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Original Research

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system

, , , , , , , , , & show all
Pages 4535-4547 | Published online: 16 Jul 2015

Figures & data

Figure 1 Characterization of NIR797-labeled NPs.

Notes: (A) Transmission electron microscopic images, (B) particle size distribution, (C) schematic diagram, (D) fluorescence intensity.

Abbreviations: Tf, transferrin; PEG, polyethylene glycol; PLL, poly-l-lysine; PLGA, poly(lactic-co-glycolic acid); NIR, near-infrared; DNR, daunorubicin; NPs, nanoparticles; SSC-H, side scatter light histogram; FL3-H, fluorescent light 3 histogram.

Figure 1 Characterization of NIR797-labeled NPs.Notes: (A) Transmission electron microscopic images, (B) particle size distribution, (C) schematic diagram, (D) fluorescence intensity.Abbreviations: Tf, transferrin; PEG, polyethylene glycol; PLL, poly-l-lysine; PLGA, poly(lactic-co-glycolic acid); NIR, near-infrared; DNR, daunorubicin; NPs, nanoparticles; SSC-H, side scatter light histogram; FL3-H, fluorescent light 3 histogram.

Figure 2 Photographs showing the appearance of tumor body in tumor-bearing nude mice (A) and tumor size (B) at the end of treatment, relative tumor volume (C), and tumor inhibition rate (D) after the treatment.

Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs.

Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin; d, day.

Figure 2 Photographs showing the appearance of tumor body in tumor-bearing nude mice (A) and tumor size (B) at the end of treatment, relative tumor volume (C), and tumor inhibition rate (D) after the treatment.Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs.Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin; d, day.

Figure 3 Histopathological examination of organs and tumor tissues in K562/A02 xenograft model after the treatment (hematoxylin–eosin staining, ×200).

Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs.

Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin.

Figure 3 Histopathological examination of organs and tumor tissues in K562/A02 xenograft model after the treatment (hematoxylin–eosin staining, ×200).Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs.Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin.

Figure 4 Expression of Bax, caspase-3, Bcl-2, and survivin in tumor tissues after the treatment (immunohistochemistry, ×400).

Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs.

Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin.

Figure 4 Expression of Bax, caspase-3, Bcl-2, and survivin in tumor tissues after the treatment (immunohistochemistry, ×400).Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs.Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin.

Figure 5 Expression of TfR, P-gp, MRP, NF-κB mRNAs (A) and proteins (B, C) after the treatment.

Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs. *P<0.05 when compared to DNR-Tet-NPs.

Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin; P-gp, P-glycoprotein; MRP, multidrug resistance protein; NF-κB, nuclear factor kappaB; TfR, Tf receptor; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Figure 5 Expression of TfR, P-gp, MRP, NF-κB mRNAs (A) and proteins (B, C) after the treatment.Notes: (a) Control, (b) DNR, (c) DNR and Tet, (d) DNR-NPs, (e) DNR-Tet-NPs, (f) DNR-Tet-Tf-NPs. *P<0.05 when compared to DNR-Tet-NPs.Abbreviations: DNR, daunorubicin; Tet, tetrandrine; NPs, nanoparticles; Tf, transferrin; P-gp, P-glycoprotein; MRP, multidrug resistance protein; NF-κB, nuclear factor kappaB; TfR, Tf receptor; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Figure 6 The apoptosis assay on K562 cells after the treatment with NIR797-labeled NPs.

Note: *P<0.05 when compared to control group.

Abbreviations: SSC-H, side scatter light histogram; FL1-H, fluorescent light 1 histogram; AV, annexin V-FITC; DNR, daunorubicin; NPs, nanoparticles; Tf, transferrin; NIR, near-infrared.

Figure 6 The apoptosis assay on K562 cells after the treatment with NIR797-labeled NPs.Note: *P<0.05 when compared to control group.Abbreviations: SSC-H, side scatter light histogram; FL1-H, fluorescent light 1 histogram; AV, annexin V-FITC; DNR, daunorubicin; NPs, nanoparticles; Tf, transferrin; NIR, near-infrared.

Figure 7 K562 cells observed by digital confocal microscope.

Note: The blue arrow demonstrates drug-loaded NPs were endocytosed in necrosis and apoptotic cells.

Abbreviations: NIR, near-infrared; DNR, daunorubicin; Tf, transferrin; NPs, nanoparticles.

Figure 7 K562 cells observed by digital confocal microscope.Note: The blue arrow demonstrates drug-loaded NPs were endocytosed in necrosis and apoptotic cells.Abbreviations: NIR, near-infrared; DNR, daunorubicin; Tf, transferrin; NPs, nanoparticles.

Figure 8 NIRF images of K562 cells in vitro (A) and in tumor-bearing mice (B) after the treatment.

Notes: (a) NIR797-labeled DNR-NPs, (b) NIR797-labeled DNR-Tf-NPs. The blue arrow shows the DNR concentration in tumor tissue.

Abbreviations: NIRF, near-infrared fluorescence; DNR, daunorubicin; NPs, nanoparticles; Min, minimum; Max, maximum; h, hour; Tf, transferrin.

Figure 8 NIRF images of K562 cells in vitro (A) and in tumor-bearing mice (B) after the treatment.Notes: (a) NIR797-labeled DNR-NPs, (b) NIR797-labeled DNR-Tf-NPs. The blue arrow shows the DNR concentration in tumor tissue.Abbreviations: NIRF, near-infrared fluorescence; DNR, daunorubicin; NPs, nanoparticles; Min, minimum; Max, maximum; h, hour; Tf, transferrin.