Sensible graphene oxide differentiates macrophages and Leishmania: a bio-nano interplay in attenuating intracellular parasite
2020
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
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.
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