Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.
Amphiphilic acrylic copolymers with
hexamethyleneamine and poly(ethylene glycol) side chains can show
>100-fold selectivity toward Escherichia coli over
red blood cells. Homopolymer with cationic pendant amine groups is
highly hemolytic and antibacterial. Incorporation of approximately
33 mol % of poly(ethylene glycol) methyl ether methacrylate (PEGMA)
led to 1300 times reduction in hemolytic activity, while maintaining
high levels of antibacterial activity. The hemolytic activity of these
PEGylated copolymers depends on the overall content and spatial distribution
of the PEGMA units. Higher activity against Escherichia coli than Staphylococcus aureus was observed for this
polymer system, likely due to hydrogen bonding ability of the PEG
side chains with polysaccharide cell wall of the bacteria. Field emission
scanning electron microscopy analysis confirmed the bacterial membrane
rupture activity exerted by these copolymers, whereas time-kill studies
revealed significantly different bactericidal kinetics toward the
Gram-negative Escherichia coli and the Gram-positive Staphylococcus aureus.
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