Elongated nanoparticles
have recently been shown to have distinct
advantages over their spherical counterparts in drug delivery applications.
Cellulose nanocrystals (CNCs) have rodlike shapes in nature and have
demonstrated biocompatibility in a variety of mammalian cell lines.
In this report, CNCs are put forward as a modular platform for the
production of multifunctional rod-shaped nanoparticles for cancer
imaging and therapy. For the first time, PEGylated metal-chelating
polymers containing diethylenetriaminepentaacetic acid (DTPA) (i.e.,
mPEG-PGlu(DPTA)18-HyNic and PEG-PGlu(DPTA)25-HyNic) are conjugated to CNCs to enable the chelation of radionuclides
for diagnostic and therapeutic applications. The entire conjugation
is based on UV/vis-quantifiable bis-aryl hydrazone-bond formation,
which allows direct quantification of the polymers grafted onto the
CNCs. Moreover, it has been shown that the mean number of polymers
grafted per CNC could be controlled. The CNCs are also fluorescently
labeled with rhodamine and Alexa Fluor 488 by embedding the probes
in the polymer corona. Preliminary evaluation in a human ovarian cancer
cell line (HEYA8) demonstrated that these CNCs are nontoxic and their
penetration properties can be readily assessed in multicellular tumor
spheroids (MCTSs) by optical imaging. These findings provide support
for biomedical applications of CNCs, and further in vitro and in vivo
studies are warranted to evaluate their potential as imaging and therapeutic
agents for cancer treatment.
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