TY - JOUR
T1 - Bioreducible hydrophobin-stabilized supraparticles for selective intracellular release
AU - Maiolo, Daniele
AU - Pigliacelli, Claudia
AU - Sánchez-Moreno, Paola
AU - Violatto, Martina
AU - Talamini, Laura
AU - Tirotta, Ilaria
AU - Piccirillo, Rosanna
AU - Zucchetti, Massimo
AU - Morosi, Lavinia
AU - Frapolli, Roberta
AU - Candiani, Gabriele
AU - Bigini, Paolo
AU - Metrangolo, Pierangelo
AU - Baldelli Bombelli, Francesca
N1 - Funding Information:
∇Nanobiointeractions and Nanodiagnostics, Istituto Italiano di Tecnologia, Via Morego 30, Genova, Italy. Author Contributions ∥These authors contributed equally to this work. D.M., C.P., P.M., and F.B.B. designed the study. P.M. and F.B.B. supervised the study. D.M., C.P., and P.S.M. performed the SP assembly and encapsulation studies. D.M. performed the release studies. P.S.M., D.M., L.T. and M.B.V. performed and designed cell experiments. P.B., R.P., and M.Z. designed the in vivo experiments. G.M., L.T., L.M., and R.F. performed the in vivo experiments. I.T. and C.P. performed NP synthesis. G.C. analyzed the data and supplied reagents and equipment. Funding The authors gratefully acknowledge the financial support of Regione Lombardia (Fondo per lo Sviluppo e la Coesione − FAS 2007−2013) through Fondazione Centro Europeo di Nanomedicina (CEN). P.M. gratefully acknowledges the financial support of the European Research Council (ERC) through the grant FOLDHALO (www.foldhalo.eu), no. 307108. Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2017 American Chemical Society.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017
Y1 - 2017
N2 - One of the main hurdles in nanomedicine is the low
stability of drug-nanocarrier complexes as well as the
drug delivery efficiency in the region-of-interest. Here,
we describe the use of the film-forming protein
hydrophobin HFBII to organize dodecanethiol-protected
gold nanoparticles (NPs) into well-defined supraparticles
(SPs). The obtained SPs are exceptionally stable in vivo
and efficiently encapsulate hydrophobic drug molecules.
The HFBII film prevents massive release of the
encapsulated drug, which, instead, is activated by
selective SP disassembly triggered intracellularly by
glutathione reduction of the protein film. As a
consequence, the therapeutic efficiency of an
encapsulated anticancer drug is highly enhanced (2 orders
of magnitude decrease in IC50). Biodistribution and
pharmacokinetics studies demonstrate the high stability
of the loaded SPs in the bloodstream and the selective
release of the payloads once taken up in the tissues.
Overall, our results provide a rationale for the
development of bioreducible and multifunctional
nanomedicines.
AB - One of the main hurdles in nanomedicine is the low
stability of drug-nanocarrier complexes as well as the
drug delivery efficiency in the region-of-interest. Here,
we describe the use of the film-forming protein
hydrophobin HFBII to organize dodecanethiol-protected
gold nanoparticles (NPs) into well-defined supraparticles
(SPs). The obtained SPs are exceptionally stable in vivo
and efficiently encapsulate hydrophobic drug molecules.
The HFBII film prevents massive release of the
encapsulated drug, which, instead, is activated by
selective SP disassembly triggered intracellularly by
glutathione reduction of the protein film. As a
consequence, the therapeutic efficiency of an
encapsulated anticancer drug is highly enhanced (2 orders
of magnitude decrease in IC50). Biodistribution and
pharmacokinetics studies demonstrate the high stability
of the loaded SPs in the bloodstream and the selective
release of the payloads once taken up in the tissues.
Overall, our results provide a rationale for the
development of bioreducible and multifunctional
nanomedicines.
KW - drug release
KW - gold nanoparticle
KW - hydrophobin
KW - nanobio interface
KW - self-assembly
KW - supraparticle
UR - http://www.scopus.com/inward/record.url?scp=85029915850&partnerID=8YFLogxK
U2 - 10.1021/acsnano.7b04979
DO - 10.1021/acsnano.7b04979
M3 - Article
VL - 11
SP - 9413
EP - 9423
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 9
ER -