Multifunctionalized iron oxide nanoparticles for selective targeting of pancreatic cancer cells

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 6; pp. 1597 - 1605
• Main Authors: Trabulo, Sara, Aires, Antonio, Aicher, Alexandra, Heeschen, Christopher, Cortajarena, Aitziber L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2017
• Subjects: Active targeting; adenocarcinoma; adverse effects; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; CD47; CD47 Antigen - immunology; CD47 Antigen - metabolism; Cell Survival - drug effects; Controlled drug release; Deoxycytidine - analogs & derivatives; Deoxycytidine - chemistry; Deoxycytidine - metabolism; Deoxycytidine - pharmacology; Drug Carriers; Drug Compounding; drug therapy; drugs; Gemcitabine; Humans; iron oxides; Magnetic nanoparticles; Magnetics - methods; Magnetite Nanoparticles - chemistry; metastasis; monoclonal antibodies; Multifunctionalization; Nanocarriers; Nanomedicine; Nanomedicine - methods; nanoparticles; neoplasm cells; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; pancreas; Pancreatic cancer; pancreatic neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; solubility; stem cells; Surface Properties; Tumor Cells, Cultured; Controlled drug release; Gemcitabine; Pancreatic cancer; Magnetic nanoparticles; Active targeting; Multifunctionalization; CD47; Nanocarriers; Nanomedicine
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.01.035

Nanomedicine nowadays offers novel solutions in cancer therapy by introducing multimodal treatments in one single formulation. In addition, nanoparticles act as nanocarriers changing the solubility, biodistribution and efficiency of the therapeutic molecules, thus generating more efficient treatments and reducing their side effects. To apply these novel therapeutic approaches, efforts are focused on the multi-functionalization of the nanoparticles and will open up new avenues to advanced combinational therapies. Pancreatic ductal adenocarcinoma (PDAC) is a cancer with unmet medical needs. Abundant expression of the anti-phagocytosis signal CD47 has also been observed on pancreatic cancer cells, in particular a subset of cancer stem cells (CSCs) responsible for resistance to standard therapy and metastatic potential. CD47 receptor is found on pancreatic cancer and highly expressed on CSCs, but not on normal pancreas. Inhibiting CD47 using monoclonal antibodies has been shown as an effective strategy to treat PDAC in vivo. However, CD47 inhibition effectively slowed tumor growth only in combination with Gemcitabine or Abraxane. In this work, we present the generation of multifunctionalized iron oxide magnetic nanoparticles (MNPs) that include the anti-CD47 antibody and the chemotherapeutic drug Gemcitabine in a single formulation. We demonstrate the in vitro efficacy of the formulation against CD47-positive pancreatic cancer cells. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. [Display omitted] •Multifunctional magnetic nanoparticles including therapeutic antibodies and drugs•Controlled drug release system for selective treatment of pancreatic cancer cells•Targeting CD47, a pancreatic cancer stem cell biomarker•Effective targeting of functionalized MNPs to CD47-positive pancreatic cancer cells•Efficient induction of apoptosis by the CD47 antibody and the cytotoxicity of the drug