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International Journal of Nanomedicine Volume 10, 2015 - Issue
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Original Research

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

Liting Guo1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China
,
Haijun Zhang1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China
,
Fei Wang1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China
,
Ping Liu1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China
,
Yonglu Wang1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China;2 School of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China
,
Guohua Xia1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China
,
Ran Liu1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China
,
Xueming Li2 School of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China
,
Haixiang Yin2 School of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China
,
Hulin Jiang3 Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China
&
Baoan Chen1 Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of ChinaCorrespondence[email protected]
 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.

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