Reversal of doxorubicin resistance in breast cancer by mitochondria-targeted pH-responsive micelles

Yu, Peng; Yu, Haijun; Guo, Chengyue; Cui, Zhiwen; Chen, Xianzhi; Yin, Qi; Zhang, Pengcheng; Yang, Xiangliang; Cui, Honggang; Li, Yaping

doi:10.1016/j.actbio.2014.12.001

Cited by 119 publications

(66 citation statements)

References 33 publications

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“…Doxorubicin is a widely used drug in diverse types of cancer diseases and is also cytotoxic to normal cells (Malek et al, 2011). Our results shows that compound 1 have less cytotoxic effect than Doxorubicin (IC 50 = 5.52 M) in MCF-7 after 24 h of exposure (Yu et al, 2015).…”

Section: Cytotoxic Activitymentioning

confidence: 90%

Fast isolation of cytotoxic compounds from the native Chilean species Gypothamnium pinifolium Phil. collected in the Atacama Desert, northern Chile

Simirgiotis

Bórquez

Neves-Vieira

et al. 2015

Industrial Crops and Products

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Section: Cytotoxic Activitymentioning

confidence: 90%

Fast isolation of cytotoxic compounds from the native Chilean species Gypothamnium pinifolium Phil. collected in the Atacama Desert, northern Chile

Simirgiotis

Bórquez

Neves-Vieira

et al. 2015

Industrial Crops and Products

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“…Thus, instead of hydrophobic Dox, a hydrophobic Nile red (NR) was used because the fl uorescence of the NR is emitted in hydrophobic environments (e.g., the hydrophobic compartment of NPs) but is quenched in polar environments (e.g., water). [ 26 ] In the dialysis device, the Dox·HCl was completely permeated within 6 h, whereas the Dox·HCl released from the Dox·HCl-loaded TPCL NPs was approximately fi vefold slower to fully permeate ( Figure 6 a). Particularly, although the release of Dox·HCl was not signifi cantly affected by the NP preparations, the Dox·HCl-TPCL1 NPs exhibited slightly faster Dox·HCl release than the Dox·HCl-TPCL2 NPs.…”

Section: Physicochemical Characteristics and Drug Release Of Drug-loamentioning

confidence: 97%

Triphenylphosphonium‐Conjugated Poly(ε‐caprolactone)‐Based Self‐Assembled Nanostructures as Nanosized Drugs and Drug Delivery Carriers for Mitochondria‐Targeting Synergistic Anticancer Drug Delivery

Cho

Kwon

et al. 2015

Adv Funct Materials

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For mitochondria‐targeting delivery, a coupling reaction between poly(ε‐caprolactone) diol (PCL diol) and 4‐carboxybutyltriphenylphosphonium (4‐carboxybutyl TPP) results in the synthesis of amphiphilic TPP‐PCL‐TPP (TPCL) polymers with a bola‐like structure. In aqueous environments, the TPCL polymer self‐assembled via cosolvent dispersion and film hydration, resulting in the formation of cationic nanoparticles (NPs) less than 50 nm in size with zeta‐potentials of approximately 40 mV. Interestingly, different preparation methods for TPCL NPs result in various morphologies such as nanovesicles, nanofibers, and nanosheets. In vitro cytotoxicity results with TPCL NPs indicate IC50 values of approximately 10–60 μg mL−1, suggesting their potential as anticancer nanodrugs. TPCL NPs can be loaded both with hydrophobic doxorubicin (Dox) and its hydrophilic salt form (Dox·HCl), and their drug loading contents are approximately 2–10 wt% depending on the loading method and the hydrophilicity/hydrophobicity of the drugs. Although Dox·HCl exhibits more cellular and nuclear uptake, resulting in greater antitumor effects than Dox, most drug‐loaded TPCL NPs exhibit higher mitochondrial uptake and approximately 2–7‐fold higher mitochondria‐to‐nucleus preference than free drugs, resulting in superior (approximately 7.5–18‐fold) tumor‐killing activity for most drug‐loaded TPCL NPs compared with free drugs. In conclusion, TPCL‐based nanoparticles have potential both as antitumor nanodrugs themselves and as nanocarriers for chemical therapeutics.

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“…The change in MMP was correlated with intracellular ATP depletion in MCF-7/ADR cells treated with TPGS or TPGS 2K. The MMP decrease and cellular ATP depletion induced by TPGS could be ascribed to the specific interaction of TPGS with mitochondrial organelles 43. It was reported that VES and some VES analogs could interfere with the ubiquinone-binding sites of mitochondrial complex II in the…”

mentioning

confidence: 97%

Micelles of d-α-Tocopheryl Polyethylene Glycol 2000 Succinate (TPGS 2K) for Doxorubicin Delivery with Reversal of Multidrug Resistance

Hao

Chen

Liu

et al. 2015

ACS Appl. Mater. Interfaces

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The purpose of this study is to investigate the ability of doxorubicin (DOX)-loaded d-α-tocopheryl polyethylene glycol 2000 succinate (TPGS 2K) micelles to overcome MDR in breast cancer treatment. The DOX-loaded TPGS 2K micelles exhibited an average size of around 23 nm, a near neutral zeta potential of around 4 mv and high encapsulation efficiency (85.22 ± 1.89%). The TPGS 2K conjugate did not have significant influences on the reduction of mitochondrial membrane potential (MMP) and the depletion of intracellular ATP level of MCF-7/ADR cells but had an evident effect on the inhibition of Verapamil-induced P-gp ATPase activity. In vitro cell culture experiments demonstrated the DOX-loaded TPGS 2K micelles, resulting in higher cellular uptake and more significant cytotoxicity effect against MCF-7/MDR cells than the free DOX solution. Additionally, the in vivo imaging study revealed DiR-loaded TPGS 2K micelles distributed selectively in MCF-7/ADR tumor-bearing nude mice and had a sufficient residence time. In the anticancer efficacy test with MCF-7/ADR tumor bearing nude mice, the DOX-loaded TPGS 2K micelles displayed significantly higher antitumor activity compared with free DOX solution at the same DOX dosage but less toxicity evaluated by the change of body weight and histological examination. Therefore, this drug delivery micellar system based on TPGS 2K conjugates can serve as a potential nanomedicine for reversing MDR.

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Reversal of doxorubicin resistance in breast cancer by mitochondria-targeted pH-responsive micelles

Cited by 119 publications

References 33 publications

Fast isolation of cytotoxic compounds from the native Chilean species Gypothamnium pinifolium Phil. collected in the Atacama Desert, northern Chile

Fast isolation of cytotoxic compounds from the native Chilean species Gypothamnium pinifolium Phil. collected in the Atacama Desert, northern Chile

Triphenylphosphonium‐Conjugated Poly(ε‐caprolactone)‐Based Self‐Assembled Nanostructures as Nanosized Drugs and Drug Delivery Carriers for Mitochondria‐Targeting Synergistic Anticancer Drug Delivery

Micelles of d-α-Tocopheryl Polyethylene Glycol 2000 Succinate (TPGS 2K) for Doxorubicin Delivery with Reversal of Multidrug Resistance

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