Methotrexate Loaded Polyether-Copolyester Dendrimers for the Treatment of Gliomas: Enhanced Efficacy and Intratumoral Transport Capability

Dhanikula, Renu Singh; Argaw, Anteneh; Bouchard, Jean‐François; Hildgen, Patrice

doi:10.1021/mp700086j

Cited by 227 publications

(132 citation statements)

References 45 publications

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“…Due to problems of solubility, the salt 4 could not be grafted on a phosphorus-containing dendrimer, but the neutral rhodamine derivative 3B was successfully grafted as terminal groups. A few papers have reported the synthesis of dendrimers labeled with rhodamine (rhodamine being linked to one or a few terminal functions 13,14 ) but to the best of our knowledge, 5-G 1 is the first example of a dendrimer bearing rhodamine moieties on all terminal groups. Addition of HCl did not damage the structure of the dendrimer, and does not open the spirolactam form of the rhodamine terminal groups (or only some of them).…”

Section: Discussionmentioning

confidence: 99%

Synthesis and characterization of phosphorus-containing dendrimers bearing rhodamine derivatives as terminal groups

Wei¹,

Laurent²,

Majoral³

et al. 2010

Arkivoc

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The synthesis of two new derivatives of Rhodamine B functionalized by phenols is reported. For one rhodamine derivative, the equilibrium between the open form and the ring-closed (spirolactam) form is completely shifted toward the latter, whereas the constitution of the other rhodamine derivative precludes ring closure. The spirolactam derivative was grafted as terminal group to a first generation phosphorus-containing dendrimer. Attempts to open the spirolactam form by adding HCl failed and resulted only in protonation of the NEt 2 substituent of rhodamine.

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Section: Discussionmentioning

confidence: 99%

Synthesis and characterization of phosphorus-containing dendrimers bearing rhodamine derivatives as terminal groups

Wei¹,

Laurent²,

Majoral³

et al. 2010

Arkivoc

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“…Using an in vitro BBB model, polyether-copolyester (PEPE) dendrimers have been shown to cross the BBB. Glycosylation of these dendrimers was found to further increase the permeation 65 . Interestingly, toxicity of uncharged and/or glycosylated dendrimers is lower than cationic dendrimers 38,[53][54][55] .…”

Section: Effect Of Maltose Modification On Anti-prion Activity Of Ppimentioning

confidence: 99%

Influence of Surface Functionality of Poly(propylene imine) Dendrimers on Protease Resistance and Propagation of the Scrapie Prion Protein

et al. 2010

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Accumulation of PrPSc , an insoluble and protease-resistant pathogenic isoform of the cellular prion protein (PrP C ) is a hallmark in prion diseases. Branched polyamines, including PPI (poly(propylene imine)) dendrimers are able to remove protease resistant PrP Sc and abolish infectivity, offering possible applications for therapy. These dendrimer types are thought to act through their positively charged amino surface groups. In the present study the molecular basis of the anti-prion activity of dendrimers was further investigated employing modified PPI dendrimers, in which the positively charged amino surface groups were substituted with neutral carbohydrate units of maltose (mPPI) or maltotriose (m3PPI). Modification of surface groups greatly reduced the toxicity associated with unmodified PPI, but did not abolish its anti-prion activity, suggesting that the presence of cationic surface groups is not essential for dendrimer action. PPI and mPPI dendrimer of generation 5 were equally effective in reducing levels of protease-resistant PrP Sc (PrP res ) in a dose-and time-dependent manner in ScN2a cells, and in preexisting aggregates in homogenates from infected brain. Solubility assays revealed that total levels of PrP Sc in scrapie infected mouse neuroblastoma (ScN2a) cells were reduced by mPPI. Coupled with the known ability of polyamino dendrimers to render protease-resistant PrP Sc in pre-existing aggregates of PrP Sc susceptible to proteolysis, these findings strongly suggest that within infected cells dendrimers reduce total amounts of PrP Sc by mediating its denaturation and subsequent elimination.

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“…Spheroid cultures were prepared using a protocol adapted from the previously established liquid overlay system: confluent U251N monolayer cell cultures were detached using 0.05% trypsin-EDTA (Invitrogen, Canada), and seeded at 5,000 cells per well in 96-well plates pre-coated with 2% agarose (Invitrogen, Canada) in serum-deprived DMEM [44]. Spheroids were seeded and maintained in complete DMEM medium for four days before drug treatments.…”

Section: Spheroid Preparationmentioning

confidence: 99%

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Zhang

Cui

Amiri

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tIncreased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme.

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Methotrexate Loaded Polyether-Copolyester Dendrimers for the Treatment of Gliomas: Enhanced Efficacy and Intratumoral Transport Capability

Cited by 227 publications

References 45 publications

Synthesis and characterization of phosphorus-containing dendrimers bearing rhodamine derivatives as terminal groups

Synthesis and characterization of phosphorus-containing dendrimers bearing rhodamine derivatives as terminal groups

Influence of Surface Functionality of Poly(propylene imine) Dendrimers on Protease Resistance and Propagation of the Scrapie Prion Protein

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

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