Engineering of stimuli-sensitive nanopreparations to overcome physiological barriers and cancer multidrug resistance

Ağardan, N. Başaran Mutlu; Torchilin, Vladimir P.

doi:10.1016/b978-0-323-41532-3.00001-4

Cited by 8 publications

(4 citation statements)

References 138 publications

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“…Whereas nano-carrier degradation by lysosome microenvironment and liberation of the active substance may still be considered one important principle of nanoparticle-based drug delivery systems, lysosome membrane can act as a natural barrier against efficient drug release 46 . In this case, cytosolic delivery of the drugs by nanoparticles escaping lysosomal entrapment 47,48 might be a key to successful killing of the cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin

Popescu

Savu²,

Dorobantu³

et al. 2020

Sci Rep

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The purpose of this study was to construct and characterize iron oxide nanoparticles (IONP co) for intracellular delivery of the anthracycline doxorubicin (DOX; IONP DOX) in order to induce tumor cell inactivation. More than 80% of the loaded drug was released from IONP DOX within 24 h (100% at 70 h). Efficient internalization of IONP DOX and IONP co in HeLa cells occurred through pino-and endocytosis, with both IONP accumulating in a perinuclear pattern. IONP co were biocompatible with maximum 27.9% ± 6.1% reduction in proliferation 96 h after treatment with up to 200 µg/mL ionp co. Treatment with IONP DOX resulted in a concentration-and time-dependent decrease in cell proliferation (IC 50 = 27.5 ± 12.0 μg/mL after 96 h) and a reduced clonogenic survival (surviving fraction, SF = 0.56 ± 0.14; versus IONP co (SF = 1.07 ± 0.38)). Both IONP constructs were efficiently internalized and retained in the cells, and IONP DOX efficiently delivered DOX resulting in increased cell death vs ionp co. Chemotherapy is an essential systemic component in modern multimodal cancer treatment, yet one of the main disadvantages of anticancer chemotherapeutics is toxicity to the normal tissue. The use of nano-sized carriers as intracellular transporters for the active substances not only promises to reduce the total drug amount administered, while potentially improving the treatment's efficiency by enhancing the local dose in the tumour, but also can help to improve the specificity and targeting of the active substance, thereby reducing the side-effects associated with chemotherapy 1. In nano-carriers, drugs can be transported to the tumour site through the enhanced permeability and retention effect 2-4 , magnetic targeting 5-8 and protected until they find a triggering stimuli to release, like pH variations 9-12 , temperature 13,14 , radiation-induced release 15-19. The use of iron oxide nanoparticles in the construction of nano-systems for the delivery of chemotherapeutics not only enables active magnetic targeting to the tumour site, but also offers additional functions that make them suitable for diagnosis (contrast substance in MRI 20-22) or enhanced anticancer activity using hyperthermia 23. Conjugation with other compounds can add to the multi-functionality of these nanomaterials and implement properties such as increased and/or specific 24-26 internalization in cancer cells, but can also help to modulate the

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Section: Discussionmentioning

confidence: 99%

Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin

Popescu

Savu²,

Dorobantu³

et al. 2020

Sci Rep

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“…In addition, as shown in Fig. 2 , effective cellular uptake and successful endo/lysosomal escape, which exerted important roles on the therapeutic effects of nanoparticle/pDNA complexes, were observed [ 51 , 52 ]. To date, a wide variety of materials have been used for gene delivery, mainly including polymeric materials, polyethylenimine (PEI), inorganic materials, and numerous cationic lipid materials [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

ROS-responsive nanoparticle-mediated delivery of CYP2J2 gene for therapeutic angiogenesis in severe hindlimb ischemia

