Florentina Pascale1, Laurent Bédouet2, Afchine Fazel3, Julien Namur4, Saida Homayra Ghegediban4, Isabelle Schwartz Cornil5, Michel Wassef3, Laurence Moine6, Alexandre Laurent3,7,8. 1. ArchimMed SARL, 12, rue Charles de Gaulle, 78350, Jouy en Josas, France. florentina.pascale@archimmed.com. 2. Occlugel, 12, rue Charles de Gaulle, 78350, Jouy en Josas, France. 3. Hôpital Lariboisière, 2, Rue Ambroise Paré, 75010, Paris, France. 4. ArchimMed SARL, 12, rue Charles de Gaulle, 78350, Jouy en Josas, France. 5. Laboratoire de Virologie et Immunologie Moleculaires, Institut National de la Recherche Agronomique, Domaine de Vilvert, Jouy en Josas, France. 6. Institut Galien Paris Sud, CNRS, Université Paris-Saclay, 5, rue Jean-Baptiste Clément, 92296, Châtenay-Malabry Cedex, France. 7. Université Paris Diderot-Paris 7, 75205, Paris Cedex 13, France. 8. Cr2i, INRA, Domaine de Vilvert, 78352, Jouy en Josas, France.
Abstract
PURPOSE: To assess the lymphatic transport of microparticles of 100 nm, 1 μm and 10 μm subcutaneously injected into the breast area of healthy and tumor-bearing rabbits, and to analyze their location in lymph node (LN) in relation to malignant cells. METHODS: Female rabbits (n = 9) bearing a VX2 tumor in one thoracic mammary gland were subcutaneously injected at D15 with polystyrene fluorescent particles around the nipple, on the tumor and on the healthy sides. The tumor and the LN measured by ultrasound at D9, D15 and D20 were explanted at D20. The LN metastases were evaluated by cytokeratin staining. LN uptake of the particles was measured by quantifying the green fluorescence surface in hot spot regions of healthy and pathologic LN. RESULTS: All animals developed mammary tumors. Metastases were found in 39% of LN from the tumor side. LN invasion was significantly lower for the 10 μm group versus the 100 nm group (p < 0.0348). The fully invaded area of metastatic LN contained significantly less 100 nm and 1 μm particles compared to the low and non-invaded regions and to the healthy LN. In the invaded LN, the 1 μm MS occupied more surface than the 100 nm particles. CONCLUSIONS: 1 μm MS arrived numerously into the areas low-invaded and non-invaded by the tumoral cells of the pathologic LN, but they were very rare in the fully invaded regions. Compared to the 100 nm nanospheres, the 1 μm were better retained (20 times) into the sentinel LN, showing the advantage of micrometric particles for lymph-targeted chemotherapy when injected before complete invasion by metastases.
PURPOSE: To assess the lymphatic transport of microparticles of 100 nm, 1 μm and 10 μm subcutaneously injected into the breast area of healthy and tumor-bearing rabbits, and to analyze their location in lymph node (LN) in relation to malignant cells. METHODS: Female rabbits (n = 9) bearing a VX2 tumor in one thoracic mammary gland were subcutaneously injected at D15 with polystyrene fluorescent particles around the nipple, on the tumor and on the healthy sides. The tumor and the LN measured by ultrasound at D9, D15 and D20 were explanted at D20. The LN metastases were evaluated by cytokeratin staining. LN uptake of the particles was measured by quantifying the green fluorescence surface in hot spot regions of healthy and pathologic LN. RESULTS: All animals developed mammary tumors. Metastases were found in 39% of LN from the tumor side. LN invasion was significantly lower for the 10 μm group versus the 100 nm group (p < 0.0348). The fully invaded area of metastatic LN contained significantly less 100 nm and 1 μm particles compared to the low and non-invaded regions and to the healthy LN. In the invaded LN, the 1 μm MS occupied more surface than the 100 nm particles. CONCLUSIONS: 1 μm MS arrived numerously into the areas low-invaded and non-invaded by the tumoral cells of the pathologic LN, but they were very rare in the fully invaded regions. Compared to the 100 nm nanospheres, the 1 μm were better retained (20 times) into the sentinel LN, showing the advantage of micrometric particles for lymph-targeted chemotherapy when injected before complete invasion by metastases.
Authors: Rong Liu; Denis M Gilmore; Kimberly Ann V Zubris; Xiaoyin Xu; Paul J Catalano; Robert F Padera; Mark W Grinstaff; Yolonda L Colson Journal: Biomaterials Date: 2012-12-08 Impact factor: 12.479