Immunomodulatory and Antitumor Activity of Surface-Functionalized Lactoferrin Nanoparticles in Ovarian Carcinoma

Objective The study aimed fabricate Anti-Her2 carfilzomib loaded lactoferrin nanoparticles in order to address the shortcomings of carfilzomib related to poor half life, low solubility, and poor in vivo stability. The objective was to modify the programmable assembly of protein with biomarkers and imaging probe to ameliorate precise targeted theragnostics against ovarian cancer Method Carfilzomib loaded lactoferrin nanoparticles were fabricated using Desolvation technique to obtain optimal composition using Full factorial design. Further, surface functionalization with FITC tagged anti-Her2(Ab) was performed using EDC-NHS carbodiimide chemistry. Detailed characterization and in vitro evaluation including cellular uptake studies in SKOV-3 cells were performed. Results The carfilzomib loaded lactoferrin nanoparticles(CFZ-LF-NPs) were found to be uniformly distributed in range of 100-150nm. The percentage drug loading and entrapment efficiency was found to be 14.14 ± 0.521% and 86% ± 0.289, respectively. CFZ-LF-NPs showed prolong drug release till 8 days at physiological pH(7.4), while 91.932 ± 0.549% of drug release at tumor pH 5.5 on day 4, thereby indicating pH triggered drug release. NMR, and fluorescent microscopy confirms successful conjugation of anti-Her2(Ab) with CFZ-LF-NPs. ELISA test for anti-HER2 conjugated NPs(FITC-AntiHer2-CFZ-LF-NPs) revealed the highest percent of antibody(> 60 ± 0.225%) conjugation with nanoparticles above the concentration of 5 ug/ml.The MTT assay, cellular uptake assay and tumor growth inhibition studies in treated mice unravels high cytotoxicity in nanoconjugates(FITC-AntiHer2-CFZ-LF-NPs) as compared to non-conjugated NPs and plain drug. Conclusion The potential approach may emerge in future as a molecular-docks comprising a immunotherapy-based theragnostic in cancer.