Gui

Chen

Diao

et al. 2022

Materials Today Bio

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With critical limb ischemia (CLI) being a multi-factorial disease, it is becoming evident that gene therapy with a multiple bio-functional growth factor could achieve better therapeutic outcomes. Cytochrome P450 epoxygenase-2J2 (CYP2J2) and its catalytic products epoxyeicosatrienoic acids (EETs) exhibit pleiotropic biological activities, including pro-angiogenic, anti-inflammatory and cardiovascular protective effects, which are considerably beneficial for reversing ischemia and restoring local blood flow in CLI. Here, we designed a nanoparticle-based pcDNA3.1-CYP2J2 plasmid DNA (pDNA) delivery system (nanoparticle/pDNA complex) composed of a novel three-arm star block copolymer (3S-PLGA-po-PEG), which was achieved by conjugating three-armed PLGA to PEG via the peroxalate ester bond. Considering the multiple bio-functions of CYP2J2-EETs and the sensitivity of the peroxalate ester bond to H 2 O 2 , this nanoparticle-based gene delivery system is expected to exhibit excellent pro-angiogenic effects while improving the high oxidative stress and inflammatory micro-environment in ischemic hindlimb. Our study reports the first application of CYP2J2 in the field of therapeutic angiogenesis for CLI treatment and our findings demonstrated good biocompatibility, stability and sustained release properties of the CYP2J2 nano-delivery system. In addition, this nanoparticle-based gene delivery system showed high transfection efficiency and efficient VEGF expression in vitro and in vivo. Intramuscular injection of nanoparticle/pDNA complexes into mice with hindlimb ischemia resulted in significant rapid blood flow recovery and improved muscle repair compared to mice treated with naked pDNA. In summary, 3S-PLGA-po-PEG/CYP2J2-pDNA complexes have tremendous potential and provide a practical strategy for the treatment of limb ischemia. Moreover, 3S-PLGA-po-PEG nanoparticles might be useful as a potential non-viral carrier for other gene delivery applications.

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“…Glutathione is both naturally occurring and fortified by diet antioxidants, comprising glycine, cysteine, and glutamic acid [82]. Within the body, it is generated in the cytoplasm and it is found in most tissues, with high concentrations in the liver [83,84]. Glutathione is the major thiol-disulfide redox buffer of the cell, thus playing crucial roles in detoxification and antioxidant mechanisms of the organism [82,84,85].…”

Section: Antioxidant Defense Mechanismmentioning

confidence: 99%

“…Within the body, it is generated in the cytoplasm and it is found in most tissues, with high concentrations in the liver [83,84]. Glutathione is the major thiol-disulfide redox buffer of the cell, thus playing crucial roles in detoxification and antioxidant mechanisms of the organism [82,84,85]. The reactions of glutathione are catalyzed glutathione-S-transferase and they involve the conjugation with aliphatic or aromatic epoxides and halides or organic nitrates, which are further reduced to nitrites [83].…”

Section: Antioxidant Defense Mechanismmentioning

confidence: 99%

Antioxidant Therapies for Neuroprotection—A Review

Teleanu

Chircov

Grumezescu

et al. 2019

JCM

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Although moderate concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are crucial for various physiological processes within the human body, their overproduction leads to oxidative stress, defined as the imbalance between the production and accumulation of ROS and the ability of the body to neutralize and eliminate them. In the brain, oxidative stress exhibits significant effects, due to its increased metabolical activity and limited cellular regeneration. Thus, oxidative stress is a major factor in the progressive loss of neurons structures and functions, leading to the development of severe neurodegenerative disorders. In this context, recent years have witnessed tremendous advancements in the field of antioxidant therapies, with a special emphasis for neuroprotection. The aim of this paper is to provide an overview of the oxidative stress and antioxidant defense mechanisms and to present the most recent studies on antioxidant therapies for neuroprotection.

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Engineering of stimuli-sensitive nanopreparations to overcome physiological barriers and cancer multidrug resistance

Cited by 8 publications

References 138 publications

Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin

Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin

ROS-responsive nanoparticle-mediated delivery of CYP2J2 gene for therapeutic angiogenesis in severe hindlimb ischemia

Antioxidant Therapies for Neuroprotection—A Review

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