Reversing multidrug resistance by intracellular delivery of Pluronic® P85 unimers

Hong, Wei; Chen, Fan; Zhang, Xiaojun; Zeng, Jianfu; Hu, Haiyang; Zhao, Xiuli; Qiao, Mingxi

doi:10.1016/j.biomaterials.2013.08.032

Cited by 82 publications

(55 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…21 In this study, we extended the time period and obtained different results. We detected the intracellular fluorescence intensity of PAMAM-NH 2 at different times (1,3,6,9,12,18, and 24 hours) after its removal. As shown in Figure 9A, the exocytosis of PAMAM-NH 2 in the MCF-7 cells reached a maximum at 3 hours.…”

Section: Exocytosis Of Pamam Dendrimersmentioning

confidence: 99%

“…9 PAMAM-NH 2 dendrimers are able to encapsulate chemotherapeutic drugs in their interior. For example, Yabbarov et al synthesized a three-component delivery system comprising a vector protein (recombinant receptor-binding fragment of Our laboratory has also conducted a number of studies on reversing MDR in cancer 12 and has prepared PAMAM/ HMGB1/pDNA nanocomplexes that can be used as high-efficiency gene carriers in vitro/vivo with high transfection and expression efficiency in sensitive breast cancer cells (MCF-7 cells). 13 We have further applied PAMAM/HMGB1/ pDNA nanocomplexes to multidrug-resistant breast cancer cells (MCF-7/ADR cells).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

Zhang¹,

Liú²,

Zhang³

et al. 2016

IJN

Self Cite

View full text Add to dashboard Cite

Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH 2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH 2 was much lower and exocytosis of PAMAM-NH 2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH 2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH 2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH 2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH 2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH 2 as a drug and gene vector in resistant cells.

show abstract

Section: Exocytosis Of Pamam Dendrimersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

Zhang¹,

Liú²,

Zhang³

et al. 2016

IJN

Self Cite

View full text Add to dashboard Cite

show abstract

“…The micelles showed greater cytotoxicity compared to folate-free micelles. 22 Wang et al designed and prepared a novel drug delivery system, designated S @ L NPs, in which several smaller nanoparticles (NPs) are contained within a larger NP. S @ L NPs could be triggered to degrade and release CS/PAA/VP-16 NPs in the acidic environment of the cytosol, endosomes or lysosomes, and CS/PAA/VP-16 NPs were capable of entering the nucleus through nucleopores, which could enhance the anticancer effect of the loaded drug by inducing autophagy and apoptosis of MDR cells.…”

Section: Introductionmentioning

confidence: 99%

Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells

Hong

Shi

Qiao

et al. 2017

IJN

Self Cite

View full text Add to dashboard Cite

Even though a tremendous number of multifunctional nanocarriers have been developed to tackle heterogeneous cancer cells, little attention has been paid to elucidate how to rationally design a multifunctional nanocarrier. In this study, three individual functions (active targeting, stimuli-triggered release and endo-lysosomal escape) were evaluated in doxorubicin (DOX)-sensitive MCF-7 cells and DOX-resistant MCF-7/ADR cells by constructing four kinds of micelles with active-targeting (AT-M), passive targeting, pH-triggered release ( pH T-M) and endo-lysosomal escape ( endo E-M) function, respectively. AT-M demonstrated the strongest cytotoxicity against MCF-7 cells and the highest cellular uptake of DOX due to the folate-mediated endocytosis. However, AT-M failed to exhibit the best efficacy against MCF-7/ADR cells, while endo E-M exhibited the strongest cytotoxicity against MCF-7/ADR cells and the highest cellular uptake of DOX due to the lowest elimination of DOX from the cells. This was attributed to the carrier-facilitated endo-lysosomal escape of DOX, which avoided exocytosis by lysosome secretion, resulting in an effective accumulation of DOX in the cytoplasm. The enhanced elimination of DOX from the MCF-7/ADR cells also accounted for the remarkable decrease in cytotoxicity against the cells of AT-M. Three micelles were further evaluated with MCF-7 cells and MCF-7/ADR-resistant cells xenografted mice model. In accordance with the in vitro results, AT-M and endo E-M demonstrated the strongest inhibition on the MCF-7 and MCF-7/ADR xenografted tumor, respectively. Active targeting and active targeting in combination with endo-lysosomal escape have been demonstrated to be the primary function for a nanocarrier against doxorubicin-sensitive and doxorubicin-resistant MCF-7 cells, respectively. These results indicate that the rational design of multifunctional nanocarriers for cancer therapy needs to consider the heterogeneous cancer cells and the primary function needs to be integrated to achieve effective payload delivery.

show abstract

“…[44][45][46][47] The effects of these polymers on mitochondrial MP of MCF-7 and MCF-7/PTX cells were determined by JC-1. Once bounded with high MP, JC-1 could be able to reversibly transform from a monomer form (green florescence) to an aggregate form (red florescence).…”

Section: Effects Of Polymers On Mitochondrial Functionmentioning

confidence: 99%

Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Lin¹,

Zhao²,

Liu³

et al. 2018

IJN

View full text Add to dashboard Cite

Introduction The development of nanodrug carriers utilizing tumor microenvironment has become a hotspot in reversing multidrug resistance (MDR). Materials and methods This study synthesized a redox-sensitive copolymer, Pluronic F127-disulfide bond- d -α-tocopheryl polyethylene glycol 1000 succinate (FSST), through the connection of the reduction-sensitive disulfide bond between F127 and d -α-tocopheryl polyethylene glycol 1000 succinate. This polymer could induce the elevation of reactive oxygen species (ROS) levels, ultimately resulting in cytotoxicity. Moreover, the redox-responsive mixed micelles, F127-folate (FA)/FSST/P123 (FFSSTP), based on FSST, Pluronic F127-FA, and Pluronic P123, were prepared to load paclitaxel (PTX). Results The in vitro release study demonstrated that FFSSTP/PTX accelerated the PTX release through the breakage of disulfide bond in reductive environment. In cellular experiment, FFSSTP/PTX induced significant apoptosis in PTX-resistant MCF-7/PTX cells through inhibiting adenosine triphosphate (ATP)-binding cassette proteins from pumping out PTX by interfering with the mitochondrial function and ATP synthesis. Furthermore, FFSSTP/PTX induced apoptosis through elevating the intracellular levels of ROS. Conclusion FFSSTP could become a potential carrier for the treatment of MDR tumors.

show abstract

Reversing multidrug resistance by intracellular delivery of Pluronic® P85 unimers

Cited by 82 publications

References 47 publications

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells

Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Contact Info

Product

Resources

About

Reversing multidrug resistance by intracellular delivery of Pluronic® P85 unimers

Cited by 82 publications

References 47 publications

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells

Redox-responsive F127-folate/F127-disulfide bond-D-&alpha;-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

Contact Info

Product

Resources

About

Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors