10.6084/m9.figshare.5314564.v1 Simone Villani Simone Villani Renata Adami Renata Adami Ernesto Reverchon Ernesto Reverchon Anna Maria Ferretti Anna Maria Ferretti Alessandro Ponti Alessandro Ponti Marilena Lepretti Marilena Lepretti Ivana Caputo Ivana Caputo Lorella Izzo Lorella Izzo pH-sensitive polymersomes: controlling swelling via copolymer structure and chemical composition Taylor & Francis Group 2017 pH-sensitive polymersomes ATRP vesicles controlled drug-release 2017-08-16 09:56:40 Journal contribution https://tandf.figshare.com/articles/journal_contribution/pH-sensitive_polymersomes_controlling_swelling_via_copolymer_structure_and_chemical_composition/5314564 <p>pH-sensitive vesicles used as drug delivery systems (DDSs) are generally composed of protonable copolymers. The disaggregation of these nanoparticles (NPs) during drug release implies the dispersion of positively charged cytotoxic polyelectrolytes in the human body. To alleviate such issue, we synthesised A(BC)<i><sub>n</sub></i> amphiphilic block copolymers with linear (<i>n</i> = 1) and branched (<i>n</i> = 2) architectures to obtain pH-sensitive vesicles capable of releasing drugs in acidic conditions via controlled swelling instead of disaggregation. We obtained this feature by fine-tuning the relative amount of pH-sensitive and hydrophobic monomers. We studied pH-driven swelling by measuring NPs size in neutral and acidic conditions, the latter typical of tumours or inflamed tissues (pH∼6) and lysosomes (pH∼4.5). Dynamic light scattering (DLS) and zeta potential data provided useful indications about the influence of architecture and chemical composition on NPs swelling, stability and polycation release. Results demonstrated that vesicles made of linear copolymers with ∼22–28% in mol of protonable monomers in the ‘BC’ block swelled more than other species following a pH change from pH 7.4 to pH 4.5. We finally evaluated the cytotoxicity of vesicles composed of linear species, and paclitaxel (PTX) release from the latter in both cancer and normal cells.</p>