An essential relationship between ATP depletion and chemosensitizing activity of Pluronic® block copolymers

Kabanov, Alexander V.; Batrakova, Elena V.; Alakhov, Valery

doi:10.1016/s0168-3659(03)00211-6

Cited by 124 publications

(82 citation statements)

References 29 publications

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“…It has been proposed that nonionic surfactants inhibit/modulate P-gp by various mechanisms, including changing membrane fluidity, inhibiting P-gp ATPase activity, and depleting ATP stores. [36][37][38][39][40] Interestingly, as we have previously demonstrated, if PCL5 is not maintained above an inhibitory concentration, PTX rapidly effluxes from the MDCKII-MDR1 cells, resulting in reduced inhibition of cell proliferation. 20 An additional experiment was conducted to determine the IC 50 of PTX-loaded nanospheres or micelles in the presence of PCL5 at its most effective concentration (0.05%).…”

Section: Cytotoxicity Of Ptx-loaded Nanoparticlesmentioning

confidence: 67%

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

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Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically "frozen core" structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin-Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells.

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Section: Cytotoxicity Of Ptx-loaded Nanoparticlesmentioning

confidence: 67%

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

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“…For example, Pluronic sensitizes MDR tumors by inhibiting the P-gp drug efflux system through ATP depletion (19,20). Tocopheryl polyethylene glycol succinate (TPGS), a water-soluble succinate ester of vitamin E, can inhibit P-gp-mediated drug efflux and increase the oral bioavailability of anticancer drugs (21).…”

Section: Introductionmentioning

confidence: 99%

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro

Tang

Ren

et al. 2016

Oncology Letters

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Abstract. Multidrug resistance (MDR) is a main clinical hurdle for chemotherapy of cancer, and overexpression of P-glycoprotein (P-gp) is a key factor. In the present study, a new co-delivery system for reversing MDR was designed and developed. The system was composed of curcumin (Cur) and piperine (Pip) encapsulated in solid lipid nanoparticles (SLNs) with tocopheryl polyethylene glycol succinate (TPGS) and Brij 78 [(Cur+Pip)-SLNs]. TPGS and Brij 78 could sensitize MDR tumors by inhibiting the P-gp drug efflux system. The combination of Cur and Pip, when administered in SLNs formulations, resulted in a significant enhancement in cytotoxicity and allowed efficient intracellular delivery of the drugs in drug-resistant A2780/Taxol cells. This dual inhibitory strategy may have significant potential in the clinical management of MDR in cancer.

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“…The depletion of ATP from cells proved to be a crucial method of killing cancer cells, as ATP is a key cellular metabolite. Several studies have found that ATP-depleting agents significantly enhanced the anticancer activity of chemotherapeutic reagents, and that ATP-depleting peptides or polymers are effective against drug-resistant cancer cells (39)(40)(41). Second, expressed streptolysin O damages the plasma membrane directly, and thus, the antiapoptotic machinery developed during cancer cell evolution is unable to inhibit streptolysin O-induced cancer cell death.…”

Section: Discussionmentioning

confidence: 99%

Suicide cancer gene therapy using pore-forming toxin, streptolysin O

Yang

Park

Yoon

et al. 2006

Molecular Cancer Therapeutics

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We cloned the streptolysin O gene from the Streptococcus pyogenes genome and tested the possibility of using it as an anticancer reagent. Transient transfection of the streptolysin O gene efficiently killed 293T cells after 12 hours of transfection as determined by lactate dehydrogenase release and propidium iodide uptake. No caspase activity was observed and necrosis was prominent during streptolysin O-induced cell death. Biochemical analysis of streptolysin O protein revealed that the deletion of only 5 amino acids from the COOH-terminal region of streptolysin O, which is essential for cholesterol binding activity, abolished its cell-killing activity, whereas the NH 2 -terminal region was more resilient, i.e., up to 115 amino acids could be deleted without changing its cell-killing activity. We generated a streptolysin O-expressing adenovirus and injected it into human cervical cancer cell -derived tumors grown in a nude mouse model. Twenty-one days postinjection, the average size of tumors in the streptolysin O adenovirus -injected group was 29.3% of that of the control PBS-treated group. Our results show that the genes of pore-forming toxins, like streptolysin O protein, have the potential to establish a novel class of suicide gene therapeutic reagents. [Mol Cancer Ther 2006;5(6):1610 -9]

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An essential relationship between ATP depletion and chemosensitizing activity of Pluronic® block copolymers

Cited by 124 publications

References 29 publications

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro

Suicide cancer gene therapy using pore-forming toxin, streptolysin O

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