title: Multi-functional nanoparticles as theranostic agents for the treatment & imaging of pancreatic cancer.
abstract: Theranostics has received considerable attention since both therapy and imaging modalities can be integrated into a single nanocarrier. In this study, fluorescent iron oxide (FIO) nanoparticles and gemcitabine (G) encapsulated poly(lactide-co-glycolide) (PLGA) nanospheres (PGFIO) conjugated with human epidermal growth factor receptor 2, (HER-2) antibody (HER-PGFIO) were prepared and characterized. HER-PGFIO showed the magnetic moment of 10emu/g, relaxivity (r2) of 773mM-1s-1and specific absorption rate (SAR) of 183W/g. HER-PGFIO showed a sustained release of gemcitabine for 11days in PBS (pH 7.4). In vitro cytotoxicity evaluation of HER-PGFIO in 3D MIAPaCa-2 cultures showed 50% inhibitory concentration (IC50) of 0.11mg/mL. Subcutaneous tumor xenografts of MIAPaCa-2 in SCID mice were developed and the tumor regression study at the end of 30days showed significant tumor regression (86±3%) in the HER-PGFIO with magnetic hyperthermia (MHT) treatment group compared to control group. In vivo MRI imaging showed the enhanced contrast in HER-PGFIO+MHT treated group compared to control. HER-PGFIO showed significant tumor regression and enhanced MRI in treatment groups, which could be an effective nanocarrier system for the treatment of pancreatic cancer.
  
  
  
  Combination therapies are best suitable to treat pancreatic cancer. Theranostics are the next generation therapeutics with both imaging and treatment agents encapsulated in a single nanocarrier. The novelty of the present work is the development of targeted nanocarrier that provides chemotherapy, thermotherapy and MRI imaging properties. The present work is the next step in developing the nanocarriers for pancreatic cancer treatment. Different treatment modalities embedding into a single nanocarrier is the biggest challenge that was achieved without compromising the functionality of each other. The surface modification of polymeric nanocarriers for antibody binding and their multifunctional abilities will appeal to wider audience.
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: L R
authors.initials: LR
authors.lastname: Jaidev
authors.affiliation: Central Animal House Facility, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: David Raj
authors.initials: DR
authors.lastname: Chellappan
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Dhiraj Vasanth
authors.initials: DV
authors.lastname: Bhavsar
authors.affiliation: Department of Radiology, KAPVG Medical College, Trichy 620001, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Ranganathan
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Banudevi
authors.initials: B
authors.lastname: Sivanantham
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Subramanian
authors.affiliation: Department of NMR & MRI Facility, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Department of NMR & MRI Facility, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.
authors.forename: Narnamangalam R
authors.initials: NR
authors.lastname: Jagannathan
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Uma Maheswari
authors.initials: UM
authors.lastname: Krishnan
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India. Electronic address: swami@sastra.edu.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Sethuraman
mesh_terms: D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D004705:Endocytosis / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry; D005453:Fluorescence; D006801:Humans; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012074:Remission Induction; D000068936:Theranostic Nanomedicine; D047368:Tumor Burden / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D004337:Drug Carriers; D005290:Ferric Compounds; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018719:Erb-b2 Receptor Tyrosine Kinases; D000093542:Gemcitabine; C000499:ferric oxide
keywords: 3D in vitro; Alginate sponge; Fluorescent iron oxide nanoparticles; Gemcitabine; MR imaging; Multifunctional nanoparticles; Pancreatic cancer; Theranostics