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

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• 作者：L.R. Jaidev^a ; David Raj Chellappan^b ; Dhiraj Vasanth Bhavsar^a ; Ravi Ranganathan^c ; Banudevi Sivanantham^a ; Anuradha Subramanian^a ; Uma Sharma^d ; Narnamangalam R. Jagannathan^d ; Uma Maheswari Krishnan^a ; Swaminathan Sethuraman^a ; ^{swami@sastra.edu}
• 关键词：Theranostics ; Fluorescent iron oxide nanoparticles ; 3D in vitro ; Multifunctional nanoparticles ; Alginate sponge ; Gemcitabine ; Pancreatic cancer ; MR imaging
• 刊名：Acta Biomaterialia
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：49
• 期：Complete
• 页码：422-433
• 全文大小：3829 K
• 卷排序：49

文摘

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 SignificanceCombination 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.