Multi-functional nanoparticles as theranostic agents for the treatment & imaging of pancreatic cancer

Autor: Narnamangalam R. Jagannathan, Banudevi Sivanantham, Swaminathan Sethuraman, Dhiraj Bhavsar, David Raj Chellappan, Ravi Ranganathan, Uma Sharma, Anuradha Subramanian, L.R. Jaidev, Uma Maheswari Krishnan
Rok vydání: 2017
Předmět:
Male
Receptor
ErbB-2
medicine.medical_treatment
Mice
SCID
02 engineering and technology
Deoxycytidine
Ferric Compounds
Biochemistry
Theranostic Nanomedicine
Mice
chemistry.chemical_compound
0302 clinical medicine
Polylactic Acid-Polyglycolic Acid Copolymer
Drug Carriers
Cell Death
Remission Induction
General Medicine
021001 nanoscience & nanotechnology
Magnetic Resonance Imaging
Endocytosis
Tumor Burden
PLGA
030220 oncology & carcinogenesis
0210 nano-technology
Biotechnology
medicine.drug
Materials science
Biomedical Engineering
Fluorescence
Biomaterials
Inhibitory Concentration 50
03 medical and health sciences
In vivo
Cell Line
Tumor
Pancreatic cancer
medicine
Animals
Humans
Lactic Acid
Molecular Biology
IC50
Chemotherapy
medicine.disease
Gemcitabine
Pancreatic Neoplasms
Magnetic hyperthermia
chemistry
NIH 3T3 Cells
Cancer research
Nanoparticles
Nanocarriers
Polyglycolic Acid
Biomedical engineering
Zdroj: Acta Biomaterialia. 49:422-433
ISSN: 1742-7061
DOI: 10.1016/j.actbio.2016.11.053
Popis: 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 10 emu/g, relaxivity (r2) of 773 mM−1 s−1 and specific absorption rate (SAR) of 183 W/g. HER-PGFIO showed a sustained release of gemcitabine for 11 days in PBS (pH 7.4). In vitro cytotoxicity evaluation of HER-PGFIO in 3D MIAPaCa-2 cultures showed 50% inhibitory concentration (IC50) of 0.11 mg/mL. Subcutaneous tumor xenografts of MIAPaCa-2 in SCID mice were developed and the tumor regression study at the end of 30 days 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. Statement of Significance 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.
Databáze: OpenAIRE
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