Novel GnRH analogue decorated paclitaxel and CQDs co-loaded theranostic zein nanoparticles for treatment of breast cancer: Formulation optimization, in vitro and in vivo evaluation.

Breast cancer is a diverse disease with intertumoral as well as intratumoral heterogeneity, which results in different treatment regimens, disease prognosis, and treatment outcomes. This heterogeneity generally arises due to genetic and epigenetic changes. This requires a delivery system that can treat the tumor as well as provide real-time monitoring of the tumor, i.e., size and location. Hence, current research work is focused on the development of biodegradable and cost-effective ligand-decorated theranostic zein nanoparticles (NPs) prepared by co-loading of an imaging agent, i.e., carbon quantum dots (CQDs), and an anticancer drug, paclitaxel (PCT), simultaneously, whereas leuprorelin acetate (LA) was used as a ligand and electrostatically coated on the surface of zein NPs. CQDs and PCT loading inside zein NPs were optimized using a Box-Behnken design. The optimized batch of CQDs and PCT-loaded zein NPs showed a particle size of 154.23 ± 7.51 nm and +19.65 ± 0.26 mV zeta potential, whereas the % entrapment efficiency of PCT and CQDs was found to be >90%. The LA-coated zein NPs showed a better cytotoxicity profile compared to the pure drug and uncoated zein NPs in MCF-7 and MDA-MB-231 cells. The qualitative and quantitative cellular uptake studies showed remarkably higher uptake of LA-coated zein NPs. An in vivo animal study showed that LA-coating acted as a protein corona, which significantly improved the mean blood circulation time and showed a better tumor regression profile than Nab PCT. Overall, ligand-decorated theranostic zein NPs showed a comparatively better pharmacokinetic profile, lower toxicity, and higher efficacy than the marketed nab PCT formulation.