Multifunctionalized iron oxide nanoparticles for selective targeting of pancreatic cancer cells.
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.
Stem Cells & Cancer Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Centre for Stem Cells in Cancer & Ageing, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK.
Sara
S
Trabulo
CIC BiomaGUNE, Parque Tecnológico de San Sebastián, Paseo Miramón 182, Donostia-San Sebastián 20009, Spain; IMDEA Nanociencia and Nanobiotechnology Unit associated to Centro Nacional de Biotecnología (CNB-CSIC), Campus Universitario de Cantoblanco, Madrid 28049, Spain.
Antonio
A
Aires
Stem Cells & Cancer Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Alexandra
A
Aicher
Stem Cells & Cancer Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Centre for Stem Cells in Cancer & Ageing, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK. Electronic address: c.heeschen@qmul.ac.uk.
Christopher
C
Heeschen
CIC BiomaGUNE, Parque Tecnológico de San Sebastián, Paseo Miramón 182, Donostia-San Sebastián 20009, Spain; IMDEA Nanociencia and Nanobiotechnology Unit associated to Centro Nacional de Biotecnología (CNB-CSIC), Campus Universitario de Cantoblanco, Madrid 28049, Spain; Ikerbasque, Basque Foundation for Science, Mª Díaz de Haro 3, 48013 Bilbao, Spain. Electronic address: alcortajarena@cicbiomagune.es.
Aitziber L
AL
Cortajarena
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051928:CD47 Antigen / Q000276:immunology / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D008280:Magnetics / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D050997:Nanomedicine / Q000379:methods*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013499:Surface Properties; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051928:CD47 Antigen; C497894:CD47 protein, human; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D003841:Deoxycytidine; D000093542:Gemcitabine
Active targeting; CD47; Controlled drug release; Gemcitabine; Magnetic nanoparticles; Multifunctionalization; Nanocarriers; Nanomedicine; Pancreatic cancer