1. Lipoproteins LDL versus HDL as nanocarriers to target either cancer cells or macrophages
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Lucile Dondaine, Carmen Garrido, Mathieu Moreau, Frédéric Lirussi, Romain Douhard, Samir Messaoudi, Christophe Ramseyer, Pierre-Simon Bellaye, Tatiana Lopez, Tarik Hadi, Sarah Foley, Laurent Lagrost, Lil Proukhnitzky, Thomas Gautier, Semen O. Yesylevskyy, Franck Denat, Fabrice Neiers, Antonin Schmitt, Maeva Wendremaire, Thibault Minervini, Bertrand Collin, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bourgogne Franche-Comté [COMUE] (UBFC), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institute of Metal Physics of the National Academy of Sciences of Ukraine, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-CY Cergy Paris Université (CY), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Messaoudi, Samir, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire Chrono-environnement (UMR 6249) (LCE), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Bourgogne (UB), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), and Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)
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0301 basic medicine ,medicine.medical_treatment ,cisplatin ,lcsh:Medicine ,heat shock protein inhibitor ,Cancer immunotherapy ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,Spectrum Analysis, Raman ,Mice ,Drug Delivery Systems ,0302 clinical medicine ,Chemistry ,selective cell targeting ,General Medicine ,3. Good health ,Lipoproteins, LDL ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,cancer therapy ,lipids (amino acids, peptides, and proteins) ,Colorectal Neoplasms ,Lipoproteins, HDL ,Research Article ,medicine.drug ,[CHIM.THER] Chemical Sciences/Medicinal Chemistry ,Lipoproteins ,Therapeutics ,Cell Line ,03 medical and health sciences ,Immune system ,In vivo ,Cell Line, Tumor ,medicine ,vectorization ,Animals ,Humans ,Cisplatin ,Macrophages ,lcsh:R ,Cancer ,medicine.disease ,Colorectal cancer ,In vitro ,030104 developmental biology ,Cancer cell ,Cancer research ,Nanocarriers ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
free open access article 31 p.; International audience; In this work, we have explored natural unmodified low- and high-density lipoproteins (LDL and HDL) as selective delivery vectors in colorectal cancer therapy. We show in vitro in cultured cells and in vivo (NanoSPECT/CT) in the CT-26 mice colorectal cancer model that LDLs are mainly taken up by cancer cells, while HDLs are preferentially taken up by macrophages. We loaded LDLs with cisplatin and HDLs with the heat shock protein-70 inhibitor AC1LINNC, turning them into a pair of “Trojan horses” delivering drugs selectively to their target cells as demonstrated in vitro in human colorectal cancer cells and macrophages, and in vivo. Coupling of the drugs to lipoproteins and stability was assessed by mass and raman spectrometry analysis. Cisplatin vectorized in LDLs led to better tumor growth suppression with strongly reduced adverse effects such as a renal or liver toxicity. AC1LINNC vectorized into HDLs induced a strong oxidative burst in macrophages and innate anti-cancer immune response. Cumulative anti-tumor effect was observed for both drug-loaded lipoproteins. Altogether, our data show that lipoproteins from patient’s blood can be used as natural nanocarriers allowing cell specific targeting, paving the way toward more efficient, safer and personalized use of chemo-and immunotherapeutic drugs in cancer
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- 2020