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Original Articles

Octa-arginine modified poly(amidoamine) dendrimers for improved delivery and cytotoxic effect of paclitaxel in cancer

, ORCID Icon, ORCID Icon &
Pages 847-859 | Received 03 Apr 2018, Accepted 23 Apr 2018, Published online: 23 May 2018

Figures & data

Figure 1. Schematic representation of the synthesis of multifunctional G4 dendrimer conjugate.

Figure 1. Schematic representation of the synthesis of multifunctional G4 dendrimer conjugate.

Figure 2. 1H NMR spectrum of (A) G4-PTX-PEG and (B) G4-PTX-PEG-R8 in D2O at 300 MHz.

Figure 2. 1H NMR spectrum of (A) G4-PTX-PEG and (B) G4-PTX-PEG-R8 in D2O at 300 MHz.

Table 1. Zeta potential values of multifunctional dendrimer conjugates (mean ± SD, n = 3).

Figure 3. Percentage of hemolysis obtained from the interaction of the G4 conjugates with RBC suspension. Data is represented as mean ± SD, n = 3. Statistical significance was determined for G4 PEG and G4 PEG R8 against plain G4 dendrimer.

Figure 3. Percentage of hemolysis obtained from the interaction of the G4 conjugates with RBC suspension. Data is represented as mean ± SD, n = 3. Statistical significance was determined for G4 PEG and G4 PEG R8 against plain G4 dendrimer.

Figure 4. (A) Confocal microscopy images of HeLa cells after 1 and 4 h of incubation with F-G4-PEG and F-G4-PEG-R8. (B) Cellular uptake of fluorescently tagged G4 conjugates with and without R8 modification in HeLa cells after 1 and 4 h incubation as assessed by flow cytometer (mean ± SD, n = 3).

Figure 4. (A) Confocal microscopy images of HeLa cells after 1 and 4 h of incubation with F-G4-PEG and F-G4-PEG-R8. (B) Cellular uptake of fluorescently tagged G4 conjugates with and without R8 modification in HeLa cells after 1 and 4 h incubation as assessed by flow cytometer (mean ± SD, n = 3).

Figure 5. Percentage cell viability of HeLa cells treated with different concentrations of PTX, G4-PTX-PEG and G4-PTX-PEG-R8 at 24 and 48 h (mean ± SD; n = 3).

Figure 5. Percentage cell viability of HeLa cells treated with different concentrations of PTX, G4-PTX-PEG and G4-PTX-PEG-R8 at 24 and 48 h (mean ± SD; n = 3).

Figure 6. Quantitative estimation of apoptosis induced by various PTX treatments as studied by AnnexinV FITC/PI staining assay. Q1: live cells; Q2: early apoptotic; Q3: late apoptotic; Q4: necrotic cells.

Figure 6. Quantitative estimation of apoptosis induced by various PTX treatments as studied by AnnexinV FITC/PI staining assay. Q1: live cells; Q2: early apoptotic; Q3: late apoptotic; Q4: necrotic cells.

Figure 7. (A) Penetration of G4 conjugates in 3D cultured spheroids at various depths after 1 and 4 h incubation captured as Z-stacks by confocal microscopy. (B) Quantitative assessment of cellular uptake in 3D spheroids treated with F-G4-PEG and F-G4-PEG-R8 by flow cytometry (mean ± SD; n = 3).

Figure 7. (A) Penetration of G4 conjugates in 3D cultured spheroids at various depths after 1 and 4 h incubation captured as Z-stacks by confocal microscopy. (B) Quantitative assessment of cellular uptake in 3D spheroids treated with F-G4-PEG and F-G4-PEG-R8 by flow cytometry (mean ± SD; n = 3).

Figure 8. (A) Photomicrograph of spheroids after different PTX treatments captured at Day 0, Day 3 and Day 6 using bright field microscope at 10× magnification. (B) Graphical representation of spheroid growth inhibition (mean of diameter in µm ± SD; n = 3).

Figure 8. (A) Photomicrograph of spheroids after different PTX treatments captured at Day 0, Day 3 and Day 6 using bright field microscope at 10× magnification. (B) Graphical representation of spheroid growth inhibition (mean of diameter in µm ± SD; n = 3).

Figure 9. In vitro cytotoxicity induced by PTX, G4-PTX-PEG and G4-PTX-PEG-R8 at 24 h in tumor spheroids as assessed by Presto blue assay (mean of percentage cell viability ± SD; n = 3).

Figure 9. In vitro cytotoxicity induced by PTX, G4-PTX-PEG and G4-PTX-PEG-R8 at 24 h in tumor spheroids as assessed by Presto blue assay (mean of percentage cell viability ± SD; n = 3).

Figure 10. Live/dead cell micrographs of tumor spheroids captured using fluorescence microscope at 10× magnification.

Figure 10. Live/dead cell micrographs of tumor spheroids captured using fluorescence microscope at 10× magnification.
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