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1.
Int J Biol Macromol ; 272(Pt 2): 132940, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38848845

ABSTRACT

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.


Subject(s)
Chitosan , Fingolimod Hydrochloride , Nanoparticles , Chitosan/chemistry , Chitosan/analogs & derivatives , Nanoparticles/chemistry , Humans , Animals , Cell Line, Tumor , Fingolimod Hydrochloride/pharmacology , Fingolimod Hydrochloride/chemistry , Fingolimod Hydrochloride/administration & dosage , Mice , Female , Drug Carriers/chemistry , Apoptosis/drug effects , Polyethylene Glycols/chemistry , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology
2.
Biomed Pharmacother ; 177: 116951, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38901207

ABSTRACT

The emerging strategy of biomimetic nanoparticles (NPs) via cellular membrane camouflage holds great promise in cancer therapy. This scholarly review explores the utilization of cellular membranes derived from diverse cellular entities; blood cells, immune cells, cancer cells, stem cells, and bacterial cells as examples of NP coatings. The camouflaging strategy endows NPs with nuanced tumor-targeting abilities such as self-recognition, homotypic targeting, and long-lasting circulation, thus also improving tumor therapy efficacy overall. The comprehensive examination encompasses a variety of cell membrane camouflaged NPs (CMCNPs), elucidating their underlying targeted therapy mechanisms and delineating diverse strategies for anti-cancer applications. Furthermore, the review systematically presents the synthesis of source materials and methodologies employed in order to construct and characterize these CMCNPs, with a specific emphasis on their use in cancer treatment.

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