Bioreducible hydrophobin-stabilized supraparticles for selective intracellular release

Daniele Maiolo; Claudia Pigliacelli; Paola Sánchez-Moreno; Martina Violatto; Laura Talamini; Ilaria Tirotta; Rosanna Piccirillo; Massimo Zucchetti; Lavinia Morosi; Roberta Frapolli; Gabriele Candiani; Paolo Bigini; Pierangelo Metrangolo; Francesca Baldelli Bombelli

doi:10.1021/acsnano.7b04979

Bioreducible hydrophobin-stabilized supraparticles for selective intracellular release

Daniele Maiolo
, Claudia Pigliacelli
, Paola Sánchez-Moreno
, Martina Violatto
, Laura Talamini
, Ilaria Tirotta
, Rosanna Piccirillo
, Massimo Zucchetti
, Lavinia Morosi
, Roberta Frapolli
, Gabriele Candiani
, Paolo Bigini
, Pierangelo Metrangolo
, Francesca Baldelli Bombelli

Istituto di Ricerche Farmacologiche Mario Negri
Polytechnic University of Milan

Research output: Contribution to journal › Article › Scientific › peer-review

53 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	9413-9423
Number of pages	11
Journal	ACS Nano
Volume	11
Issue number	9
DOIs	https://doi.org/10.1021/acsnano.7b04979
Publication status	Published - 26 Sept 2017
MoE publication type	A1 Journal article-refereed

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

drug release
gold nanoparticle
hydrophobin
nanobio interface
self-assembly
supraparticle

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10.1021/acsnano.7b04979Licence: CC BY-NC-ND

Cite this

Maiolo, D., Pigliacelli, C., Sánchez-Moreno, P., Violatto, M., Talamini, L., Tirotta, I., Piccirillo, R., Zucchetti, M., Morosi, L., Frapolli, R., Candiani, G., Bigini, P., Metrangolo, P., & Baldelli Bombelli, F. (2017). Bioreducible hydrophobin-stabilized supraparticles for selective intracellular release. ACS Nano, 11(9), 9413-9423. https://doi.org/10.1021/acsnano.7b04979

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abstract = "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.",

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Maiolo, D, Pigliacelli, C, Sánchez-Moreno, P, Violatto, M, Talamini, L, Tirotta, I, Piccirillo, R, Zucchetti, M, Morosi, L, Frapolli, R, Candiani, G, Bigini, P, Metrangolo, P & Baldelli Bombelli, F 2017, 'Bioreducible hydrophobin-stabilized supraparticles for selective intracellular release', ACS Nano, vol. 11, no. 9, pp. 9413-9423. https://doi.org/10.1021/acsnano.7b04979

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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

PY - 2017/9/26

Y1 - 2017/9/26

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.

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KW - hydrophobin

KW - nanobio interface

KW - self-assembly

KW - supraparticle

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ER -

Bioreducible hydrophobin-stabilized supraparticles for selective intracellular release

Abstract

Funding

UN SDGs

Keywords

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