Fig 1.
The qualitative analysis for KBv cells cellular uptake.
Celluar uptake studies in KBv cells after 1 h treatment with (A) PF-DP and (C) c(RGDyK)-FP-DP or 1 h pre-incubation with 0.3 μg/mL of free c(RGDyK) peptide and then exposure to (B) PF-DP and (D) c(RGDyK)-FP-DP. Cells were examined by fluorescent microscopy; Red: DOX; Bar: 30 μm.
Fig 2.
Biodistribution studies in tumor bearing mice.
(A) In vivo fluorescence imaging of subcutaneous KBv tumor-bearing BALB/c nude mice after i.v. injection of PF/DIR and c(RGDyK)-FP/DIR at different time points; (B) Images of dissected organs of tumor bearing mice sacrificed at 48 h after i.v. injection of PF/DIR and c(RGDyK)-FP/DIR; The AUC0→48h of (C) DOX and (D) PTX in plasma and tissues after i.v. administration of the physical mixture of DOX and PTX (DOX+PTX), PF-DP and c(RGDyK)-FP-DP to subcutaneous KBv tumor-bearing BALB/c nude mice at a single 5 mg/kg dose of total drug, respectively. *P< 0.05, **P< 0.01, compared with DOX+PTX; #P< 0.05, ##P< 0.01, compared with PF-DP. Mean ± standard deviation (n = 3).
Fig 3.
The in vivo DOX concentration of free DOX and PTX mixture (DOX+PTX), PF-DP and c(RGDyK)-FP-DP in plasma and different tissues at specific time points following i.v. administration to KBv tumor-bearing mice at a single 5 mg/kg dose.
(A) Plasma; (B) Heart; (C) Liver; (D) Spleen; (E) Lung; (F) Kidney; (G) Tumor. Mean ± standard deviation (n = 3).
Fig 4.
The in vivo PTX concentration of free DOX and PTX mixture (DOX+PTX), PF-DP and c(RGDyK)-FP-DP in plasma and different tissues at specific time points following i.v. administration to KBv tumor-bearing mice at a single 5 mg/kg dose.
(A) Plasma; (B) Heart; (C) Liver; (D) Spleen; (E) Lung; (F) Kidney; (G) Tumor. Mean ± standard deviation (n = 3).
Fig 5.
In vivo anti-tumor efficacy of c(RGDyK)-FP-DP in subcutaneous KBv tumor-bearing mice.
(A) Changes in the tumor volume after treatments. Mean ± standard deviation (n = 6); (B) Kaplan-Meier survival curves of KBv tumor-bearing mice treated with different DOX+PTX, PF-DP and c(RGDyK)-FP-DP (10 mg/kg total drug for each dosing). Mean ± standard deviation (n = 8).
Table 1.
In vivo efficacy of various formulations on the survival of KBv tumor-bearing mice.
Fig 6.
Fluorescence images of tumor sections from KBv tumor-bearing BALB/c nude mice after various systemic administration.
(A, B, C) DOX+PTX; (D, E, F) PF-DP; (G, H, I) c(RGDyK)-FP-DP; Red: DOX; Blue: Hoechst 33258. Original magnification: ×20.
Fig 7.
Hematoxylin and eosin (H&E) stained tumor sections isolated from mice on 14th day after various different treatments.
Notes: (A) Saline, (B) DOX+PTX, (C) PF-DP and (D) c(RGDyK)-FP-DP. Original magnification: ×20.
Table 2.
The change in the body weight and tumor weight after different treatments in KBv tumor-bearing mice.
Table 3.
The hematological results in mice after different treatments.
Fig 8.
Hematoxylin and eosin (H&E) stained cardiac sections isolated from mice at 24 hours after the last intravenous dosing of different treatments.
(A) Saline, (B) DOX+PTX, (C) PF-DP and (D) c(RGDyK)-FP-DP. Original magnification: ×20.
Fig 9.
Fluorescence images of cardiac sections from KBv tumor-bearing BALB/c nude mice after systemic administration of different treatments.
(A, B, C) DOX+PTX, (D, E, F), PF-DP or (G, H, I) c(RGDyK)-FP-DP. Red: DOX; Blue: Hoechst 33258. Original magnification: ×20.