Superior proapoptotic activity of curcumin-loaded mixed block copolymer micelles with mitochondrial targeting properties

Momekova, Denitsa; Ugrinova, Iva; Slavkova, Marta; Momekov, Georgi; Grancharov, Georgy; Gancheva, Valeria; Petrov, Petar

doi:10.1039/c8bm00644j

Cited by 18 publications

(14 citation statements)

References 29 publications

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“…Such pharmacological success relies on the phytochemical abilities of acting on many critical pathways, showing anti-inflammatory (Tham et al, 2010), anti-oxidant (Alexandrow et al, 2012), anti-microbial (Moghadamtousi et al, 2014), and anti-apoptotic (Yu et al, 2010; Jaisin et al, 2011) effects, as well as capability to promote stem cell differentiation (Gu et al, 2012; Mujoo et al, 2012; Chen et al, 2014). Effects of curcumin on mitochondrial function have also been reported (Bavarsad et al, 2018; He et al, 2018; Hsiao et al, 2018; Momekova et al, 2018; Naserzadeh et al, 2018) and furthermore, hormetic effects of curcumin are receiving increased attention (Moghaddam et al, 2018). Curcumin pleiotropic activity is due to its chemical structure, and specifically to the o-methoxy phenolic groups (Priyadarsini and Indira, 2014), which are central for chemical reactions.…”

Section: Introductionmentioning

confidence: 99%

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Rocha‐Ferreira

Sisa²,

Bright³

et al. 2019

Front. Physiol.

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Hypoxic-ischemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1,000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE. Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumor and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilize the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects. Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis, and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200 μg/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60 or 120 min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin’s anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity. In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance.

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Section: Introductionmentioning

confidence: 99%

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Rocha‐Ferreira

Sisa²,

Bright³

et al. 2019

Front. Physiol.

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“…Adopting a similar strategy by using a micellar drug delivery system, Momekova et al developed a curcumin‐loaded drug nanocarrier [64] . The micelles were formed by the co‐assembly of two amphiphilic triblock copolymers, PEG‐PCL‐PEG and PDMAEMA TPP ‐PCL‐PDMAEMA TPP .…”

Section: Smart Design Strategiesmentioning

confidence: 99%

“…As such, ensuring cancer‐cell‐specific delivery of nanocarriers reduces toxicity to normal tissues. Next, upon intracellular delivery via receptor‐mediated endocytosis or transporters and under subsequent endogenous stimulation such as pH, [64, 65, 69] endogenous glutathione (GSH), [63, 70] and enzymes, [49, 51f] the ligand‐coated outer shell can be detached and removed, allowing sequential targeting of the nanocarrier to mitochondria.…”

Section: Smart Design Strategiesmentioning

confidence: 99%

Smart Design of Nanomaterials for Mitochondria‐Targeted Nanotherapeutics

et al. 2020

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Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular‐targeting drug‐delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multifunctional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli‐responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this Review, we survey the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria‐targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondrial‐targeting nanotherapeutics.

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“…Momekova et al. entwickelten einen mit Curcumin beladenen Wirkstoffnanocarrier, indem sie eine ähnliche Strategie unter Verwendung eines mizellaren Wirkstoffabgabesystems verwendeten [64] . Die Mizellen wurden durch Co‐Assemblierung zweier amphiphiler Triblock‐Copolymere, PEG‐PCL‐PEG and PDMAEMA TPP ‐PCL‐PDMAEMA TPP , hergestellt.…”

Section: Intelligente Designstrategienunclassified

“…Momekova et al entwickelten einen mit Curcumin beladenen Wirkstoffnanocarrier,i ndem sie eine ähnliche Strategie unter Verwendung eines mizellaren Wirkstoffabgabesystems verwendeten. [64] Die Mizellen wurden durch Co-Assemblierung zweier amphiphiler Tr iblock-Copolymere,PEG-PCL-PEG and PDMAEMA TPP -PCL-PDMAEMA TPP ,h ergestellt. Bei diesem Design wurden PDMAEMA-Ketten mit TPP-Liganden inkorporiert, um zunächst positiv geladene Corona-Schichten zu bilden, während die äußere Corona den Carrier vor dem biologischen Milieu maskiert.…”

Section: üBerwindung Physiologischer Barrierenunclassified

Intelligentes Design von Nanomaterialien für Mitochondrien‐gerichtete Nanotherapeutika

et al. 2020

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Mitochondrien sind die Kraftwerke der Zelle. Sie sind überlebenswichtige Organellen, die zelluläre Funktionen und den Metabolismus aufrechterhalten. Eine Dysfunktion der Mitochondrien führt zu verschiedenen Krankheiten mit einer großen Diversität klinischer Erscheinungen. In der Vergangenheit wurden Strategien zur Herstellung subzellulär angreifender Nanowirkstoffcarrier entwickelt, die zunächst die zelluläre Internalisierung und schließlich die Lokalisierung der Organelle ermöglichen. Seit einiger Zeit zeichnen sich innovative Strategien für das intelligente Design multifunktionaler Nanocarrier ab. Hierarchisches Targeting erlaubt es diesen, verschiedenste Barrieren auf dem Wege der Verabreichung in vivo zu umgehen oder zu überwinden und das Organell mit guter Bioverfügbarkeit zu erreichen. Stimuli‐responsive Nanocarrier erlauben die kontrollierte Freisetzung der Therapeutika unmittelbar am gewünschten Target. Synergetische Therapien können durch die Verwendung einer Ansatzkombination erzielt werden, wie etwa aus Chemo‐, Gen‐ und Phototherapie. In diesem Aufsatz untersuchen wir dieses Feld auf neuste Entwicklungen und Strategien im intelligenten Design von Nanocarriern für Mitochondrien‐gerichtete Therapeutika. Überdies werden bestehende Herausforderungen sowie bisher unerforschte therapeutische Möglichkeiten aufgezeigt und diskutiert, um die nächste Generation mitochondrial‐gerichteter Nanotherapeutika zu inspirieren.

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Superior proapoptotic activity of curcumin-loaded mixed block copolymer micelles with mitochondrial targeting properties

Abstract: Multifunctional micelles based on two co-assembled block copolymers are proven to effectively accumulate and deliver curcumin in mitochondria, thus, inducing a much higher proapoptotic activity than single copolymer micelles.

Cited by 18 publications

References 29 publications

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Smart Design of Nanomaterials for Mitochondria‐Targeted Nanotherapeutics

Intelligentes Design von Nanomaterialien für Mitochondrien‐gerichtete Nanotherapeutika

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