Photoactivation of Diiodido-Pt(IV) Complexes Coupled to Upconverting Nanoparticles
| العنوان: | Photoactivation of Diiodido-Pt(IV) Complexes Coupled to Upconverting Nanoparticles |
|---|---|
| المؤلفون: | Marta Maria Natile, Giovanni Natile, Stefanie Perfahl, Patrick J. Bednarski, Carola Schulzke, Christiane A. Helm, Heba S. Mohamad |
| المصدر: | Molecular pharmaceutics 13 (2016): 2346–2362. doi:10.1021/acs.molpharmaceut.6b00108 info:cnr-pdr/source/autori:Perfahl S.; Natile M.M.; Mohamad H.S.; Helm C.A.; Schulzke C.; Natile G.; Bednarski P.J./titolo:Photoactivation of Diiodido-Pt(IV) Complexes Coupled to Upconverting Nanoparticles/doi:10.1021%2Facs.molpharmaceut.6b00108/rivista:Molecular pharmaceutics (Print)/anno:2016/pagina_da:2346/pagina_a:2362/intervallo_pagine:2346–2362/volume:13 |
| بيانات النشر: | American Chemical Society, Washington, DC , Stati Uniti d'America, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Organoplatinum Compounds, Photochemistry, Pharmaceutical Science, Antineoplastic Agents, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, chemistry.chemical_compound, Microscopy, Electron, Transmission, X-Ray Diffraction, Cell Line, Tumor, Drug Discovery, Humans, Peptide bond, Prodrugs, Upconverting nanoparticles, Carboxylate, photoactivated chemotherapy, Cytotoxicity, Chemistry, DNA, Prodrug, 021001 nanoscience & nanotechnology, 0104 chemical sciences, upconverting nanoparticles, Nanocrystal, Covalent bond, photoactivatable Pt complexes, anticancer prodrug, Nanoparticles, Molecular Medicine, Surface modification, 0210 nano-technology |
| الوصف: | The preparation, characterization, and surface modification of upconverting lanthanide-doped hexagonal NaGdF4 nanocrystals attached to light sensitive diiodido Pt(IV) complexes is presented. The evaluation for photo activation and cytotoxicity of the novel carboxylated diiodido Pt(IV) cytotoxic prodrugs by near-infrared (NIR) light (2 = 980 nm) is also reported. We attempted two different strategies for attachment of light-sensitive diiodido Pt(IV) complexes to Yb,Er- and Yb,Tm-doped beta-NaGdF4 upconverting nanoparticles (UCNPs) in order to provide nanohybrids, which offer unique opportunities for selective drug activation within the tumor cells and subsequent spatiotemporal controlled drug release by NIR-to-visible light-upconversion: (A) covalent attachment of the Pt(IV) complex via amide bond formation and (B) carboxylate exchange of oleate on the surface of the UCNPs with diiodido Pt(IV) carboxylato complexes. Initial feasibility studies showed that NIR applied by a 980 nm laser had only a slight effect on the stability of the various diiodido Pt(IV) complexes, but when UCNPs were present more rapid loss of the ligand metal charge transfer (LMCT) bands of the diiodido Pt(IV) complexes was observed. Furthermore, Pt released from the Pt(IV) complexes platinated calf-thymus DNA (ct-DNA) more rapidly when NIR was applied compared to dark controls. Of the two attachment strategies, method A with the covalently attached diiodido Pt(IV) carboxylates via amide bond formation proved to be the most effective method for generating UCNPs that release Pt when irradiated with NIR; the released Pt was also able to bind irreversibly to calf thymus DNA. Nonetheless, only ca. 20% of the Pt on the surface of the UCNPs was in the Pt(IV) oxidation state, the rest was Pt(II), indicating chemical reduction of the diiodido Pt(IV) prodrug by the UCNPs. Cytotoxicity studies with the various UCNP Pt conjugates and constructs, tested on human leukemia HL60 cells in culture, indicated a substantial increase in cytotoxicity when modified UCNPs were combined with five rounds of 30 min irradiation with NIR compared to dark controls, but NIR alone also had a significant cytotoxic effect at this duration. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0dfdb5872166e37c8e8fee73ef76127cTest https://publications.cnr.it/doc/359889Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....0dfdb5872166e37c8e8fee73ef76127c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |