title: Boosting the therapeutic efficiency of nanovectors: exocytosis engineering.
abstract: In this work, we developed a new general strategy, which we named "exocytosis engineering", to strongly increase the intracellular persistence of nanocarriers and thus the effective dose of transported drugs. The strategy is based on the co-loading of a drug and an exocytosis inhibitor in the nanocarrier, to hinder the high tendency of cells to remove internalized nanocarriers, limiting the pharmacological efficiency of the nanoformulation. In particular, by using a well-known chemotherapeutic drug (doxorubicin) and an efficient exocytosis inhibitor (dimethilamyloride) co-loaded in mesoporous silica nanocarriers, we demonstrated a >6-fold increase in the intracellular dose of the drug (for the same administered dose), achieving a great improvement in its therapeutic action. A strong gain in the cytotoxic effect of the drug was, in fact, observed both in several tumor cell lines and in 3D tumor spheroids. The proposed approach is versatile and broadly applicable to several classes of nanocarriers and drugs, thus opening a fascinating outlook in nanomedicine.
authors.affiliation: Nanobiointeractions&Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego, 30-16163, Genova, Italy. pierpaolo.pompa@iit.it and Center for Bio-Molecular Nanotechnologies, Istituto Italiano di Tecnologia, Via Barsanti, 73010 Arnesano, Lecce, Italy.
authors.forename: Stefania
authors.identifier: http://orcid.org/0000-0002-0967-3856
authors.initials: S
authors.lastname: Corvaglia
authors.affiliation: Nanobiointeractions&Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego, 30-16163, Genova, Italy. pierpaolo.pompa@iit.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Guarnieri
authors.affiliation: Nanobiointeractions&Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego, 30-16163, Genova, Italy. pierpaolo.pompa@iit.it and Center for Bio-Molecular Nanotechnologies, Istituto Italiano di Tecnologia, Via Barsanti, 73010 Arnesano, Lecce, Italy.
authors.forename: Pier Paolo
authors.identifier: http://orcid.org/0000-0001-7549-0612
authors.initials: PP
authors.lastname: Pompa
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D005089:Exocytosis; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D050997:Nanomedicine; D053758:Nanoparticles; D012822:Silicon Dioxide; D018874:Spheroids, Cellular / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin