Using nanotechnology to deliver biomolecules from nose to brain — peptides, proteins, monoclonal antibodies and RNA

There is a growing number of biomolecules, including peptides, proteins, monoclonal antibodies and RNA, that could be potentially used for the treatment of central nervous system (CNS) diseases. However, the realization of their potential is being hampered by the extraordinary difculties these complex biomolecules have to reach the brain in therapeutically meaningful amounts. Nose-to-brain (N-to-B) delivery is now being investigated as a potential option for the direct transport of biomolecules from the nasal cavity to diferent brain areas. Here, we discuss how diferent technological approaches enhance this N-to-B transport, with emphasis on those that have shown a potential for clinical translation. We also analyse how the physicochemical properties of nanocarriers and their modifcation with cell-penetrating peptides (CPPs) and targeting ligands afect their efcacy as N-to-B carriers for biomoleculesS

Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV.This study was supported by the Spanish Secretariat of Science and Innovation and FEDER funds (grants SAF2015-67334-R and RTI2018-101082-B-I00 [MINECO/FEDER]), American National Institutes of Health (grant R21AI118411 to M.B), an unrestricted research grant from Bristol-Myers Squibb S.A.U (PfC-2015-AI424-564) to M.B, the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI17/01470) to M.G and the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI14/01058) to J.G.P, a research grant from Gilead Sciences (GLD17-00204 and GLD19-00084) to M.B, GeSIDA and the Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” (RD16/0025/0007). The Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179) to M.B and J.G.P (CPII15/00014). The “Pla estratègic de recerca i innovació en salut” (PERIS), from the Catalan Government to M.G. The Spanish Secretariat of Science and Innovation Ph.D. fellowship to A.A-G (BES-2016-076382), AGAUR-FI-B-00582 Ph.D. fellowship from the Catalan Government to O.BL, and PIF-UAB Ph.D. fellowship from Universitat Autònoma de Barcelona to R.SL.Peer reviewe