Nanoparticles engineered to bind cellular motors for efficient delivery

Abstract

BackgroundDynein is a cytoskeletal molecular motor protein that transports cellular cargoes along microtubules. Biomimetic synthetic peptides designed to bind dynein have been shown to acquire dynamic properties such as cell accumulation and active intra- and inter-cellular motion through cell-to-cell contacts and projections to distant cells. On the basis of these properties dynein-binding peptides could be used to functionalize nanoparticles for drug delivery applications.ResultsHere, we show that gold nanoparticles modified with dynein-binding delivery sequences become mobile, powered by molecular motor proteins. Modified nanoparticles showed dynamic properties, such as travelling the cytosol, crossing intracellular barriers and shuttling the nuclear membrane. Furthermore, nanoparticles were transported from one cell to another through cell-to-cell contacts and quickly spread to distant cells through cell projections.ConclusionsThe capacity of these motor-bound nanoparticles to spread to many cells and increasing cellular retention, thus avoiding losses and allowing lower dosage, could make them candidate carriers for drug delivery.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0354-1) contains supplementary material, which is available to authorized users.

Effect of Clinically Used Microtubule Targeting Drugs on Viral Infection and Transport Function

“…We generated tools to monitor the movement of molecular motors kinesin and dynein along MTs in cells and analyzed the effect of compounds on this movement. We designed a dynein-binding peptide probe (DBP) based on the binding motive DynPro from the ASFV that had previously been used as an efficient dynein shuttle for gold nanoparticles [ 27 ]. For the kinesin binding peptide probe (KBP), we selected a sequence that previously showed specific binding to kinesin 1 light chain [ 28 ].…”

Biomedical nanoparticle design: What we can learn from viruses

“…Another option to achieve particle spreading was shown by Zhang et al who developed a DOX carrier system composed of dendritic peptides, which under acidic pH conditions revealed arginine rich domains that induced membrane-breaking activity [ 201 ]. The problem can be further evaded when the NPs are able to bind to the cell cytoskeleton in order to disseminate to neighboring cells, as was shown recently by Dalmau-Mena et al [ 227 ]. Their in vitro approach was based on the way viruses bind to the microtubule motor to disseminate and replicate.…”

The Peptide Functionalized Inorganic Nanoparticles for Cancer-Related Bioanalytical and Biomedical Applications

“…The peptide functionalized NPs have been extensively employed to avoid non-specific delivery-related issues in the diagnosis and therapy of cancer. Especially, the role of CPP functionalized NPs has been explored in the areas, such as molecular imaging and anticancer drug delivery, because CPPs aid in cellular internalization of various NPs without damaging the cell, and the CPP functionalized NPs can be served as cargos for intracellular transport of various species including radioactive isotopes [ 173 , 208 , 209 , 210 ], small molecules [ 208 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 ], oligonucleotides [ 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 ,…”

“…The peptide functionalized NPs have been extensively employed for targeting delivery chemodrugs from the injection site to their intracellular targets in tumorous cells [ 208 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 ]. Pan and colleagues have prepared monodispersed TAT peptide modified mesoporous silica NPs (MSNs-TAT) with high payload for nuclear-targeted drug delivery [ 211 ].…”