Reduction- and pH-Sensitive Hyaluronan Nanoparticles for Delivery of Iridium(III) Anticancer Drugs.
Biomacromolecules
; 18(7): 2102-2117, 2017 Jul 10.
Article
em En
| MEDLINE
| ID: mdl-28605176
ABSTRACT
The organoiridium(III) complex (Ir(III)) [(η5-Cpxbiph)Ir(phpy) (py)]PF6 containing π-bonded biphenyltetramethylcyclopentadienyl(Cpxbiph), Câ§N-chelated phenylpyridine(phpy), and pyridine (py) ligands has more potent antitumor activity as a new generation of drug than cisplatin toward various cancer cells. However, poor site-specific delivery, low solubility, and poor tumor penetration are common limitations of chemotherapy drugs. To develop CD44-targetable, pH-, and reduction-responsive drug delivery systems for Ir(III) drugs, the amphiphilic hyaluronan (HA)-based conjugates of HA-cystamin-pyrenyl (HA-ss-Py) containing disulfide bonds and HA-pyrenyl (HA-Py) were designed. The Ir(III) drug was readily loaded into these two amphiphilic conjugates and nanoparticles were formed. Dynamic light scattering (DLS) studies showed that the micelles formed from HA-ss-Py were sufficiently stable under physiological conditions, but were prone to rapid dissociation in reducing environments (20 mM glutathione (GSH)). In subsequent confocal microscopy analyses, A549 cancer cells efficiently internalized HA-based micelles. Moreover, in vitro cytotoxicity assays in A549 cells demonstrat that Ir-loaded HA-based nanoparticles have higher cytotoxicity than the free Ir(III) anticancer drug. Finally, systemic administration of Ir(III)-loaded HA-ss-Py nanoparticles enhanced tumor inhibition in vivo, and the corresponding biodistribution experiments showed that HA-ss-Py micelles accumulate in tumors. Overall, our results suggest that HA-ss-Py micelles have a great potential to be used as an effective Ir(III) drug carrier for targeted cancer therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Ácido Hialurônico
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Irídio
/
Neoplasias
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biomacromolecules
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China