title: Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy.
abstract: Nanoparticles with combined diagnostic and therapeutic functions are promising tools for cancer diagnosis and treatment. Here, we demonstrate a theranostic nanoparticle that integrates an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile supramolecular self-assembly synthesis, where the anti-cancer drug gemcitabine-5'-monophosphate (a phosphorylated active metabolite of the anti-cancer drug gemcitabine) was used to coordinate with Gd(III) to self-assemble into theranostic nanoparticles. The formulation exhibits a strong T1 contrast signal for magnetic resonance imaging of tumors in vivo, with enhanced retention time. Furthermore, the nanoparticles did not require other inert nanocarriers or excipients and thus had an exceptionally high drug loading (55 wt%), resulting in the inhibition of MDA-MB-231 tumor growth in mice.
  
  
  CONCLUSIONS
  Recent advances in nanoparticle-based drug delivery systems have spurred the development of "theranostic" multifunctional nanoparticles, which combine therapeutic and diagnostic functionalities in a single formulation. Developing simple and efficient synthetic strategies for the construction of nanotheranostics with high drug loading remains a challenge. Here, we demonstrate a theranostic nanoparticle that integrates high loadings of an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile synthesis. The nanoparticles were better T1 contrast agents than currently used Gd-DTPA and had prolonged retention in tumor. Moreover they exhibited enhanced in vivo antitumor activity compared to free drug in a breast cancer xenograft mouse model. The strategy provides a scalable way to fabricate nanoparticles that enables enhancement of both therapeutic and diagnostic capabilities.
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Lele
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Tong
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, United States. Electronic address: daniel.kohane@childrens.harvard.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012996:Solutions; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D012996:Solutions; D003841:Deoxycytidine; D005682:Gadolinium; D000093542:Gemcitabine
keywords: Cancer theranostics; Drug delivery; Gemcitabine monophosphate; Magnetic resonance imaging; Supramolecular nanoparticle
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