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The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity
- Source :
- Journal of controlled release 275 (2018): 177–185. doi:10.1016/j.jconrel.2018.02.025, info:cnr-pdr/source/autori:Falvo E.; Malagrino F.; Arcovito A.; Fazi F.; Colotti G.; Tremante E.; Di Micco P.; Braca A.; Opri R.; Giuffre A.; Fracasso G.; Ceci P./titolo:The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity/doi:10.1016%2Fj.jconrel.2018.02.025/rivista:Journal of controlled release/anno:2018/pagina_da:177/pagina_a:185/intervallo_pagine:177–185/volume:275
- Publication Year :
- 2018
- Publisher :
- Elsevier, Amsterdam , Paesi Bassi, 2018.
-
Abstract
- A genetically engineered human ferritin heavy chain (HFt)-based construct has been recently shown by our group to efficiently entrap and deliver doxorubicin to cancer cells. This construct, named HFt-MP-PAS, contained a tumor-selective sequence (MP) responsive to proteolytic cleavage by tumor proteases (MMPs), located between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). HFt-MP-PAS displayed excellent therapeutic efficacy in xenogenic pancreatic and head and neck cancer models in vivo, leading to a significant increase in overall animal survivals. Here we report a new construct obtained by the genetic insertion of two glutamate residues in the PAS sequence of HFt-MP-PAS. Such new construct, named HFt-MP-PASE, is characterized by improved performances as drug biodistribution in a xenogenic pancreatic cancer model in vivo. Moreover, HFt-MP-PASE efficiently encapsulates the anti-cancer drug mitoxantrone (MIT), and the resulting MIT-loaded nanoparticles proved to be more soluble and monodispersed than the HFt-MP-PAS counterparts. Importantly, in vitro MIT-loaded HFt-MP-PASE kills several cancer cell lines of different origin (colon, breast, sarcoma and pancreas) at least as efficiently as the free drug. Finally, our MIT loaded protein nanocages allowed in vivo an impressive incrementing of the drug accumulation in the tumor with respect to the free drug.
- Subjects :
- 0301 basic medicine
Biodistribution
Proteases
Glutamic Acid
Pharmaceutical Science
Antineoplastic Agents
02 engineering and technology
Serine
03 medical and health sciences
Doxorubicin (PubChem CID:31703)
In vivo
Cell Line, Tumor
Protein-cage nanocarrier
Pasylated ferritin
Humans
Tissue Distribution
cancer
drug-delivery
drug-encapsulation
mitoxantrone
pasylated ferritin
protein-cage nanocarrier
3003
Settore BIO/10 - BIOCHIMICA
Peptide sequence
Cancer
Drug Carriers
Chemistry
Mitoxantrone (PubChem CID:4212)
Drug-delivery
Drug-encapsulation
Mitoxantrone
021001 nanoscience & nanotechnology
In vitro
030104 developmental biology
Biochemistry
Doxorubicin
Apoferritins
Cancer cell
Drug delivery
Nanoparticles
0210 nano-technology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of controlled release 275 (2018): 177–185. doi:10.1016/j.jconrel.2018.02.025, info:cnr-pdr/source/autori:Falvo E.; Malagrino F.; Arcovito A.; Fazi F.; Colotti G.; Tremante E.; Di Micco P.; Braca A.; Opri R.; Giuffre A.; Fracasso G.; Ceci P./titolo:The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity/doi:10.1016%2Fj.jconrel.2018.02.025/rivista:Journal of controlled release/anno:2018/pagina_da:177/pagina_a:185/intervallo_pagine:177–185/volume:275
- Accession number :
- edsair.doi.dedup.....0c0c87ae68646e9ef809a087b3fe1f4a
- Full Text :
- https://doi.org/10.1016/j.jconrel.2018.02.025