Figures & data
Table 1 Physicochemical properties of different formulations (n = 3)
Figure 1 Schematic diagram showing the structure of lipid/polymer particle assemblies. The negative phosphate charges on the hydrophilic segment of DPPC (green) can be attracted to the oppositely charged ions of the ammonium bromide ammonia headgroup of DMAB (blue), which modify the surface of DOX-loaded PLGA nanoparticles (red).
Abbreviations: DMAB, dimethyldidodecylammonium bromide; DOX, doxorubicin; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; LNP, lipid/polymer particle assembly; PLGA, poly(lactic-co-glycolic) acid.
Figure 2 TEM and SEM images of LNPs formed with a core-shell supramolecular structure. A TEM image shows relatively uniform sized LNP particles (A), and a LipoParticle revealing its lipid shell thickness (B). A SEM image shows the fairly rigid surface morphology of PLGA particles by the electron-beam bombardment effect (C), and another SEM image displays the degradation and cracking of LNPs with a DPPC shell (D).
Abbreviations: DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; LNPs, lipid/polymer particle assemblies; SEM, scanning electron microscopy; TEM, transmission electron microscopy.
Figure 3 In vitro drug release profiles of DOX-loaded LNPs at different pH (5.5, 6.5, and 7.4) and 37°C.
Abbreviations: DOX, doxorubicin; LNPs, lipid/polymer particle assemblies.
Figure 4 P-gp expression in MCF-7 and MCF-7/ADR cells, as shown by flow cytometry analysis.
Note: **P < 0.01.
Abbreviations: MCF-7, Michigan Cancer Foundation-7; MCF-7/ADR, MCF-7/adriamycin; P-gp, P-glycoprotein.
Figure 5 Confocal images of the intracellular accumulation of free DOX and LNPs- DOX in MCF-7 (A) and MCF-7/ADR (B) cells. Cells were treated with 8 μg/mL free DOX or an equivalent concentration of LNPs-DOX for the different time periods as indicated. Nuclear (blue) uptake of DOX was increased dramatically by LNPs.
Abbreviations: DOX, doxorubicin; free DOX, free doxorubicin; LNPs-DOX, doxorubicin loaded in lipid/polymer particle assemblies; MCF-7, Michigan Cancer Foundation-7; MCF-7/ADR, MCF-7/adriamycin.
Figure 6 Accumulation of free DOX or LNPs-DOX in MCF-7 and MCF-7/ADR cells. Cells were treated with 8 μg/mL DOX or an equivalent concentration of LNPs-DOX for 15 minutes and 1 hour. The intracellular DOX was then determined by flow cytometry analysis.
Notes: *P < 0.05; **P < 0.01; ***P < 0.001.
Abbreviations: DOX, doxorubicin; free DOX, free doxorubicin; h, hours; LNPs- DOX, doxorubicin loaded in lipid/polymer particle assemblies; MCF-7, Michigan Cancer Foundation-7; MCF-7/ADR, MCF-7/adriamycin; NS, no significance.
Figure 7 IC50 for free DOX or LNPs-DOX in MCF-7 and MCF-7/ADR cells. Cells were treated with various concentrations of DOX or LNPs-DOX at the same dose for 24 hours.
Note: ***P < 0.001.
Abbreviations: Free DOX, free doxorubicin; IC50, half maximal inhibitory concentration; h, hours; LNPs-DOX, doxorubicin loaded in lipid/polymer particle assemblies; MCF-7, Michigan Cancer Foundation-7; MCF-7/ADR, MCF-7/adriamycin; NS, no significance.
Figure S1 Gel Permeation chromatogram of DOX-PLGA conjugate (solid line) and unconjugated PLGA (dotted line)
Abbreviations: DOX, doxorubicin; PLGA, poly(lactic-co-glycolic) acid.
Figure S2 In vitro drug release profiles of DOX-loaded PLGA nanoparticles (without DPPC shell) in different pH (5.5, 6.5, and 7.4) at 37°C. Error bars indicate mean ± SD.
Abbreviations: DOX, doxorubicin; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; PLGA, poly(lactic-co-glycolic) acid; SD, standard deviation.
Figure S3 Cytotoxicity of Free-DOX against MCF-7 and MCF-7/ADR cells. Error bars indicate mean ± SD.
Abbreviations: DOX, doxorubicin; MCF-7, Michigan Cancer Foundation-7; MCF-7/ADR, MCF-7/adriamycin; SD, standard deviation.
