TY - JOUR
T1 - Smart design of universally decorated nanoparticles for drug delivery applications driven by active transport
AU - Halbi, Gal
AU - Fayer, Itay
AU - Aranovich, Dina
AU - Gat, Shachar
AU - Pavan, Mariela J.
AU - Nachmias, Dikla
AU - Sanchez, Daniel Sevilla
AU - Brik, Ashraf
AU - Granek, Rony
AU - Bernheim-Groswasser, Anne
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to EDP Sciences, SIF and Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - Abstract: Targeting the cell nucleus remains a challenge for drug delivery. Here, we present a universal platform for the smart design of nanoparticle (NP) decoration that is based on: (i) a spacer polymer, commonly biotin-polyethylene-glycol-thiol, whose grafting density and molecular weight can be tuned for optimized performance, and (ii) protein binding peptides, such as cell penetrating peptides (CPPs), cancer-targeting peptides, or nuclear localization signal (NLS) peptides, that are linked to the PEG free-end by universal chemistry. We manifested our platform with two different bromo-acetamide (Br-Ac) modified NLSs. We used cell extract-based and live cell assays to demonstrate the recruitment of dynein motor proteins, which drive the NP active transport toward the nucleus, and the enhancement of cellular and nuclear entry, manifesting the properties of NLS as a CPP. Our control of the NP decoration scheme, and the modularity of our platform, carry great advantages for nano-carrier design for drug delivery applications. Graphical abstract: [Figure not available: see fulltext.]
AB - Abstract: Targeting the cell nucleus remains a challenge for drug delivery. Here, we present a universal platform for the smart design of nanoparticle (NP) decoration that is based on: (i) a spacer polymer, commonly biotin-polyethylene-glycol-thiol, whose grafting density and molecular weight can be tuned for optimized performance, and (ii) protein binding peptides, such as cell penetrating peptides (CPPs), cancer-targeting peptides, or nuclear localization signal (NLS) peptides, that are linked to the PEG free-end by universal chemistry. We manifested our platform with two different bromo-acetamide (Br-Ac) modified NLSs. We used cell extract-based and live cell assays to demonstrate the recruitment of dynein motor proteins, which drive the NP active transport toward the nucleus, and the enhancement of cellular and nuclear entry, manifesting the properties of NLS as a CPP. Our control of the NP decoration scheme, and the modularity of our platform, carry great advantages for nano-carrier design for drug delivery applications. Graphical abstract: [Figure not available: see fulltext.]
UR - http://www.scopus.com/inward/record.url?scp=85169396675&partnerID=8YFLogxK
U2 - 10.1140/epje/s10189-023-00331-5
DO - 10.1140/epje/s10189-023-00331-5
M3 - Article
C2 - 37653248
AN - SCOPUS:85169396675
SN - 1292-8941
VL - 46
JO - European Physical Journal E
JF - European Physical Journal E
IS - 9
M1 - 74
ER -
