Multi-Modal Gold Nanoparticles for Simultaneous Lineage-Specific Targeted Delivery and Tracking of Chemotherapeutics

Au nanoparticles, along with other drug delivery technologies such as micellar and liposomal or polymeric encapsulations, and monoclonal antibody conjugation, have been intensively pursued as candidates to advance nanomedicine. Realizing multiple functionalities in one platform is an important prospect of nanomedicine. We have developed an amine-passivated Au nanoparticle drug delivery platform that allows for controlled payload release in specific cell lineage. Our approach is to use Au nanoparticles as intermediaries to which drug and targeting moieties are simultaneously attached using simple but different chemistries that permit controlled release of drug, while ensuring targeting functionality intact. To demonstrate this, we established robust and scalable synthesis of daunorubicin (DNR)-loaded Au nanoparticles functionalized with erythropoietin mimetic peptide (EMP). In essence, we use Au nanoparticles as a “linker” between drug molecules and EMP. We elucidate payload delivery to erythroid progenitors in murine bone marrow via flow cytometry and fluorescence microscopy. Exploiting the recovery of quenched DNR fluorescence upon release from Au nanoparticle surface as a reporter, cell lineage-targeted payload delivery is demonstrated. The drug-Au-EMP platform allows for versatile choice of drugs as well as targeting moieties, and could potentially improve therapeutic index in breadth of existing drugs.