bcl2 ratio was seen, corroborating apoptosis. The cell cycle study depicted and extensive G0/G1 phase arrest. Annexin V-FITC&PI assay showed an apoptotic pathway for MCF-7, whereas a necrotic pathway for MDA-MB-231 cells. In vivo Pharmacokinetic study depicted a 2.26 and 2-fold enhancement in AUC and MRT, with HA-RBC-PAL-LPHYNPs than free PAL. Furthermore, a 5.33-fold enhanced in vivo blood distribution was seen with HA-RBC-FITC-LPHYNPs compared to free FITC, validating its long-circulating nature. The results of an acute toxicity study validated its exceptional safety profile.