title: Design considerations for tumour-targeted nanoparticles.
abstract: Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5-10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: Wenhao
authors.initials: W
authors.lastname: Liu
authors.forename: Fangbing
authors.initials: F
authors.lastname: Liu
authors.forename: Khaled
authors.initials: K
authors.lastname: Nasr
authors.forename: Preeti
authors.initials: P
authors.lastname: Misra
authors.forename: Moungi G
authors.initials: MG
authors.lastname: Bawendi
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D019187:Cadmium Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D005453:Fluorescence; D043425:Glutamate Carboxypeptidase II / Q000032:analysis; D006801:Humans; D039564:Integrin alphaV / Q000032:analysis; D039661:Integrin beta3 / Q000032:analysis; D008297:Male; D008545:Melanoma / Q000175:diagnosis*; D051379:Mice; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D045663:Quantum Dots; D018036:Selenium Compounds / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000954:Antigens, Surface; D019187:Cadmium Compounds; D039564:Integrin alphaV; D039661:Integrin beta3; D018036:Selenium Compounds; C058667:cadmium selenide; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II