Folic acid-conjugated amphiphilic alternating copolymer as a new active tumor targeting drug delivery platform

Figures & data

Figure 1 (A) Chemical structure of SMA; (B) SMA self-assembly at pH 7 in aqueous solution.

Abbreviation: SMA, poly(styrene-alt-maleic anhydride).

Figure 2 Molecular modeling and transmission electron microscopy characterization of the self-assembled structure of SMA at (A) low molecular weight and (B) high molecular weight. Adapted with permission of Taylor & Francis, from Molecular Simulation, Characterization of a novel self-association of an alternating copolymer into nanotubes in solution, Malardier-Jugroot C, van de Ven TGM, Whitehead MA, 31, 2–1, 2005; permission conveyed through Copyright Clearance Center, Inc.,⁴⁵ and adapted from Chemical Physics Letters, 636, McTaggart M, Malardier-Jugroot C, Jugroot M, Self-assembled biomimetic nanoreactors I: polymeric template, 206–220, Copyright (2015), with permission from Elsevier.⁴⁶

Abbreviation: SMA, poly(styrene-alt-maleic anhydride).

Figure 3 FA-DABA-PSMA oligomer at pH 7 at #1 carboxylic acid using ONIOM model: central trimer optimized to DFT, outer two to PM6. Adapted with permission from Biophy Chem, 214–215, Li X, McTaggart M, Malardier-Jugroot C, Synthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery system, 17–26. Copyright (2016), with permission from Elsevier.¹⁶

Abbreviations: DFT, density functional theory; PM6, complete parameter optimization.

Figure 4 Schematic representation of FA-DABA-SMA in its “off” state and “on” state.

Notes: Yellow spheres represent folic acid molecules, green represents hydrophobic drugs, blue shows the hydrophilic part of the polymers, and finally, the gray is the hydrophobic part of the polymer. Adapted with permission from Biophy Chem, 214–215, Li X, McTaggart M, Malardier-Jugroot C, Synthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery system, 17–26. Copyright (2016), with permission from Elsevier.¹⁶

Figure 5 Dynamic light scattering results of (A) pure 0.05 wt% SMA solution and (B) 1 wt% PSMA-DABA-FA with mean zeta potential of −39.89 mV.

Notes: The presented line in the graph is a guide for the eyes. Adapted with permission from Biophy Chem, 214–215, Li X, McTaggart M, Malardier-Jugroot C, Synthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery system, 17–26. Copyright (2016), with permission from Elsevier.¹⁶
Abbreviations: DABA, biodegradable linker 2,4-diaminobutyric acid; FA, folic acid; SMA, poly(styrene-alt-maleic anhydride).

Figure 6 Chemical structure of curcumin and fluorescence intensity of curcumin in water and when encapsulated in SMA polymers (PSMA) (1% wt to water) at excitation wavelength 420 nm.

Abbreviation: SMA, poly(styrene-alt-maleic anhydride).

Figure 7 Fluorescent images showing cellular uptake of curcumin-loaded SMA in (A) RAW-Blue and (B) PANC-1 cell lines.

Notes: Images in the left column indicate (A) RAW-Blue cell line with concentrations of (a) 0.3, (b) 1, (c) 3, and (d) 10 μm of curcumin-loaded SMA, respectively, and images in the right column indicate (B) PANC-1 cell line with concentrations of (a) 0.3, (b) 1, (c) 3, and (d) 10 μm of curcumin-loaded SMA, respectively. The image bar scale represents 100 μm.
Abbreviations: SMA, poly(styrene-alt-maleic anhydride); Cur, curcumin.

Figure 8 Fluorescent images showing cellular uptake of curcumin-loaded FA-DABA-SMA in (A) RAW-Blue and (B) PANC-1 cell lines.

Notes: Images in the left column indicate (A) RAW-Blue cell line with concentrations of (a) 0.3, (b) 1, (c) 3, and (d) 10 μm of curcumin-loaded FA-DABA-SMA, respectively, and images in the right column indicate (B) PANC-1 cell line with concentrations of (a) 0.3, (b) 1, (c) 3, and (d) 10 μm of curcumin-loaded FA-DABA-SMA, respectively. The image bar scale represents 100 μm.
Abbreviations: SMA, poly(styrene-alt-maleic anhydride); Cur, curcumin.

Figure 9 Viability of PANC-1 cells treated with empty SMA at different doses using the WST-1 assay.

Notes: The control is represented by the cells alone. Indicated P-values vs untreated cells alone (n=5).
Abbreviations: SMA, poly(styrene-alt-maleic anhydride); SEM, standard error of mean.

Figure 10 Viability of PANC-1 cells treated with empty FA-DABA-SMA at different doses using the WST-1 assay.

Notes: The control is represented by the cells alone. Indicated P-values vs untreated cells alone (n=5).
Abbreviations: SMA, poly(styrene-alt-maleic anhydride); SEM, standard error of mean.

Figure 11 Viability of PANC-1 cells treated with Cur-encapsulated FA-DABA-SMA at different doses using the WST-1 assay.

Notes: The control is represented by the cells alone. Indicated P-values vs untreated cells alone (n=5).
Abbreviations: SMA, poly(styrene-alt-maleic anhydride); Cur, curcumin; SEM, standard error of mean.

Figure 12 Comparison of viability of PANC-1 cells at 72 hours treated with SMA, FA-DABA-SMA, and Cur-encapsulated FA-DABA-SMA at different doses using the WST-1 assay (n=5).

Abbreviations: SMA, poly(styrene-alt-maleic anhydride); Cur, curcumin; SEM, standard error of mean.

Malardier-JugrootCvan de VenTGMWhiteheadMACharacterization of a novel self-association of an alternating copolymer into nanotubes in solutionMol Simul2005312–1173178

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McTaggartMMalardier-JugrootCJugrootMSelf-assembled biomimetic nanoreactors I: polymeric templateChem Phys Lett2015636216220

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LiXMcTaggartMMalardier-JugrootCSynthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery systemBiophy Chem2016214–2151726

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