1. Effective treatment of the primary tumor and lymph node metastasis by polymeric micelles with variable particle sizes.
- Author
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Mei L, Rao J, Liu Y, Li M, Zhang Z, and He Q
- Subjects
- Animals, Cell Line, Tumor, Mice, Inbred BALB C, Micelles, Particle Size, Antineoplastic Agents administration & dosage, Drug Delivery Systems, Lymphatic Metastasis prevention & control, Neoplasms drug therapy, Paclitaxel administration & dosage, Phosphatidylethanolamines administration & dosage, Polyethylene Glycols administration & dosage
- Abstract
Nanoparticles (NPs) offer new solutions for the diagnosis and treatment of tumors. However, the anti-tumor effect has not been greatly improved. Tumors are easily spread through the lymphatic system while the traditional NPs (~100 nm) can hardly reach lymph nodes for the treatment of metastasis. In addition, the NPs with fixed particle size cannot achieve efficient "penetration" and long-term "retention" simultaneously. Herein, we established "transformable" micelles modified with azide/alkyne groups for click chemical reaction. Not surprisingly, the small micelles (~25 nm) could effectively target lymph nodes, limiting the growth of the metastases associated with their size-regulated abilities to extravasate from the vasculature. Tumor lymph node metastasis dropped by 66.7%. After reaching primary tumors, cycloaddition reaction occurred between groups on micelles, resulting in the formation of aggregates. The strategy resulted in improved retention of the micelles in 4 T1 cells both in vitro and in vivo owing to the decreasing of nanoparticle exocytosis and minimizing the backflow to the bloodstream. Enhanced cytotoxicity on 4 T1 cells and improved antitumor efficacy were also observed. S-PTX (+) exhibited 76.23% tumor suppression, and tumor mass at the end of the treatment also showed the best tumor inhibitory effect. In conclusion, this drug delivery system provides a strategy for effective treatment of the primary tumor and lymphatic metastasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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