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1.
J Med Chem ; 66(13): 8687-8704, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37387570

RESUMO

In this article, we report IriPlatins 1-3, a new class of heterobimetallic Ir(III)-Pt(IV) conjugates as multifunctional potent anticancer theranostic agents. In the designed construction, the octahedral Pt(IV) prodrug is tethered to the cancer cell targeting biotin ligand through one of the axial sites and the other axial site of Pt(IV) center is attached to multifunctional Ir(III) complexes that possess organelle-targeting capabilities with excellent anticancer and imaging properties. The conjugates preferentially accumulate within the mitochondria of cancer cells, and subsequently, Pt(IV) is reduced to Pt(II) species that concomitantly releases both the Ir(III) complex and biotin from its axial sites. The IriPlatin conjugates demonstrate potent anticancer activity in various 2D monolayer cancer cells, including the cisplatin-resistant cells in the nanomolar concentrations and 3D multicellular tumor spheroids. The mechanistic investigation of conjugates suggests that the loss of MMP, generation of ROS, and caspase-3-mediated apoptosis are responsible for cell death.


Assuntos
Antineoplásicos , Pró-Fármacos , Platina , Irídio/farmacologia , Medicina de Precisão , Biotina , Antineoplásicos/farmacologia , Pró-Fármacos/farmacologia , Linhagem Celular Tumoral
2.
Int J Biol Macromol ; 164: 4252-4262, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910962

RESUMO

Tissue engineering aims at replacement, repair, and regeneration of tissues by a combination of scaffolds, growth factors, and cells. In this study, we report the synthesis of biodegradable composite scaffolds fortified with mesoporous zinc silicate (mZS) and assessment of in vitro properties for bone tissue engineering (BTE) applications. The scaffolds consisted of chitosan (CS) incorporated with mZS at 0.1, 0.2, 0.3, and 0.5 wt%. The bio-composite scaffolds were visualized using Field Emission Scanning Electron Microscopy (FE-SEM). The incorporation of mZS was confirmed using Energy dispersive x-ray (EDS) analysis. Biomineralization studies were conducted in simulated body fluid (SBF) and indicated bioactivity of fabricated scaffolds. The scaffolds also displayed antibacterial action against Staphylococcus aureus. Cellular attachment within the scaffold network established biocompatibility of the material. Incorporation of mZS within the chitosan scaffolds matrix improved properties such as porosity, degradation rate, and biomineralization. Therefore, fabricated scaffolds exhibit exceptional features and have the potential to serve as an implant for BTE applications.


Assuntos
Materiais Biocompatíveis/química , Osso e Ossos , Quitosana/química , Silicatos/química , Engenharia Tecidual , Compostos de Zinco/química , Antibacterianos/química , Antibacterianos/farmacologia , Regeneração Óssea , Testes de Sensibilidade Microbiana , Porosidade , Staphylococcus aureus/efeitos dos fármacos , Alicerces Teciduais
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