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. 2009 Apr 21;4(4):e5233. doi: 10.1371/journal.pone.0005233

Figure 6. HPMA copolymer-ALN-TNP-470 conjugate reduces vascular hyperpermeability in mouse skin capillaries and inhibits MG-63-Ras human osteosarcoma growth.

Figure 6

(A) Diminished dye is observed in mice treated with free or conjugated ALN and TNP-470 compared to untreated control group. Scale bar represents 10 mm. (B) Extracted dye content quantification by measurement at 620 nm. (C) Intravital non-invasive fluorescence imaging of mCherry-labeled MG-63-Ras tumor-bearing mice treated with free or conjugated ALN and TNP-470. (D) Antitumor effect of free (open triangles) or conjugated (closed triangles) ALN and TNP-470 on MG-63-Ras human osteosarcoma tumor growth compared to vehicle-treated group (closed squares) and dissected tumors images. Scale bar represents 10 mm. All P values are two-sided. On day 19 HPMA copolymer-ALN-TNP-470 conjugate inhibited tumor growth by 96% (P = 0.001) compared with 45% (P = 0.012) of free ALN and TNP-470. Data represent mean±s.d. * P<0.05, ** P<0.03, *** P<0.05 compared with control. (E) Whole-mount confocal microscopy of mCherry-labeled MG-63-Ras human osteosarcoma tumors dissected from mice treated with FITC-labeled HPMA copolymer-ALN-TNP-470 conjugate. Scale bar represents 25 µm (n = 5 mice per group). (F) H & E and CD34 staining of control, combination- and conjugate-treated MG-63-Ras osteosarcomas inoculated s.c. in mice. (G) Dissected organs of mice treated with FITC-labeled HPMA copolymer-ALN-TNP-470 conjugate were imaged by the Maestro system showing greater intensity of FITC-fluorescence spectrum (composed images of unmixed multispectral cubes) in bone tissues then in the spleen, heart, lungs, kidneys and liver. Green represent FITC-labeled HPMA copolymer-ALN-TNP-470 conjugate spectrum.