Sensible graphene oxide differentiates macrophages and Leishmania: a bio-nano interplay in attenuating intracellular parasite. Issue 46 (22nd July 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: RSC advances. Volume 10:Issue 46(2020)
• Page Start: 27502
• Page End: 27511
• Publication Date: 2020-07-22
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra04266h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : AGO-AmB nanocomposites as a potential therapeutic anti-leishmanial agents. Abstract : 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.