Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity
MetadataShow full item record
Dual-functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to sequentially react with different amino compounds is exploited; doxorubicin (DOX) and 1-(5-amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO3A-tBu-NH2)—a chelating agent effective for the complexation of Gadolinium ions (Gd). The activated ester group is employed to attach the DO3A chelating agent, while the aldehyde groups are exploited for DOX conjugation, providing a controlled release mechanism for DOX in acidic environments. DOX/Gd-loaded nanoparticles are rapidly taken up by MCF-7 breast cancer cells, subsequently releasing DOX as demonstrated using in vitro fluorescence lifetime imaging microscopy (FLIM). Endosomal, DOX release is observed, using a phasor plot representation of the fluorescence lifetime data, showing an increase of native DOX with time. The MRI properties of the stars are assessed and the relaxivity of Gd loaded in stars is three times higher than conventional organic Gd/DO3A complexes. The DOX/Gd-conjugated nanoparticles yield a similar IC50 to native DOX for breast cancer cell lines, confirming that DOX integrity is conserved during nanoparticle attachment and release.
Showing items related by title, author, creator and subject.
Vellore Janarthanan, Mohanraj (2003)Delivery of complex molecules such as peptides, proteins, oligonucleotides and plasmids is an intensively studied subject, which has attracted considerable medical and pharmaceutical interest. Encapsulation of these ...
The Precise Molecular Location of Gadolinium Atoms has a Significant Influence on the Efficacy of Nanoparticulate MRI Positive Contrast AgentsLi, Y.; Laurent, S.; Esser, L.; Vander Elst, L.; Muller, R.; Lowe, Andrew; Boyer, C.; Davis, T. (2014)In this work, we studied the influence of the structure of macromolecular ligands on the relaxivity of gadolinium contrast agents constructed as nanoparticle systems. Macromolecular ligands were assembled as single-molecule ...
Smith, B.; Soria, Roberto; Struck, C.; Giroux, M.; Swartz, D.; Yukita, M. (2014)Hinge clumps are luminous knots of star formation near the base of tidal features in some interacting galaxies. We use archival Hubble Space Telescope (HST) UV/optical/IR images and Chandra X-ray maps along with Galaxy ...