Bioreducible Hydrophobin-Stabilized Supraparticles for Selective Intracellular Release
Maiolo, D.a, Pigliacelli, C.a,d, Sánchez Moreno, P.a,e, Violatto, M.B.b, Talamini, L.b, Tirotta, I.a, Piccirillo, R.b, Zucchetti, M.b, Morosi, L.b, Frapolli, R.b, Candiani, G.a, Bigini, P.b, Metrangolo, P.a,c, Baldelli Bombelli, F.a
a Interdepartmental Laboratory of Nanomedicine (NanoMedLab), Laboratory of Supramolecular and BioNano Materials (SupraBioNanoLab), Fondazione Centro Europeo Nanomedicina (CEN), Department of Chemistry, Materials, and Chemical Engineering Giulio Natta, Politecnico di Milano, via L. Mancinelli 7, Milan, 20131, Italy
b IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, I-Milano, 20156, Italy
c VTT-Technical Research Centre of Finland Ltd, Biologinkuja 7, Espoo, FI-02044, Finland
d Hyber Center of Excellence, Department of Applied Physics, Aalto University, Puumiehenkuja 2, Espoo, FI-00076, Finland
e Nanobiointeractions and Nanodiagnostics, Istituto Italiano di Tecnologia, Via Morego 30, Genova, Italy
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.
