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Sensible graphene oxide differentiates macrophages and Leishmania: a bio-nano interplay in attenuating intracellular parasite

机译:合理的石墨烯氧化物区分巨噬细胞和莱山米:生物纳米在减少细胞内寄生虫中的相互作用

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Leishmania is an obligate intracellular protozoan parasite, which resides in human macrophage vacuoles that are referred to as parasitophorus vacuoles. Amphotericin B (AmB) is the first-line drug with 99% cure rates; however, overdose-induced toxic side effects are a major limitation. To improve the efficacy at lower dose and subsequently to avoid toxicity and to further investigate the role of charge dynamics on the efficacy, a graphene oxide (GO)-based composite of AmB was developed with native negatively charged GO and amine-conjugated positively charged AGO. The AGO composite resulted in enhanced uptake as confirmed by confocal and FACS analysis. Thus, AGO caused a strong inhibition of amastigotes, with IC _(50) values 5-fold lower than free AmB. The parasitophorus vacuoles harbour a hydrolytic and acidic environment, which is favourable for the parasites, as they don't attenuate this condition. AGO–AmB was able to modify the intracellular pH of the Leishmania donovani -infected macrophages, generating unfavourable conditions for the amastigote, and thus improving its efficacy.
机译:Leishmania是一种迫使细胞内原生动物寄生虫,其存在于人巨噬细胞液泡中称为胰腺炎植物。两性霉素B(AMB)是一排药物,固化率为99%;然而,过量诱导的有毒副作用是一个主要限制。为了提高较低剂量的疗效,随后避免毒性,并进一步研究充电动力学对疗效的作用,并在AMB的基础上进行了基础的氧化石墨烯(GO)的综合,并积极收取胺缀合的胺。以前,Composite导致增强的摄取,通过共聚焦和FACS分析确认。因此,以前引起了对Amastigotes的强烈抑制,IC _(50)值比自由伏夫低5倍。寄生虫液泡含有水解和酸性环境,这对寄生虫有利,因为它们不会衰减这种情况。以前-BAM能够改变Leishmania Donovani-infed巨噬细胞的细胞内pH值,为Amastigotoote产生不利的条件,从而提高其疗效。

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