524 research outputs found

    Redox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania

    No full text
    Leishmaniasis, a vector-borne disease, is caused by intracellular parasite Leishmania donovani. Unlike most intracellular pathogens, Leishmania donovani are lodged in parasitophorous vacuoles and replicate within the phagolysosomes in macrophages. Effective vaccines against this disease are still under development, while the efficacy of the available drugs is being questioned owing to the toxicity for nonspecific distribution in human physiology and the reported drug-resistance developed by Leishmania donovani. Thus, a stimuli-responsive nanocarrier that allows specific localization and release of the drug in the lysosome has been highly sought after for addressing two crucial issues, lower drug toxicity and a higher drug efficacy. We report here a unique lysosome targeting polymeric nanocapsules, formed via inverse mini-emulsion technique, for stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line. A benign polymeric backbone, with a disulfide bonding susceptible to an oxidative cleavage, is utilized for the organelle-specific release of miltefosine. Oxidative rupture of the disulfide bond is induced by intracellular glutathione (GSH) as an endogenous stimulus. Such a stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line over a few hours helped in achieving an improved drug efficacy by 200 times as compared to pure miltefosine. Such a drug formulation could contribute to a new line of treatment for leishmaniasis.A. Das acknowledges SERB (India) Grants (CRG/2020/000492 and JCB/2017/000004) and DBT Grant (BT/PR22251/NNT/28/1274/2017) for supporting this research. N. Mukherjee acknowledges SERB (India) Grant PDF/2016/001437 and K. Das acknowledges the grant EMR/2015/001674 for supporting this research. Financial support from DST (DST/INSPIRE/03/2017/002477) is acknowledged by R.T. This manuscript bears CSMCRI registration no 7/2021.Pramanik, SK (corresponding author), CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India. Mukherjee, N (corresponding author), CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, Kolkata 700032, India. Chattopadhy, S (corresponding author), BITS Pilani, Pilani 403726, Goa, India. Das, A (corresponding author), Indian Inst Sci Educ & Res Kolkata, Mohanpur 741246, W Bengal, India. [email protected]; [email protected]; [email protected]

    Programmed exosome fusion for energy generation in living cells

    No full text
    © 2021, The Author(s), under exclusive licence to Springer Nature Limited.Biological membrane-enclosed organelles are fascinating examples of spatially confined nanoreactors for biocatalytic transformations such as cascade reactions involving multiple enzymes; however, the fabrication of their synthetic mimics remains a considerable challenge. Here we demonstrate supramolecular chemistry-based bridging of two membranes leading to controlled fusion of exosomes that act as nanoreactors for effective biocatalytic cascades, with prolonged functionality inside of living cells. Exosome membrane proteins were chemically engineered with a catechol moiety to drive fusion by supramolecular complexation to bridge the membranes. This strategy successfully encapsulated multiple enzymes and assembled the minimal electron transport chain in the plasma membrane, leading to tuneable, enhanced catalytic cascade activity capable of ATP synthesis inside of tissue spheroids. This nanoreactor was functional for many hours after uptake into living cells, showed successful penetration into tissue spheroids and repaired the damaged region by supplying ATP, all of which represent an advance in the mimicking of nature’s own organelles. [Figure not available: see fulltext.].11Nsciescopu

    Nanocapsules with stimuli-responsive moieties for controlled release employing light and enzymatic triggers

    No full text
    The development of stimuli-responsive nanomaterials, that possess tailored functional properties for the release of specific compounds, is of particular interest. To this extent, controlling the release of molecules at the desired target is an important parameter to regulate chemical and/or biological reactions at a more profound level in a wide variety of applications. In the present work, we report on the development of dual-responsive thiourethane-urethane nanocapsules synthesizedviaan interfacial polymerization reaction executed at the droplet interface using the inverse miniemulsion technique. Evidenceviamorphological and controlled release investigations indicate that our nanocapsules are able to encapsulate hydrophilic compounds with high efficiency in their aqueous core and allow for its selective release upon exposure to UV light and the enzyme esterase. Moreover, we demonstrate the efficient encapsulation of the fragrance molecule geranyl acetate and the anticancer drug doxorubicin. For the latter, we demonstrate its apoptotic effect after being released in MCF 7 breast cancer cells. Overall, these nanocapsules can be used for a wide variety of applications where a selective release of the payload is desired.S. S. is an SB PhD Fellow at the FWO (Research Foundation Flanders). S. K. P. acknowledges BOF funding from Hasselt University. This work is supported by Hasselt University and the Research Foundation Flanders (FWO Vlaanderen; Hercules project AUHL/15/2 - GOH3816N). The authors are thankful to Prof. M. Van Bael for access to the DLS device.Pramanik, SK; Ethirajan, A (corresponding author), Hasselt Univ, Inst Mat Res IMO, Wetenschapspk 1 & Agoralaan D, B-3590 Diepenbeek, Belgium; IMEC, Associated Lab IMOMEC, Wetenschapspk 1, B-3590 Diepenbeek, Belgium; CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India. [email protected]; [email protected]
    corecore