Dendrimer Nanodevices and Gallic Acid: Comparison
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Please note this is a comparison between Version 4 by Silvana Alfei and Version 11 by Catherine Yang.

Human neuroblastoma (NB), a pediatric tumor inclined to relapse, after an initial response to therapy, usually develops resistance. Since several chemotherapeutics, including the weel known etoposide (ETO), exert anticancer effect by increasing reactive oxygen species (ROS), NB cells overproduce antioxidant compounds becoming drugs-resistant. Moreover, ETO, although widely used, suffers from fast metabolism, poor solubility and systemic toxicity, that limit its administration dosage and its therapeutic efficiency. An appealing strategy to sensitize NB cells to chemotherapy involves the use of less toxic natural compounds able to reduce antioxidant defenses of NB cells and to induce ROS overproduction. In this contest, although affected by several issues as instability and poor absorbability, antioxidant/pro-oxidant polyphenols, such as gallic acid (GA), showed pro-oxidant anti-cancer effects and low toxicity for healthy cells, in several kind of tumors, not including NB. Herein, for the first time, free GA, two GA-dendrimers, and the dendrimer adopted as GA reservoir were tested on both sensitive and chemoresistant NB cells. Furthermore, the dendrimer adopted as carrier for GA was exploited also for entrapping and protecting ETO and for enhancing its solubility and effectiveness.The dendrimer device induced ROS-mediated death both in sensitive NB cellsalso and also in chemoresistant ones. Free GA proved a dose-dependent ROS-mediated cytotoxicity on both cell populations. Intriguingly, when administered in dendrimer formulations at a dose not cytotoxic for NB cells, GA nullified any pro-oxidant activity of dendrimer. Unfortunately, due to GA, nanoformulations were inactive on NB cells, but GA resized in nanoparticles showed considerable ability in counteracting, at low dose, ROS production and oxidative stress, herein induced by the dendrimer. Interestingly, the ETO-dendrimer showed a synergistic action, controlled of ETO with dendrimer, slowly released the drug over time with aand significantly improved drugits bioactivity, representing a novel biodegradable and promising device for the delivery of ETO into NB cells.

  • Human neuroblastoma
  • gallic acid (GA)
  • polyester dendrimers
  • dendrimer nanoformulations
  • etoposide (ETO)
  • ETO loaded dendrimer
  • ROS-mediated anticancer effect
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