Targeted iron nanoparticles with platinum-(IV) prodrugs and anti-EZH2 siRNA show great synergy in combating drug resistance in vitro and in vivo.

Title Targeted iron nanoparticles with platinum-(IV) prodrugs and anti-EZH2 siRNA show great synergy in combating drug resistance in vitro and in vivo.
Authors C. Yu; B. Ding; X. Zhang; X. Deng; K. Deng; Z. Cheng; B. Xing; D. Jin; P.'an Ma; J. Lin
Journal Biomaterials
DOI 10.1016/j.biomaterials.2017.11.014
Abstract

Resistance to platinum agents is challenging in cancer treatment with platinum drugs. Such resistant cells prevent effective platinum accumulation intracellular and alter cellular adaptations to survive from cytotoxicity by regulating corresponding proteins expression. Ideal therapeutics should combine resolution to these pump and non-pump relevant resistance of cancer cells to achieve high efficacy and low side effect. Fe3O4 nanocarrier loaded with drugs could enter cells in a more efficient endocytosis manner which circumvents pump-relevant drug resistance. EZH2 protein which was previously found to be over-expressed in drug-resistant cancer cells was reported to be involved in platinum drug resistance and play a vital role in anti-apoptosis pathways. Here, we report Fe3O4 nanoparticles loaded with siEZH2 (siRNA), a platinum prodrug in +4 oxidation state (cis, cis, trans-diamminedichlorodisuccinato-platinum-(IV), namely Pt(IV)) and luteinizing hormone-releasing hormone (LHRH) targeting polypeptides. Results show that targeted nanoparticles loading with siEZH2 synergize with Pt(IV) and result in similar cell killing performance to A2780/DDP cells (cisplatin resistant) compared with non-siEZH2 loaded nanoparticles to A2780 cells (cisplatin sensitive). Thus, this Fe3O4@PEI-Pt(IV)-PEG-LHRH@siEZH2 nanoparticles reverse the cisplatin resistance from the pump and non-pump relevant aspects, fully taking advantage of nanocarrier system.

Citation C. Yu; B. Ding; X. Zhang; X. Deng; K. Deng; Z. Cheng; B. Xing; D. Jin; P.'an Ma; J. Lin.Targeted iron nanoparticles with platinum-(IV) prodrugs and anti-EZH2 siRNA show great synergy in combating drug resistance in vitro and in vivo.. Biomaterials. 2018;155:112123. doi:10.1016/j.biomaterials.2017.11.014

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Platinum

See more Platinum products. Platinum (atomic symbol: Pt, atomic number: 78) is a Block D, Group 10, Period 6 element with an atomic weight of 195.084. The number of electrons in each of platinum's shells is [2, 8, 18, 32, 17, 1] and its electron configuration is [Xe] 4f14 5d9 6s1. The platinum atom has a radius of 139 pm and a Van der Waals radius of 175 pm. Platinum Bohr ModelElemental PlatinumPlatinum was discovered and first isolated by Antonio de Ulloa in 1735. It is one of the rarest elements in the earth's crust, occurring at a concentration of only 0.005 ppm. Platinum is found uncombined as a free element and alloyed with iridium as platiniridium. In its elemental form, platinum has a grayish white appearance. It is highly resistant to corrosion: the metal does not oxidize in air at any temperature. It is generally non-reactive, even at high temperatures. The origin of the name "platinum" comes from the Spanish word platina, meaning silver.

Iron

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