Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model

Abstract

Pancreatic cancer (PC) represents an intriguing topic for researchers. To date, the prognosis of metastasized PC is poor with just 7% of patients exceeding a five-year survival period. Thus, molecular modifications of existing drugs should be developed to change the course of the disease. Our previously generated nanocages of Mitoxantrone (MIT) encapsulated in human H-chain Ferritin (HFt), designated as HFt-MP-PASE-MIT, has shown excellent tumor distribution and extended serum half-life meriting further investigation for PC treatment. Thus, in this study, we used the same nano-formulation to test its cytotoxicity using both in vitro and in vivo assays. Interestingly, both encapsulated and free-MIT drugs demonstrated similar killing capabilities on PaCa44 cell line. Conversely, in vivo assessment in a subcutaneous PaCa44 tumor model of PC demonstrated a remarkable capability for encapsulated MIT to control tumor growth and improve mouse survival with a median survival rate of 65 vs. 33 days for loaded and free-MIT, respectively. Interestingly, throughout the course of mice treatment, MIT encapsulation did not present any adverse side effects as confirmed by histological analysis of various murine tissue organs and body mass weights. Our results are promising and pave the way to effective PC targeted chemotherapy using our HFt nanodelivery platforms.

Mitoxantrone and Mitoxantrone-Loaded Iron Oxide Nanoparticles Induce Cell Death in Human Pancreatic Ductal Adenocarcinoma Cell Spheroids

“…For instance, the effects of SPIONs coated with curcumin and multifunctionalized magnetic iron oxide nanoparticles containing an anti-CD47 antibody, as well as the chemotherapeutic agent, gemcitabine, have been the subjects of former research [ 20 , 21 ]. However, MTO, a cytostatic drug used for cancer therapy and multiple sclerosis treatment with a potency up to 20,000 times higher than that of gemcitabine, has shown promising preclinical results for the treatment of pancreatic cancer [ 22 , 23 , 24 , 25 ]. Nevertheless, MTO did not show a significant response rate in a phase II clinical study including patients with advanced pancreatic carcinoma, as one of the main therapeutic limitations were dose-dependent hematologic side effects [ 26 ].…”

Widespread in vivo efficacy of The-0504: A conditionally-activatable nanoferritin for tumor-agnostic targeting of CD71-expressing cancers

“…In recent years, we have demonstrated that the ability of the human H-type ferritin (HFt) to bind to and being internalized through the transferrin receptor 1 (CD71 or TfR1) could be exploited to load different chemotherapeutic drugs into the ferritin cavity and deliver them to the cancer cells that often overexpress CD71 [ [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] ] [ [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] ] [ [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] ]. Herein, we propose a first-in-class nanoparticle named The-0504 that incorporates in a single formulation many advantages of each of the above classes of cancer therapeutics, and at the same time has been carefully designed to minimize hurdles.…”