Self-activating chitosan-based nanoparticles for sphingosin-1 phosphate modulator delivery and selective tumor therapy.

Autor: Mahmudi H; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Shahpouri M; Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Adili-Aghdam MA; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Akbari M; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Salemi A; Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Alimohammadvand S; Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Barzegari A; Innovation Center for Stem Cell Research and Regenerative Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Mazloomi M; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Jaymand M; Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: m.jaymand@gmail.com., Jahanban-Esfahlan R; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: jahanbanr@tbzmed.ac.ir.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Jun; Vol. 272 (Pt 2), pp. 132940. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1016/j.ijbiomac.2024.132940
Abstrakt: This study reports on the design and synthesis of hypoxia responsive nanoparticles (HRNPs) composed of methoxy polyethylene glycol-4,4 dicarboxylic azolinker-chitosan (mPEG-Azo-chitosan) as ideal drug delivery platform for Fingolimod (FTY720, F) delivery to achieve selective and highly enhanced TNBC therapy in vivo. Herein, HRNPs with an average size of 49.86 nm and a zeta potential of +3.22 mV were synthetized, which after PEG shedding can shift into a more positively-charged NPs (+30.3 mV), possessing self-activation ability under hypoxia situation in vitro, 2D and 3D culture. Treatment with lower doses of HRNPs@F significantly reduced MDA-MB-231 microtumor size to 15 %, induced apoptosis by 88 % within 72 h and reduced highly-proliferative 4 T1 tumor weight by 87.66 % vs. ∼30 % for Fingolimod compared to the untreated controls. To the best of our knowledge, this is the first record for development of hypoxia-responsive chitosan-based NPs with desirable physicochemical properties, and selective self-activation potential to generate highly-charged nanosized tumor-penetrating chitosan NPs. This formulation is capable of localized delivery of Fingolimod to the tumor core, minimizing its side effects while boosting its anti-tumor potential for eradication of TNBC solid tumors.
Competing Interests: Declaration of competing interest None to declare.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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