Right panels show the mean intensity of the DiR fluorescent signals of tumor (Mean net intensity = Sum Intensity/Area, n=5). Representative images of tumors from each group ( n =5) are shown ( b, middle). On day 30 after tumor cells were injected, tumors were removed and imaged with a Kodak Image station. injection every three days for a total of ten injections. After tumor cells were injected, mice were treated with DiR dye labeled agents as listed in fig. into BALB/c mice (CT26, 1×10 6/mouse, left, top) or NOD-SCID mice (SW620, 5×10 6/mouse, left, bottom). One representative experiment of 2 independent experiments is shown ( n = 5) (* p<0.05) ( a, right, bottom). Surviving percent of GNVs-JSI-124-treated mice was compared to control mice. The results are based on two independent experiments with data pooled for mice in each experiment ( n = 5) and presented as the mean ± s.e.m. The growth potential of injected GL26-Luc cells was determined by dividing photon emissions of mice treated with PBS by the photon emissions of mice treated with GNVs, JSI-124, or GNVs-JSI-124 ( a, right, top). A representative photograph showing the brain tumor signals of a mouse from each group ( n = 5) ( a, left).

The mice were imaged on post-injection days as indicated in a. of at least three independent experiments.Ī, C57BL/6J mice were implanted with GL26-Luc cells, GNVs were loaded with Stat3 inhibitor JSI-124 and then intranasally administrated to mice. d, The biological effect of luciferase specific siRNA carried by GNVs or Lipofectamine 2000 on inhibition of luciferase activity of transfected GL26-luc and A549-luc cells was evaluated using a luciferase assay (n=3). The results indicate the activity of luciferase expressed in the transfected T cells (n=5). 24h later the expression of luciferase in CD4 and CD8 cells was detected. c, GNVs encapsulating psiCHECK2 were loaded with biotin labeled anti-CD4 or CD8 antibodies, and then incubated with mouse spleen CD4 + or CD8 + cells. Data (a, b) are representative of at least three independent experiments. b, PKH26-GNVs loaded with biotin labeled anti-CD4 or anti-CD8 antibodies were incubated in vitro with splenocytes, the PKH26 positive cells were qualitatively analyzed by FACS. YFP positive cells were quantitatively analyzed by FACS (right panel). A representative image of transfected cells is shown (left panel). Data (a, b, d, and e) are representative of at least three independent experiments.Ī, A549 cells were transfected with biotinylated eYFP carried by GNVs or Lipofectamine 2000. e, Size distribution of the GNVs before (left) and after (right) homogenization was further analyzed using a Zeta potential Analyzer. Original magnification was ×50000 (left) with enlargement of the indicated area shown in the right panel.

d, GNVs embedded in polyBed 812 were sectioned and examined by electromicroscopy.

The composition is reported in detail in Supplementary Table S1 in the Supporting Information. c, Pie chart with a summary of the putative lipid species in GNVs, reported as percent of total GNVs lipids.

Size distribution of the particles was further analyzed using a Zeta potential Analyzer (right). b, Sucrose banded grapefruit lipid derived GNVs indicated by the arrow (left) were examined using EM and photographed (middle). Size distribution of the particles was further analyzed by Zetasizer Nano ZS (right). Grapefruit-derived nanovectors are less toxic than nanoparticles made of synthetic lipids and, when injected intravenously into pregnant mice, do not pass the placental barrier, suggesting that they may be a useful tool for drug delivery.Ī, Sucrose banded particles from grapefruit juice (left) and EM visualization of nano sized particles (middle). The therapeutic potential of grapefruit-derived nanovectors was further demonstrated by enhancing the chemotherapeutic inhibition of tumour growth in two tumour animal models. We demonstrate the in vivo targeting specificity of grapefruit-derived nanovectors by co-delivering therapeutic agents with folic acid, which in turn leads to significantly increasing targeting efficiency to cells expressing folate receptors. Here we show that nanoparticles made of grapefruit-derived lipids, which we call grapefruit-derived nanovectors, can deliver chemotherapeutic agents, short interfering RNA, DNA expression vectors and proteins to different types of cells. Although the use of nanotechnology for the delivery of a wide range of medical treatments has potential to reduce adverse effects associated with drug therapy, tissue-specific delivery remains challenging.

Grapefruit method