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

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 previo...

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Autores principales:	Giamaica Conti, Martina Pitea, Riccardo Ossanna, Roberta Opri, Giada Tisci, Elisabetta Falvo, Giulio Innamorati, Esther Ghanem, Andrea Sbarbati, Pierpaolo Ceci, Giulio Fracasso
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	targeted therapy pancreatic cancer human ferritin transferrin receptor (CD71) mitoxantrone Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/39a8cae188c14ca3b763e71c4222e23c
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spelling	oai:doaj.org-article:39a8cae188c14ca3b763e71c4222e23c2021-11-25T16:49:42ZMitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model10.3390/biomedicines91116222227-9059https://doaj.org/article/39a8cae188c14ca3b763e71c4222e23c2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1622https://doaj.org/toc/2227-9059Pancreatic 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.Giamaica ContiMartina PiteaRiccardo OssannaRoberta OpriGiada TisciElisabetta FalvoGiulio InnamoratiEsther GhanemAndrea SbarbatiPierpaolo CeciGiulio FracassoMDPI AGarticletargeted therapypancreatic cancerhuman ferritintransferrin receptor (CD71)mitoxantroneBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1622, p 1622 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	targeted therapy pancreatic cancer human ferritin transferrin receptor (CD71) mitoxantrone Biology (General) QH301-705.5
spellingShingle	targeted therapy pancreatic cancer human ferritin transferrin receptor (CD71) mitoxantrone Biology (General) QH301-705.5 Giamaica Conti Martina Pitea Riccardo Ossanna Roberta Opri Giada Tisci Elisabetta Falvo Giulio Innamorati Esther Ghanem Andrea Sbarbati Pierpaolo Ceci Giulio Fracasso Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model
description	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.
format	article
author	Giamaica Conti Martina Pitea Riccardo Ossanna Roberta Opri Giada Tisci Elisabetta Falvo Giulio Innamorati Esther Ghanem Andrea Sbarbati Pierpaolo Ceci Giulio Fracasso
author_facet	Giamaica Conti Martina Pitea Riccardo Ossanna Roberta Opri Giada Tisci Elisabetta Falvo Giulio Innamorati Esther Ghanem Andrea Sbarbati Pierpaolo Ceci Giulio Fracasso
author_sort	Giamaica Conti
title	Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model
title_short	Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model
title_full	Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model
title_fullStr	Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model
title_full_unstemmed	Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model
title_sort	mitoxantrone-loaded nanoferritin slows tumor growth and improves the overall survival rate in a subcutaneous pancreatic cancer mouse model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/39a8cae188c14ca3b763e71c4222e23c
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Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model

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