title: Synthesis, characterization and theranostic evaluation of Indium-111 labeled multifunctional superparamagnetic iron oxide nanoparticles.
abstract: Indium-111 labeled, Trastuzumab-Doxorubicin Conjugated, and APTES-PEG coated magnetic nanoparticles were designed for tumor targeting, drug delivery, controlled drug release, and dual-modal tumor imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by thermal decomposition method to obtain narrow size particles. To increase SPIONs circulation time in blood and decrease its cytotoxicity in healthy tissues, SPIONs surface was modified with 3-Aminopropyltriethoxy Silane (APTES) and then were functionalized with N-Hydroxysuccinimide (NHS) ester of Polyethylene Glycol Maleimide (NHS-PEG-Mal) to conjugate with thiolated 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA) bifunctional chelator (BFC) and Trastuzumab antibody. In order to tumor SPECT/MR imaging, SPIONs were labeled with Indium-111 (T1/2=2.80d). NHS ester of monoethyl malonate (MEM-NHS) was used for conjugation of Doxorubicin (DOX) chemotherapeutic agent onto SPIONs surface. Mono-Ethyl Malonate allows DOX molecules to be attached to SPIONs via pH-sensitive hydrazone bonds which lead to controlled drug release in tumor region. Active and passive tumor targeting were achieved through incorporated anti-HER2 (Trastuzumab) antibody and EPR effect of solid tumors for nanoparticles respectively. In addition to in vitro assessments of modified SPIONs in SKBR3 cell lines, their theranostic effects were evaluated in HER2 + breast tumor bearing BALB/c mice via biodistribution study, dual-modal molecular imaging and tumor diameter measurements.
authors.affiliation: AmirKabir University of Technology, Energy Engineering and Physics Faculty. Electronic address: hzolata@aut.ac.ir.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Zolata
authors.affiliation: Shahid Beheshti university of Tehran, Radiation Application Department. Electronic address: fabbasi@sbu.ac.ir.
authors.forename: Fereydoun
authors.initials: F
authors.lastname: Abbasi Davani
authors.affiliation: AmirKabir University of Technology, Energy Engineering and Physics Faculty.
authors.forename: Hossein
authors.initials: H
authors.lastname: Afarideh
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004317:Doxorubicin / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D005290:Ferric Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry; D011437:Propylamines; D012821:Silanes / Q000737:chemistry; D013388:Succinimides / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005290:Ferric Compounds; D007205:Indium Radioisotopes; D011437:Propylamines; D012821:Silanes; D013388:Succinimides; C000499:ferric oxide; D011092:Polyethylene Glycols; D004317:Doxorubicin; C477625:amino-propyl-triethoxysilane; C001426:N-hydroxysuccinimide; D000068878:Trastuzumab
keywords: Doxorubicin; Indium-111; SPECT/MR imaging; Superparamagnetic iron oxide nanoparticles; Trastuzumab