Singh Aakriti, Sharma Sandeep, Yadagiri Ganesh, Parvez Shabi, Gupta Ritika, Singhal Nitin Kumar, Koratkar Nikhil, Singh Om Prakash, Sundar Shyam, Shanmugam Vijayakumar, Mudavath Shyam Lal
Infectious Disease Biology Laboratory, Chemical Biology Unit, Institute of Nano Science and Technology, Habitat Centre Phase-10, Sector-64 Mohali Punjab 160062 India
Institute of Nano Science and Technology, Habitat Centre Phase-10, Sector-64, Mohali Punjab 160062 India
RSC Adv. 2020 Jul 22;10(46):27502-27511. doi: 10.1039/d0ra04266h. eCollection 2020 Jul 21.
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 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 -infected macrophages, generating unfavourable conditions for the amastigote, and thus improving its efficacy.
是一种专性细胞内原生动物寄生虫，寄生于被称为寄生泡的人类巨噬细胞液泡中。两性霉素B（AmB）是一线药物，治愈率达99%；然而，过量引起的毒副作用是一个主要限制因素。为了在较低剂量下提高疗效，进而避免毒性，并进一步研究电荷动力学对疗效的作用，用天然带负电荷的氧化石墨烯（GO）和胺共轭带正电荷的AGO制备了基于GO的AmB复合材料。共聚焦和流式细胞术分析证实，AGO复合材料的摄取增强。因此，AGO对无鞭毛体有强烈抑制作用，其IC值比游离AmB低5倍。寄生泡具有水解和酸性环境，这对寄生虫有利，因为它们不会减弱这种条件。AGO-AmB能够改变被感染巨噬细胞的细胞内pH值，为无鞭毛体创造不利条件，从而提高其疗效。
