Influence of side chain length on fluorescence intensity of ROMP-based polymeric nanoparticles and their tumor specificity in in-vivo tumor imaging.
In this study, amphiphilic brush-like copolymers conjugated with short alkyl or long polymeric chains of various lengths are synthesized using ring-opening metathesis polymerization (ROMP) of substituted norbornadiene monomers followed by chemical transformations. These amphiphilic copolymers form spherical self-assemblies in aqueous media with diameters of 132-244 nm. The low critical aggregation concentration of these assemblies (2.5 × 10(-3) -1.4 × 10(-5)  g/L) indicates that they are quite stable in dilute conditions. An appropriate length of polymer side chain that conjugates the polymer backbone with a hydrophobic ICG (indocyanine green) moiety enhanced the fluorescence intensities of these self-assemblies in aqueous solution as well as in tumor-bearing mice. A longer side chain conjugated with tumor targeting agents could significantly affect the tumor specificity of self-assemblies to a greater extent. The self-assemblies bearing hydrophilic tumor targeting agents, such as a glucosamine molecule and a cyclic RGD (arginine-glycine-asparatic acid) peptide, accumulated in tumor tissues with high selectivity, while those having a hydrophobic targeting agent, such as folate moieties, accumulated in tumor sites with low selectivity. The results demonstrated here unambiguously indicate that the fluorescence intensity and tumor specificity of self-assemblies are strongly affected by the length of side chains that conjugate with dyes and targeting agents.
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
Koji
K
Miki
Kazuaki
K
Oride
Akinori
A
Kimura
Yoshiaki
Y
Kuramochi
Hideki
H
Matsuoka
Hiroshi
H
Harada
Masahiro
M
Hiraoka
Kouichi
K
Ohe
D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D005492:Folic Acid / Q000494:pharmacology; D005944:Glucosamine / Q000494:pharmacology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D011108:Polymers / Q000737:chemistry*
D005456:Fluorescent Dyes; D009842:Oligopeptides; D011108:Polymers; C047981:arginyl-glycyl-aspartic acid; D005492:Folic Acid; D005944:Glucosamine