Difunctional Pluronic copolymer micelles for paclitaxel delivery: Synergistic effect of folate-mediated targeting and Pluronic-mediated overcoming multidrug resistance in tumor cell lines

Wang, Yongzhong; Liu, Yu; Han, Limei; Sha, Xianyi; Fang, Xiaoling

doi:10.1016/j.ijpharm.2006.12.033

Cited by 210 publications

(117 citation statements)

References 22 publications

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“…F127-MTX, P105-FA, F127-FA, and P105-fluorescein isothiocyanate (FITC) were synthesized as described previously. 25,26 Propidium iodide (PI), chlorpromazine hydrochloride (CPZ), sucrose, filipin, genistein, cytochalasin D, 5-(N,N-dimethyl) amiloride hydrochloride (DMA), NaN 3 , monensin, and FA were purchased from Sigma (St Louis, MO, USA). Low-melting-point agarose was obtained from Yixin Biotechnology Co., Ltd. (Shanghai, People's Republic of China).…”

Section: Materials and Animalsmentioning

confidence: 99%

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

Chen¹,

Zhang²,

Huang³

et al. 2015

IJN

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The therapeutic effect of methotrexate (MTX)-conjugated Pluronic-based polymeric mixed micelles (F127/P105-MTX) on the folate receptor-overexpressing tumors treatment was investigated in this study. Due to its high structural similarity to folic acid and the high expression of folate receptor in most solid tumors, MTX serves as not only a cytotoxic agent but also a homing ligand. Cellular uptake and the endocytic mechanism studies of MTX-conjugated mixed micelles were performed in folate receptor-rich KBv and folate receptor-deficient A-549 cancer cells. Additionally, the efficacy and safety studies of F127/P105-MTX in KBv tumor-bearing mice were evaluated. Results indicate that F127/P105-MTX significantly enhanced the cellular uptake in KBv cells as compared to that of conventional non-MTX-conjugated mixed micelles. Moreover, the results showed that F127/P105-MTX can be internalized by both caveolae- and clathrin-mediated endocytosis in energy-dependent and folate receptor-dependent manners. The in vitro and in vivo antitumor efficacies of F127/P105-MTX were significantly enhanced in comparison with MTX-entrapped mixed micelles. Furthermore, no acute toxicities to hematological system and major organs have been observed after intravenous administration during the regimen. Therefore, our results suggest that F127/P105-MTX could be an effective and safe nano-drug delivery system for cancer therapy, especially for the folate receptor-rich cancer treatment.

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Section: Materials and Animalsmentioning

confidence: 99%

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

Chen¹,

Zhang²,

Huang³

et al. 2015

IJN

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“…12 Active targeting allows for the nanocarriers to selectively bind to receptors or antigens overexpressed on the surface of cancer cells and endocytosed by the cells. [13][14][15] In order to further increase the payload level inside the cancer cells, stimuli-triggered payload release was incorporated into the nanocarriers to achieve a controlled release pattern. Nanocarriers with triggered drug release mechanism in response to various physical or chemical stimuli such as high temperature, 16 pH 17 and ultrasound 18 have been developed to overcome the above-mentioned problem.…”

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

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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.

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“…As a member of the taxanes family, DTX was shown to be a P-gp substrate. 27 By ATP depletion, along with inhibition of the P-gp ATPase activity, Pluronic P105 has been demonstrated to inhibit the P-gp mediated efflux of the drug, 28,29 which might explain the hypersensitizing effect of Pluronic copolymers in the drug-resistant A549/Taxol cells. However, further studies are required to determine whether Pluronic copolymers increase the cell's uptake of DTX and to examine how Pluronic copolymers mediate the efflux of DTX in drug-resistant A549/Taxol cells.…”

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confidence: 99%

Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

Chen¹,

Sha²,

Jiang³

et al. 2013

IJN

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Abstract:The aim of this work was to establish a novel polymeric mixed micelle composed of Pluronic P105 and F127 copolymers loaded with the poorly soluble antitumor drug docetaxel (DTX) against Taxol-resistant non-small cell lung cancer. A central composite design was utilized to optimize the preparation process, helping to improve drug solubilization efficiency and micelle stability. Prepared by a thin-film hydration method, the average size of the optimized mixed micelle was 23 nm, with a 92.40% encapsulation ratio and a 1.81% drug-loading efficiency. The optimized formulation showed high storage stability in lyophilized form, with 95.7% of the drug content remaining after 6 months' storage at 4°C. The in vitro cytotoxicity assay showed that the IC50 values for Taxotere ® and mixed micelles were similar for A549, while on A549/Taxol cell lines, DTX-loaded P105/F127 mixed micelles showed a superior hypersensitizing effect; their IC50 value (0.059 µg/mL) was greatly reduced compared to those of Taxotere injections (0.593 µg/mL). The in vivo pharmacokinetic study showed that the mixed-micelle formulation achieved a 1.85-fold longer mean residence time in circulation and a 3.82-fold larger area under the plasma concentration-time curve than Taxotere. In addition, therapeutic improvement of mixed micelles in vivo against A549/Taxol was obtained. The tumor inhibition rate of the micelles was 69.05%, versus 34.43% for Taxotere (P , 0.01). Therefore, it could be concluded from the results that DTX-loaded P105/F127 mixed micelles might serve as a potential antitumor drug delivery system to overcome multidrug resistance in lung cancer.

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Difunctional Pluronic copolymer micelles for paclitaxel delivery: Synergistic effect of folate-mediated targeting and Pluronic-mediated overcoming multidrug resistance in tumor cell lines

Cited by 210 publications

References 22 publications

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

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

Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

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Difunctional Pluronic copolymer micelles for paclitaxel delivery: Synergistic effect of folate-mediated targeting and Pluronic-mediated overcoming multidrug resistance in tumor cell lines

Cited by 210 publications

References 22 publications

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on&nbsp;the folate receptor-rich tumors treatment

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on&nbsp;the folate receptor-rich tumors treatment

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

Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

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The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment

The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment