Chitosan-g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging

Breast cancer is the leading cause of death among womenglobally.Approximately 80% of all breast cancers diagnosed are overexpressedwith estrogen receptors (ERs). In this study, we have developed anestrone (Egen)-grafted chitosan-based polymeric nanocarrier for thetargeted delivery of palbociclib (PLB) to breast cancer. The nanoparticles(NPs) were prepared by solvent evaporation using the ionic gelationmethod and characterized for particle size, zeta potential, polydispersity,surface morphology, surface chemistry, drug entrapment efficiency,cytotoxicity assay, cellular uptake, and apoptosis study. The developedPLB-CS NPs and PLB-CS-g-Egen NPs had a particle size of 116.3 & PLUSMN;1.53 nm and 141.6 & PLUSMN; 1.97 nm, respectively. The zeta potentialof PLB-CS NPs and PLB-CS-g-Egen NPs was found to be 18.70 & PLUSMN; 0.416mV and 12.45 & PLUSMN; 0.574 mV, respectively. The morphological analysisdemonstrated that all NPs were spherical in shape and had a smoothsurface. An in vitro cytotoxicity assay was performedin estrogen receptor (ER)-expressing MCF7 cells and T47D cells, whichsuggested that targeted NPs were 57.34- and 30.32-fold more cytotoxiccompared to the pure PLB, respectively. Additionally, cell cycle analysisconfirmed that cell cycle progression from the G1 into S phase wasblocked more efficiently by targeted NPs compared to nontargeted NPsand PLB in MCF7 cells. In vivo pharmacokinetic studiesdemonstrated that entrapment of the PLB in the NPs improved the half-lifeand bioavailability by & SIM;2-3-fold. Further, ultrasoundand photoacoustic imaging of DMBA induced breast cancer in the Sprague-Dawley(SD) rat showed that targeted NPs completely vanished breast tumor,reduced hypoxic tumor volume, and suppressed tumor angiogenesis moreefficiently compared to the nontargeted NPs and free PLB. Further, in vitro hemocompatibility and histopathology studies suggestedthat NPs were biocompatible and safe for clinical use.