The need to maximize tumor uptake, and minimize uptake by other organs, is a common and formidable hurdle for many drug delivery and imaging applications. To attain this goal, new chemistries are required that attach multiple functional groups to substrates (substrates = nanoparticles, proteins, peptides), so a single probe's fate in biological systems can be easily detected by the different modalities needed to ascertain probe disposition at the cellular, tissue and whole animal levels. In addition, these chemistries need to simultaneously alter the physical properties of the probe (e.g., hydrophilicity, charge), to maximize tumor targeting. Finally, it is essential that these new chemistries provide probes with the rigorously defined chemical properties needed for the clinical translation. A solution to these three problems in multifunctional materials design lies in a new class of reagents termed Multifunctional Single Attachment Point or MSAP's. MSAP's consist of a short peptide scaffolds to which multiple functional groups and a single reactive group, such an NHS ester or maleimide, are attached. The RG of the MSAP then attaches the MSAP (and its multiple functional groups) to a substrate in a single reaction, to yield a multifunctional probe. (Note: MSAP reagent + substrate = multifunctional probe). The functional groups employed in an MSAP reagent (i) permit the disposition of the resulting probe to be determined in biological systems (functional groups can be chromophores, fluorochromes, chelating groups or immunoreactive haptens) and, (ii) permit the physical properties of the resulting probe to be controlled and optimized (functional groups = hydrophilic polymers or a small charged structures). Multifiunctional MSAP based probes achieve a stoichiometry between multiple functional groups based on the MSAP reagent, a feature essential for the eventual clinical use of multifunctional materials. We shall expand MSAP chemistry by synthesizing MSAP reagent panels and demonstrate their broad applicability with three different types of substrates: (i) a NP substrate, obtaining enhanced glioma targeting), (ii) an anti-CEA scFv antibody substrate (enhanced tumor CEA targeting) and, (iii) a bombesin (BN) peptide substrate (enhanced tumor GRP receptor targeting).
Our goal is the development of a new type of reagent for designing multifunctional nanomaterials that will enable materials to be detected by different imaging modalities and which will enable them to target tumors more effectively.
|Chen, Howard H; Yuan, Hushan; Cho, Hoonsung et al. (2015) Cytoprotective nanoparticles by conjugation of a polyhis tagged annexin V to a nanoparticle drug. Nanoscale 7:2255-9|
|Wilks, Moses Q; Normandin, Marc D; Yuan, Hushan et al. (2015) Imaging PEG-like nanoprobes in tumor, transient ischemia, and inflammatory disease models. Bioconjug Chem 26:1061-9|
|Normandin, Marc D; Yuan, Hushan; Wilks, Moses Q et al. (2015) Heat-Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. Angew Chem Int Ed Engl 54:13002-6|
|Guo, Yanyan; Yuan, Hushan; Claudio, Natalie M et al. (2014) PEG-like nanoprobes: multimodal, pharmacokinetically and optically tunable nanomaterials. PLoS One 9:e95406|
|Guo, Yanyan; Yuan, Hushan; Cho, Hoonsung et al. (2013) High efficiency diffusion molecular retention tumor targeting. PLoS One 8:e58290|
|Cho, Hoonsung; Alcantara, David; Yuan, Hushan et al. (2013) Fluorochrome-functionalized nanoparticles for imaging DNA in biological systems. ACS Nano 7:2032-41|
|Buckle, Tessa; Kuil, Joeri; van den Berg, Nynke S et al. (2013) Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS. PLoS One 8:e48324|
|Guo, Yanyan; Yuan, Hushan; Rice, William L et al. (2012) The PEG-fluorochrome shielding approach for targeted probe design. J Am Chem Soc 134:19338-41|
|Bunschoten, Anton; Buckle, Tessa; Visser, Nils L et al. (2012) Multimodal interventional molecular imaging of tumor margins and distant metastases by targeting Ã½Ã½vÃ½Ã½3 integrin. Chembiochem 13:1039-45|
|Alcantara, David; Guo, Yanyan; Yuan, Hushan et al. (2012) Fluorochrome-functionalized magnetic nanoparticles for high-sensitivity monitoring of the polymerase chain reaction by magnetic resonance. Angew Chem Int Ed Engl 51:6904-7|
Showing the most recent 10 out of 15 publications