Lanthanide-based upconverting nanoparticles (UCNP's) are able to efficiently convert near infrared excitation energy into visible or higher energy near infrared light, thereby presenting an attractive platform for construction of biological imaging agents. However, lack of solubility and difficulty in their surface modifications hampered development of UCNP's as general imaging agents. Previously, we have demonstrated that shape-persistent polyglutamic dendrimers, exhibiting multiple carboxylate groups as their termini, are of tight bind to UCNP surfaces, thus stabilizing them in aqueous solutions and converting them into bio-compatible imaging probes.1 However, solubility imparted by polycarboxylates was found to be negatively impacted by the presence of divalent metal cations and various macromolecules (proteins, lipids etc), which are abundant in biological systems. In this work, we report extension of our approach using Janus-type dendrimers, in which one half of the dendrimer surface features carboxylates for binding to UCNP surfaces and another is highly hydrophilic, but neutral as a result of extensive PEG-ylation. The new dendritic UCNP's proved to have superior stability and biocompatibility and allowed high-resolution imaging of brain vasculature in mice up to 1 mm deep into the cortex by means of multiphoton microscopy with continuous-wave infrared excitation sources. The synthesis of PEGylated Janus-dendrimers as well as the method of dendrimerization of UCNP's has been optimized and scaled up, thus presenting a new generally applicable methodology.
1 Esipova, T. V.; Ye, X.; Collins, J. E.; Sakadžić, S.; Mandeville, E. T.; Murray, C. B.; Vinogradov, S. A. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 20826.
Support of the NIH grant EB018464 is gratefully acknowledged.
Mirna El Khatib, Shane Plunkett, Ikbal Sencan, Joshua E. Collins, Sava Sakadžić, and Sergei Vinogradov, "Imaging deep in the brain using dendritic upconverting nanoparticles (Conference Presentation)," Proc. SPIE 10497, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVI, 1049712 (Presented at SPIE BiOS: January 31, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2290952.5751463354001.
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