An Intein‐Mediated Site‐Specific Click Conjugation Strategy for Improved Tumor Targeting of Nanoparticle Systems
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Abstract
The ability to modify and directly target nanoparticulate carriers has greatly increased their applicability in diagnostic and therapeutic studies. Generally essential to the targeting of nanoparticles is the bioconjugation of targeting ligands to the agent's surface. While bioconjugation techniques have steadily improved in recent years, the field is still plagued with inefficient conjugations reactions and/or the lack of site‐specific coupling. To overcome these limitations, click chemistry and expressed protein ligation (EPL) are combined to produce a highly efficient, site‐specific reaction. This new EPL–click conjugation strategy is applied to create superparamagnetic iron oxide nanoparticles (SPIO) labeled with HER2/neu affibodies. These HER2‐SPIO nanoparticles prove to be highly potent and receptor‐specific in both in vitro cell studies and murine tumor models. Moreover, when EPL–click‐derived HER2‐SPIO are compared with SPIO that had been labeled with HER2 affibodies using other popular bioconjugation methods, they produce a statistically significant improvement in contrast enhancement upon cell binding. The EPL–click system is also successfully extended to other nanoparticle platforms (i.e., liposomes and dendrimers) highlighting the versatility of the approach.Keywords
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