Involvement of Tumor Lymphatic System in Translocation of Intratumorally Injected Liposomes
| Autor: | Naoto Oku, Satomi Yamaguchi Ikeuchi, Ai Okajima, Genki Nakamura, Eiichi Muraoka, Kosuke Shimizu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Vascular Endothelial Growth Factor C Melanoma Experimental Pharmaceutical Science Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine Animals Lymphangiogenesis Lymph node Lymphatic Vessels Pharmacology Tumor microenvironment General Medicine Vascular endothelial growth factor Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Lymphatic system chemistry Vascular endothelial growth factor C 030220 oncology & carcinogenesis Liposomes Cancer research Lymph Lymph Nodes Nanocarriers |
| Zdroj: | Biologicalpharmaceutical bulletin. 41(4) |
| ISSN: | 1347-5215 |
| Popis: | The tumor microenvironment is one of the key factors contributing to the efficiency of drug delivery to a tumor. It has been reported that lymphangiogenesis is induced in certain tumors. Because the lymphatic system functions as a drainage one, it is possible that tumor lymphatic vessels alter not only the tumor microenvironment, but also the distribution of drug nanocarriers accumulated in the tumor tissue. Herein, we aimed to elucidate the involvement of the tumor lymphatic system in the translocation of intratumoral liposomes to regional lymph nodes by using vascular endothelial growth factor (VEGF)-C-overexpressing B16F10 tumor-bearing mice (B16/VEGF-C). When the amount of polyethylene glycol (PEG)-modified liposomes in lymph nodes (cervical, brachial, axillary, and inguinal lymph nodes) was measured after the radiolabeled liposomes had been intratumorally injected into B16/VEGF-C-bearing mice or wild-type B16-bearing mice, the accumulation of liposomes in the axillary and inguinal lymph nodes was significantly higher on the tumor-implanted side of B16/VEGF-C-bearing mice than on that of the B16-bearing ones. On the other hand, the accumulation of liposomes in these lymph nodes on the control side (no implantation) of either type of tumor-bearing mice was very low; and no difference could be observed between the 2 sides. Furthermore, the intratumoral distribution of liposomes was observed to be located near the lymphatic vessels. These results indicate that the tumor lymphatic system contributed to the extrusion of a portion of PEG-modified liposomes from the tumor tissue, suggesting that tumor lymphangiogenesis would be one of the key factors to determine the intratumoral distribution of liposomes and their subsequent fate. |
| Databáze: | OpenAIRE |
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