The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth and metastatic potential within the intact organism. Magnetic Resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. Accordingly, we have developed carbon- and gold-nanoparticles coupled to gadolinium(III) [Gd(III)] chelates for T1-weighted MR imaging that demonstrated remarkable properties for cell tracking in vitro and in vivo. We created nanodiamond-Gd(III) aggregates (NDG) by peptide coupling Gd(III) chelates to aminated nanodiamonds. NDG had high relaxivity independent of field strength (unprecedented for Gd(III)-nanoparticle conjugates), and demonstrated a 300-fold increase in cellular delivery of Gd(III) compared to clinical Gd(III) chelates. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1-weighted MRI for 26 days in vivo, longer than reported for other MR CAs or nuclear agents. Further, theranostic nanodiamond-gadolinium(III)-doxorubicin (ND-Gd-Dox) aggregates were generated by conjugating doxorubicin (ND-Gd-Dox), which enabled efficient cancer chemotherapy in breast cancer cells. Further, we synthesized Gd(III)-gold nanoconjugates (Gd@AuNPs) with varied chelate structure and nanoparticle-chelate linker length. Significantly enhanced cell labeling was demonstrated compared to previous gadolinium-gold-DNA nanoconstructs. Differences in Gd(III) loading, surface packing and cell uptake were observed between four different Gd@AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd@AuNPs afforded 23.6 ± 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 µM. This efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previously Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Finally, Gd@AuNPs were the first MR CAs of any type to effectively image the pancreas in vivo. In summary, both Gd@AuNPs and NDG support future MR-mediated cell tracking and theranostic applications in whole-animal models.

Last modified

• 02/20/2018

Creator

• Nikhil Ram Mohan

DOI

• https://doi.org/10.21985/N2038K

Subject

• Interdepartmental Biological Sciences (IBiS) Graduate Program

Keyword

• Nanotechnology
• Chemistry

Date created

• 2016-01-01

Resource type

• Dissertation

Rights statement

• In Copyright