Nanomicellar paclitaxel increases cytotoxicity of multidrug resistant breast cancer cells

Nanomicellar paclitaxel increases cytotoxicity of multidrug resistant breast cancer cells,10.1016/j.canlet.2008.09.041,Cancer Letters,Hayat Önyüksel,E

Nanomicellar paclitaxel increases cytotoxicity of multidrug resistant breast cancer cells   (Citations: 3)
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Multidrug resistance (MDR) of breast cancer cells still represents an unmet medical need in chemotherapy. To this end, the purpose of this study was to determine efficacy of paclitaxel loaded in sterically stabilized, biocompatible and biodegradable sterically stabilized mixed phospholipid nanomicelles (SSMM; size, ∼15nm) and actively targeted vasoactive intestinal peptide-grafted SSMM (SSMM-VIP) in circumventing P-gp-mediated paclitaxel resistance in BC19/3 cells, a human breast cancer cell line that expresses >10-fold higher P-gp than its parental sensitive cell line, MCF-7. We found that in drug sensitive MCF-7 cells, paclitaxel loaded in SSMM (P-SSMM) and SSMM-VIP (P-SSMM-VIP) significantly inhibited cell growth in dose-dependent fashion (p<0.05). Both formulations were ∼7-fold more potent than paclitaxel dissolved in DMSO (P-DMSO). Efficacy of P-SSMM and P-SSMM-VIP was similar (p>0.5). By contrast, in drug resistant BC19/3 cells, P-SSMM-VIP was significantly more effective than either P-SSMM or P-DMSO (∼2- and 5-fold, respectively; p<0.05). Collectively, these data indicate that actively targeted paclitaxel-loaded SSMM-VIP overcomes multiple drug resistance of BC19/3 cells. We suggest this formulation should be further developed to treat MDR breast cancer.
Journal: Cancer Letters - CANCER LETT , vol. 274, no. 2, pp. 327-330, 2009
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    • ...Formulation strategies like biodegradable polymer-based nanoparticles (11,12), polymeric-micelles (13) and polymerdrug conjugates (14) have been investigated to overcome P-gp-mediated drug resistance...
    • ...This might be partially related to phagocytosis of the nanoparticles by the cancer cells during rapid cell proliferation (13)...
    • ...Some researchers (13) hypothesized that paclitaxelloaded nanoparticles may alter the composition and fluidity of the cell membrane, thereby altering the activity of P-gp, or activating the intracellular signal transduction mechanism(s) to down-regulate P-gp expression...

    Fei Renet al. Paclitaxel-Loaded Poly(n-butylcyanoacrylate) Nanoparticle Delivery Sys...

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