Preferential Tumor Accumulation of Polyglycerol Functionalized Nanodiamond Conjugated with Cyanine Dye Leading to Near‐Infrared Fluorescence In Vivo Tumor Imaging

Abstract

Preferential accumulation of nanoparticles in a tumor is realized commonly by combined effects of active and passive targeting. However, passive targeting based on an enhanced permeation and retention (EPR) effect is not sufficient to observe clear tumor fluorescence images in most of the in vivo experiments using tumor‐bearing mice. Herein, polyglycerol‐functionalized nanodiamonds (ND‐PG) conjugated with cyanine dye (Cy7) are synthesized and it is found that the resulting ND‐PG‐Cy7 is preferentially accumulated in the tumor, giving clear fluorescence in in vivo and ex vivo fluorescence images. One of the plausible reasons is the longer in vivo blood circulation time of ND‐PG‐Cy7 (half‐life: 58 h determined by the pharmacokinetic analysis) than that of other nanoparticles (half‐life: <20 h in most of the previous reports). In a typical example, the fluorescence intensity of tumors increases due to continuous tumor accumulation of ND‐PG‐Cy7, even more than one week postinjection. This may be owing to the stealth effect of PG that was reported previously, avoiding recognition and excretion by reticuloendothelial cells, which are abundant in liver and spleen. In fact, the fluorescence intensities from the liver and spleen is similar to those from other organs, while the tumor exhibits much stronger fluorescence in the ex vivo image.

Influencing factors and strategies of enhancing nanoparticles into tumors in vivo

“…Although surface modification can reduce the binding of additional biomolecules, the binding of some biomolecules may still occur 138 . From the thermodynamic point of view, non-ionic and hydrophilic polymers are considered to have higher potential to prevent protein adsorption 139 , 140 . Recently, Zou et al.…”

Surface Modification of Fluorescent Nanodiamonds for Biological Applications

“…PG has been shown to overcome many of the drawbacks of PEG. PG can be polymerized on the surface of hydroxylated and/or carboxylated NDs through ring-opening multi-branching polymerization of glycidol [ 25 , 26 , 116 , 117 ]. This type of reaction is termed “grafted from”.…”

“…PG-modified NDs exhibit good solubility in a variety of buffers and methanol. Owing to decreased nonspecific adsorption, PG-functionalized NDs showed much higher tumor accumulation [ 117 ]. In addition to PG, poly(oligo(ethylene glycol) methyl ether methacrylate), poly( N -isopropylacrylamide), and poly(2-methacryloyloxyethyl phosphorylcholine) have been employed to functionalize NDs via reversible addition−fragmentation chain transfer, free radical, and metal-free atom transfer radical polymerization in the “grafted from” approach, respectively [ 118 , 119 , 120 ].…”

Graphene Oxide‐Cyclic R10 Peptide Nuclear Translocation Nanoplatforms for the Surmounting of Multiple‐Drug Resistance

“…[ 35,36 ] The obtained nanographene oxide (nGO) contains a large number of epoxy and hydroxyl functional groups on the basal plane and carboxyl on its edges. [ 36 ] Moreover, hyperbranched polyglycerol (hPG) with great potential in a wide range of biomedical applications, including drug delivery, tissue engineering, and pathogen interactions, [ 37,38 ] has been used to improve the biological safety and performances of nanomaterials, such as graphene. [ 39–41 ]…”