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


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.

SUBMITTER: Singh A 

PROVIDER: S-EPMC9055620 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Sensible graphene oxide differentiates macrophages and <i>Leishmania</i>: a bio-nano interplay in attenuating intracellular parasite.

Singh Aakriti A   Sharma Sandeep S   Yadagiri Ganesh G   Parvez Shabi S   Gupta Ritika R   Singhal Nitin Kumar NK   Koratkar Nikhil N   Singh Om Prakash OP   Sundar Shyam S   Shanmugam Vijayakumar V   Mudavath Shyam Lal SL  

RSC advances 20200722 46


<i>Leishmania</i> 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 wit  ...[more]

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