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Anticancer and antiangiogenic activity of surfactant-free nanoparticles based on self-assembled polymeric derivatives of vitamin E: Structure-activity relationship
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2015
- Publisher :
- American Chemical Society, 2015.
-
Abstract
- ¿-Tocopheryl succinate (¿-TOS) is a well-known mitochondrially targeted anticancer compound, however, it is highly hydrophobic and toxic. In order to improve its activity and reduce its toxicity, new surfactant-free biologically active nanoparticles (NP) were synthesized. A methacrylic derivative of ¿-TOS (MTOS) was prepared and incorporated in amphiphilic pseudoblock copolymers when copolymerized with N-vinylpyrrolidone (VP) by free radical polymerization (poly(VP-co-MTOS)). The selected poly(VP-co-MTOS) copolymers formed surfactant-free NP by nanoprecipitation with sizes between 96 and 220 nm and narrow size distribution, and the in vitro biological activity was tested. In order to understand the structure-activity relationship three other methacrylic monomers were synthesized and characterized: MVE did not have the succinate group, SPHY did not have the chromanol ring, and MPHY did not have both the succinate group and the chromanol ring. The corresponding families of copolymers (poly(VP-co-MVE), poly(VP-co-SPHY), and poly(VP-co-MPHY)) were synthesized and characterized, and their biological activity was compared to poly(VP-co-MTOS). Both poly(VP-co-MTOS) and poly(VP-co-MVE) presented triple action: reduced cell viability of cancer cells with little or no harm to normal cells (anticancer), reduced viability of proliferating endothelial cells with little or no harm to quiescent endothelial cells (antiangiogenic), and efficiently encapsulated hydrophobic molecules (nanocarrier). The anticancer and antiangiogenic activity of the synthesized copolymers is demonstrated as the active compound (vitamin E or ¿-tocopheryl succinate) do not need to be cleaved to trigger the biological action targeting ubiquinone binding sites of complex II. Poly(VP-co-SPHY) and poly(VP-co-MPHY) also formed surfactant-free NP that were also endocyted by the assayed cells; however, these NP did not selectively reduce cell viability of cancer cells. Therefore, the chromanol ring of the vitamin E analogues has an important role in the biological activity of the copolymers. Moreover, when succinate moiety is substituted and vitamin E is directly linked to the macromolecular chain through an ester bond, the biological activity is maintained.<br />Authors acknowledge Dr. Gema Rodriǵ uez, Lautaro Biancotto, David Goḿ ez, and Rosa Ana Ramiŕ ez for their help in AFM, SEM/TEM, and cell culture experiments. Authors also thank Dr. M.P. Murphy for providing MitoQ for the experiments. This work was funded by the Spanish Ministry of Economy and Competitiveness (MAT2010−18155), Eugenio Rodriǵ uez Pascual Foundation, CIBER BBN-ECO Foundation project, and the European University of Madrid.
- Subjects :
- Polymers and Plastics
Polymers
Radical polymerization
alpha-Tocopherol
Nanoparticle
Bioengineering
Salud
Angiogenesis Inhibitors
Antineoplastic Agents
Ring (chemistry)
Vitaminas
Biomaterials
Structure-Activity Relationship
Surface-Active Agents
Neoplasms
Amphiphile
Materials Chemistry
Copolymer
Structure–activity relationship
Organic chemistry
Vitamina
Humans
Vitamin E
Ciencias médicas
Cell Proliferation
Neovascularization, Pathologic
Chemistry
Biological activity
Cáncer
Combinatorial chemistry
In vitro
MCF-7 Cells
Methacrylates
Nanoparticles
Hydrophobic and Hydrophilic Interactions
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....43cedb9d57458927427333c195efc332