Fernández Villamarín, MarcosSousa Hervés, AnaPorto, SilviaGuldris, NoeliaMartínez Costas, José ManuelRiguera Vega, RicardoFernández Megía, Eduardo2018-07-062018-07-062017-03-28Fernandez-Villamarin, M., Sousa-Herves, A., Porto, S., Guldris, N., Martínez-Costas, J., Riguera, R., & Fernandez-Megia, E. (2017). A dendrimer–hydrophobic interaction synergy improves the stability of polyion complex micelles. Polym. Chem., 8(16), 2528-2537. doi: 10.1039/c7py00304hhttp://hdl.handle.net/10347/16976This work was financially supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) (CTQ2015‐ 69021‐R), the Consellería de Cultura, Educación e Ordenación Universitaria (GRC2014/040 and Centro Singular de Investigación de Galicia Accreditation 2016‐2019, ED431G/09), and the European Regional Development Fund (ERDF). M.F.‐V. thanks the Spanish Government for a FPU FellowshipPolyion complex (PIC) micelles incorporating PEG-dendritic copolymers display an unprecedented stability towards ionic strength that is amplified via hydrophobic interactions. The tridimensional orientation of peripheral hydrophobic linkers between charged groups and the globular/rigid dendritic scaffold maximizes this stabilization compared to PIC micelles from linear polymers. As a result, micelles stable at concentrations higher than 3 M NaCl are obtained, which represents the highest saline concentration attained with PIC micelles. Advantages of this stabilizing dendritic effect have been taken for the design of a robust, pH-sensitive micelle for the controlled intracellular release of the anticancer drug doxorubicin. This micelle displays a slightly higher toxicity, and distinctive mechanisms of cell uptake and intracellular trafficking relative to the free drug. The preparation of mixed PIC micelles by combining differently functionalized PEG-dendritic block copolymers has allowed the fine-tuning of their stability, paving the way towards the facile modulation of properties like biodegradability, drug loading, or the response to external stimulieng© The Royal Society of Chemistry 2017journal article10.1039/C7PY00304H1759-9962open access