I-motif-coated exosomes as a pH-sensitive carrier for anticancer drugs

Kim, Jun Yeong; Song, Jae Bok; Jung, Heejung; Mok, Hyejung

doi:10.1007/s13765-018-0394-0

Cited by 25 publications

(32 citation statements)

References 30 publications

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“…Application of cytosine-rich telomeric fragments of DNA as components of drugs carriers has been described in several studies [16][17][18][19][20][21][22]. This is because such oligonucleotides reveal interesting properties of reversible folding/unfolding in response to pH change.…”

Section: Introductionmentioning

confidence: 99%

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Cytosine-Rich DNA Fragments Covalently Bound to Carbon Nanotube as Factors Triggering Doxorubicin Release at Acidic pH. A Molecular Dynamics Study

Wolski

Nieszporek

Pańczyk

2021

IJMS

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This works deals with analysis of properties of a carbon nanotube, the tips of which were functionalized by short cytosine-rich fragments of ssDNA. That object is aimed to work as a platform for storage and controlled release of doxorubicin in response to pH changes. We found that at neutral pH, doxorubicin molecules can be intercalated between the ssDNA fragments, and formation of such knots can effectively block other doxorubicin molecules, encapsulated in the nanotube interior, against release to the bulk. Because at the neutral pH, the ssDNA fragments are in form of random coils, the intercalation of doxorubicin is strong. At acidic pH, the ssDNA fragments undergo folding into i-motifs, and this leads to significant reduction of the interaction strength between doxorubicin and other components of the system. Thus, the drug molecules can be released to the bulk at acidic pH. The above conclusions concerning the storage/release mechanism of doxorubicin were drawn from the observation of molecular dynamics trajectories of the systems as well as from analysis of various components of pair interaction energies.

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Section: Introductionmentioning

confidence: 99%

“…In another study, Kim et.al. [20] utilized iM modified exosomes as platforms for doxorubicin (DOX) storage and release with iM folding/unfolding property as a key factor for controlled release of DOX. Intercalation of DOX within dsDNA fragments attached to gold nanoparticles was studied in the work by Park et.al.…”

Section: Introductionmentioning

confidence: 99%

Cytosine-Rich DNA Fragments Covalently Bound to Carbon Nanotube as Factors Triggering Doxorubicin Release at Acidic pH. A Molecular Dynamics Study

Wolski

Nieszporek

Pańczyk

2021

IJMS

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“…Several studies using the pH-responsive drug release ability of i-motif system have been reported [6,7,8,9]. An i-motif and G-quadruplex-modified gold nanoparticle (AuNP) was developed for anti-tumor therapy via chemotherapy by DOX, photothermal therapy (PTT) by AuNP, and photodynamic therapy (PDT) by photosensitizer.…”

Section: Introductionmentioning

confidence: 99%

“…In another case, i-motif was grafted on exosome using biotin-streptavidin interaction to deliver DOX by intercalation in their double-stranded structure. In acidic condition, DOX release from exosome was triggered by the formation of i-motif, disintegrating double-stranded DNA structure [9].…”

Section: Introductionmentioning

confidence: 99%

pH-Responsive i-motif Conjugated Hyaluronic Acid/Polyethylenimine Complexes for Drug Delivery Systems

Lee

Kim

2019

Pharmaceutics

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i-motif is cytosine (C)-rich oligonucleotide (ODN) which shows pH-responsive structure change in acidic condition. Therefore, it has been utilized for the trigger of intercalated drug release, responding to environmental pH change. In this study, 2.76 molecules of i-motif binding ODNs (IBOs) were conjugated to each hyaluronic acid (HA) via amide bond linkages. Synthesis of HA-IBO conjugate (HB) was confirmed by FT-IR and agarose gel electrophoresis with Stains-All staining. After hybridization of HB with i-motif ODN (IMO), it was confirmed that doxorubicin (DOX) could be loaded in HB-IMO hybrid structure (HBIM) with 65.6% of drug loading efficiency (DLE) and 25.0% of drug loading content (DLC). At pH 5.5, prompt and significant DOX release from HBIM was observed due to the disruption of HBIM hybrid structure via i-motif formation of IMO, contrary to pH 7.4 condition. Then, HBIM was complexed with low molecular weight polyethylenimine (PEI1.8k), forming positively charged nanostructures (Z-average size: 126.0 ± 0.4 nm, zeta-potential: 16.1 ± 0.3 mV). DOX-loaded HBIM/PEI complexes displayed higher anticancer efficacy than free DOX in A549 cells, showing the potential for pH-responsive anticancer drug delivery systems.

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“…Recently, biologically derived vesicles, e.g., cell-derived vesicles and microvesicles, have been intensively investigated as one of the alternatives for synthetic particulate systems. In particular, exosomes (EXOs) have been considered promising drug carriers because of their aqueous stability, homogeneous diameter, and biocompatibility [11][12][13]. In a previous study, serum derived EXOs had a narrow size distribution of approximately 50 nm as well as high production yield [14].…”

Section: Introductionmentioning

confidence: 99%

Citraconylated exosomes for improved internalization into macrophages

Kim

Mok

2019

Appl Biol Chem

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Considering the close relation between macrophages and inflammatory diseases, the design of carriers for the delivery of drugs, genes, and small molecules into macrophages is crucial. In this study, the surface charge of exosome (EXO) was easily modified to highly negative charge by citraconylation. Prepared citraconylated EXO (cit-EXO) exhibited a significantly reduced surface charge down to − 50 from − 15 mV of EXO surface charge, despite similar hydrodynamic size. In the absence of serum proteins, both EXO and cit-EXO were similarly internalized into RAW264.7 cells and DC2.4 cells. However, cit-EXO exhibited superior intracellular uptake to that of EXO for RAW264.7 cells in the presence of serum proteins because of highly negative charges. However, there were no significant differences in intracellular uptake of EXO and cit-EXO for DC2.4 cells. Taken together, simple surface modification onto EXOs via citraconylation improved delivery of nanosized EXO (~ 50 nm) into macrophages, which could serve as a promising strategy for the development of carriers for efficient macrophage delivery.

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I-motif-coated exosomes as a pH-sensitive carrier for anticancer drugs

Cited by 25 publications

References 30 publications

Cytosine-Rich DNA Fragments Covalently Bound to Carbon Nanotube as Factors Triggering Doxorubicin Release at Acidic pH. A Molecular Dynamics Study

Cytosine-Rich DNA Fragments Covalently Bound to Carbon Nanotube as Factors Triggering Doxorubicin Release at Acidic pH. A Molecular Dynamics Study

pH-Responsive i-motif Conjugated Hyaluronic Acid/Polyethylenimine Complexes for Drug Delivery Systems

Citraconylated exosomes for improved internalization into macrophages

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