title: Manganese oxide and docetaxel co-loaded fluorescent polymer nanoparticles for dual modal imaging and chemotherapy of breast cancer.
abstract: Multifunctional nanoparticles (NPs) have found important applications in diagnosis, chemotherapy, and image-guided surgery of tumors. In this work, we have developed polymeric theranostic NPs (PTNPs) containing the anticancer drug docetaxel (DTX), a fluorescent dye, and magnetic manganese oxide (MnO) NPs for dual modal imaging and chemotherapy. PTNPs ~150 nm in diameter were synthesized by co-loading hydrophobic DTX and MnO NPs ~5 nm in diameter, into the matrix of a fluorescent dye-labeled amphiphilic polymer. The PTNPs enabled high loading efficiency and sustained in vitro release of DTX. Energy-dependent cellular uptake and extended cytoplasmic retention of the PTNPs in MDA-MB-231 human breast cancer cells were observed by fluorescence microscopy examination. DTX-loaded PTNPs exhibited higher cytotoxicity than free DTX with a 3 to 4.4-fold decrease in drug dose required for 50% cell growth inhibition. The hydrophilic backbone of the amphiphilic polymer improved the fluidity of PTNPs which enhanced the longitudinal relaxivity (r1) of loaded MnO NPs by 2.7-fold with r1=2.4mM(-1)s(-1). Whole body fluorescence imaging (FI) and magnetic resonance imaging (MRI) showed significant accumulation and prolonged retention of PTNPs in orthotopic MDA-MB-231 breast tumors. These results suggest that the new amphiphilic polymer-based PTNP system, able to simultaneously deliver a poorly soluble anticancer drug, enhance MRI contrast, and stain tumor tissue by fluorescence, is a good candidate for cancer theranostic applications.
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Electronic address: az.abbasi@utoronto.ca.
authors.forename: Azhar Z
authors.initials: AZ
authors.lastname: Abbasi
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Electronic address: preethy.prasad@utoronto.ca.
authors.forename: Preethy
authors.initials: P
authors.lastname: Prasad
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Electronic address: ping.cai@utoronto.ca.
authors.forename: Ping
authors.initials: P
authors.lastname: Cai
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Electronic address: chanson.he@utoronto.ca.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: He
authors.affiliation: STTARR Innovation Centre, Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada. Electronic address: warren.foltz@rmp.uhn.on.ca.
authors.forename: Warren D
authors.initials: WD
authors.lastname: Foltz
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Electronic address: ma.amini@utoronto.ca.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Amini
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Electronic address: claudia.gordijo@utoronto.ca.
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Gordijo
authors.affiliation: Ontario Cancer Institute, Division of Radiation Oncology, University of Toronto, Department of Medical Biophysics, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. Electronic address: rauth@uhnres.utoronto.ca.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Rauth
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Electronic address: xywu@phm.utoronto.ca.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D065546:Drug Liberation; D005260:Female; D005452:Fluoresceins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D010087:Oxides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017895:Manganese Compounds; D010087:Oxides; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; C030864:5-aminofluorescein; C027424:manganese oxide
keywords: Cancer; Drug delivery; Dual modal imaging; Manganese oxide; Multifunctional nanoparticles