Redox-sensitive nanoscale drug delivery systems for cancer treatment

Mirhadi, Elaheh; Mashreghi, Mohammad; Maleki, Mahdi Faal; Alavizadeh, Seyedeh Hoda; Arabi, Leila; Badiee, Ali; Jaafari, Mahmoud Reza

doi:10.1016/j.ijpharm.2020.119882

Cited by 81 publications

(43 citation statements)

References 259 publications

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“…Cells hold redox couples, such as GSSG/2GSH, and respond to electron flow, thus affecting many redox-dependent biochemical procedures. Glutathione (GSH) is the dominant thiol-disulfide redox buffer of the cell, 38,39 and cytoplasmic GSH can induce the break of reduction-sensitive bonds. Specifically, it induces the controlled release of the drug/biocargo in the cytoplasm, 39 due to the rapid reduction of disulfide bonds, namely, GSH-exchangeable disulfides.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Glutathione (GSH) is the dominant thiol-disulfide redox buffer of the cell, 38,39 and cytoplasmic GSH can induce the break of reduction-sensitive bonds. Specifically, it induces the controlled release of the drug/biocargo in the cytoplasm, 39 due to the rapid reduction of disulfide bonds, namely, GSH-exchangeable disulfides. 40 Protein thiolation/dethiolation is involved in cell signaling pathways, affects activities like ligand and DNA binding, and depends on cell redox control.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Intracellular targets: A multiple cargo transporting molecule

Papadopoulos

Fotou

Moussis

et al. 2021

Journal of Peptide Science

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Peptide analogs/conjugates Abbreviation Ac-(Lys-Aib-Cys) 4 -NH 2 CPSOC CF-Ahx-[Lys-Aib-Cys(S-CH 2 CONH 2 )] 4 -NH 2 CF-Ahx-CPSOC(S-CH 2 CONH 2 ) CF-G 48 RKKRRQRRRPPQ 60 -Cys (CH 2 CONH 2 )-NH 2 CF-Tat 48-60 -Cys (CH 2 CONH 2 ) CF-Ahx-S 158 ALTQKGLKNVFDEA 172 -NH 2 CF-Ahx-Cdc42 158-172 CF-Ahx-[Lys-Aib-Cys(S-CH 2 CO-V 181 IKKSKK 187 -NH 2 )] 4 -NH 2 CF-Ahx-CPSOC(S-CH 2 CO-Cdc42 181-187 ) CF-Ahx-[Lys-Aib-Cys(S-CH 2 CO-I 173 VAALEPPVIKKSKK 187 -NH 2 )] 4 -NH 2 CF-Ahx-CPSOC(S-CH 2 CO-Cdc42 173-187

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Section: Future Perspectivesmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Intracellular targets: A multiple cargo transporting molecule

Papadopoulos

Fotou

Moussis

et al. 2021

Journal of Peptide Science

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“…Presently, immune checkpoint inhibitors are commonly used for cancer therapy in several cancers, and ROS is closely associated with the tumor microenvironment and immunity [9]. ROS accumulation has been suggested to be associated with the anticancer effects of these compounds, including induction of cell death and prolongation of survival periods in gastric cancer and lung cancer [167,168].…”

Section: Mitochondrial Ros In Immune Therapymentioning

confidence: 99%

“…Under normal physiological conditions, this substance participates in the maintenance of metabolic homeostasis, and exhibits regulatory roles in proliferation and differentiation [2][3][4]. During the last two decades, numerous in vivo and in vitro studies have supported the opinion that dysregulation of ROS plays an important role in the etiology and pathology of diseases such as vascular disease, diabetes, and malignant tumors by damaging cellular components, and in the pharmacological mechanisms of therapeutics [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

et al. 2020

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Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.

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“…Moreover, CB [7] enabled the noncovalent supramolecular assembly between the self-assembly units of PG-Pt-LA nanoparticles (NPs), which was schemed to disassemble due to the overexpressed spermine in tumor microenvironment tissue. Leadingly, this novel size-transformable supramolecular nanomedicine possessed persistent circulation in the bloodstream and enhanced tumor accumulation by means of enhanced permeation and retention (EPR) effect 15 , as well as promoted tumor penetration upon disassociation in presence of spermine. Of note, the disassembling of PG-Pt-LA/CB [7] NPs in responsive to spermine, as well as the reduction of OxPt-COOH by glutathione (GSH) in CRC microenvironment will alleviate the non-speci c toxicity of OxPt.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular nanomedicine for enhanced chemotherapy against drug-resistant colorectal cancer

Yan

Chen

et al. 2021

Preprint

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The presence of Fusobacterium nucleatum (F. nucleatum) in the community of colorectal cancer (CRC) accounts for its chemotherapy resistance, which underlies the clinical failure of chemotherapeutics in the treatment of CRC. To resolve this drawback, we manufactured a novel multifaceted supramolecular nanomedicine capable of eliminating F. nucleatum, minimizing the non-specific toxicity to normal tissues, and maximizing anti-tumor efficacy. The supramolecular nanomedicine was constructed by conjugating lauric acid (LA) and platinum (IV) oxaliplatin prodrug (OxPt-COOH) to hyperbranched poly(glycidol) (PG), followed by addition of cucurbit[7]uril (CB[7]) to elicit supramolecular assembly. In principle, LA is schemed to eliminate the F. nucleatum in CRC, thereby enhancing chemotherapeutic efficacy of OxPt. CB[7] facilitates host − guest complexation with OxPt, allowing its activation specifically in the spermine-overexpressed CRC tumors and thus reducing the potential toxicity to normal tissues. Moreover, CB[7] conduces to supramolecular assembly between the self-assembly units of PG-Pt-LA nanoparticles, representing a novel size-transformable supramolecular nanomedicine (PG-Pt-LA/CB[7]), whose hydrodynamic diameter is approximately 200 nm in blood circulation and decreases to approximately 10 nm upon arrival at tumors due to its responsiveness to spermine, which can address the dilemma of long circulation and deep penetration existed in nanomedicine. In vivo investigations reveal that our proposed supramolecular nanomedicine possesses prolonged blood circulation, enhanced permeation and retention effect in tumors. In F. nucleatum co-localized HT29 mouse model, PG-Pt-LA/CB[7] is validated to be a targeted, safe and effective nanomedicine that substantially promoted the chemotherapeutic efficacy in the treatment of drug-resistant CRC through inhibiting autophagy induced by F. nucleatum. These findings demonstrate our multifaceted supramolecular nanomedicine can effectively overcome drug resistance of chemotherapy caused by bacteria, providing a valid strategy for clinic treatment of intractable CRC.

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Redox-sensitive nanoscale drug delivery systems for cancer treatment

Cited by 81 publications

References 259 publications

Intracellular targets: A multiple cargo transporting molecule

Intracellular targets: A multiple cargo transporting molecule

Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

Supramolecular nanomedicine for enhanced chemotherapy against drug-resistant colorectal cancer

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