• 文献标题:   Sensible graphene oxide differentiates macrophages and Leishmania: a bio-nano interplay in attenuating intracellular parasite
  • 文献类型:   Article
  • 作  者:   SINGH A, SHARMA S, YADAGIRI G, PARVEZ S, GUPTA R, SINGHAL NK, KORATKAR N, SINGH OP, SUNDAR S, SHANMUGAM V, MUDAVATH SL
  • 作者关键词:  
  • 出版物名称:   RSC ADVANCES
  • ISSN:  
  • 通讯作者地址:   Inst Nano Sci Technol
  • 被引频次:   0
  • DOI:   10.1039/d0ra04266h
  • 出版年:   2020

▎ 摘  要

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 IC50 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.