ARTICLE pubs.acs.org/Biomac
pH-Responsive Polysaccharide-Based Polyelectrolyte Complexes As Nanocarriers for Lysosomal Delivery of Therapeutic Proteins Marina I. Giannotti,*,†,‡,§ Olga Esteban,†,|| Mireia Oliva,†,^ María F. García-Parajo,†,||,# and Fausto Sanz*,†,‡,§ †
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, 50018, Spain Physical Chemistry Department, University of Barcelona (UB), Martí i Franques 1-3, Barcelona,08028, Spain § Nanoprobes & Nanoswitches Group and BioNanoPhotonics Group, Institute for Bioengineering of Catalonia (IBEC), Baldiri i Reixac 15-21, Barcelona, 08028, Spain ^ Pharmaceutical Technology Unit, School of Pharmacy, University of Barcelona (UB), Av. Joan XXIII s/n, Barcelona, 08028, Spain # ICREA-Institucio Catalana de Recerca i Estudis Avanc-ats, Barcelona, 08010, Spain )
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bS Supporting Information ABSTRACT: Nanopharmaceutics composed of a carrier and a protein have the potential to improve the activity of therapeutical proteins. Therapy for lysosomal diseases is limited by the lack of effective protein delivery systems that allow the controlled release of specific proteins to the lysosomes. Here we address this problem by developing functional polyelectrolytebased nanoparticles able to promote acidic pH-triggered release of the loaded protein. Trimethyl chitosan (TMC) was synthesized and allowed to form polyelectrolyte complexes (PECs) with the lysosomal enzyme R-GAL through self-assembly and ionotropic gelation, with average particle size
