Mesoporous silica templated-albumin nanoparticles with high doxorubicin payload for drug delivery assessed with a 3-D tumor cell model

• Published in: Biochimica et biophysica acta. General subjects Vol. 1863; no. 2; pp. 332 - 341
• Main Authors: Ménard, Mathilde, Meyer, Florent, Parkhomenko, Ksenia, Leuvrey, Cédric, Francius, Grégory, Bégin-Colin, Sylvie, Mertz, Damien
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2019; Elsevier
• Subjects: adsorption; Chemical Sciences; crosslinking; doxorubicin; hepatoma; human serum albumin; humans; nanocapsules; nanocarriers; nanoparticles; neoplasm cells; porous media; silica
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2018.10.020

Human serum albumin (HSA) nanoparticles emerge as promising carriers for drug delivery. Among challenges, one important issue is the design of HSA nanoparticles with a low mean size of ca. 50 nm and having a high drug payload. The original strategy developed here is to use sacrificial mesoporous nanosilica templates having a diameter close to 30 nm to drive the protein nanocapsule formation. This new approach ensures first an efficient high drug loading (ca. 30%) of Doxorubicin (DOX) in the porous silica by functionalizing silica with an aminosiloxane layer and then allows the one-step adsorption and the physical cross-linking of HSA by modifying the silica surface with isobutyramide (IBAM) groups. After silica template removal, homogenous DOX-loaded HSA nanocapsules (30–60 nm size) with high drug loading capacity (ca. 88%) are thus formed. Such nanocapsules are shown efficient in multicellular tumor spheroid models (MCTS) of human hepatocarcinoma cells by their significant growth inhibition with respect to controls. Such a new synthesis approach paves the way toward new protein based nanocarriers for drug delivery. [Display omitted]