Multivalent niacin nanoconjugates for delivery to cytoplasmic lipid droplets

作者: Anjali Sharma , Armen Khatchadourian , Kunal Khanna , Rishi Sharma , Ashok Kakkar

DOI: 10.1016/J.BIOMATERIALS.2010.10.025

关键词: BODIPYLipid dropletMaterials scienceDrug deliveryCytoplasmClick chemistryNanoconjugatesNiacinNanocarriersBiochemistry

摘要: We report here the design, synthesis, and properties, of multifunctional niacin nanoconjugates based on dendritic, miktoarm linear backbone nanocarriers, using “click” chemistry. The conjugates were in this instance used to deliver therapeutic agent lipid droplets. desired combination niacin, a lipophilic fluorescent dye (BODIPY), polyethylene glycol (PEG), was achieved by covalently linking agents selected carrier. nanocarriers containing BODIPY found almost exclusively within cytoplasmic droplets cells study (living hepatocytes microglia), whereas trifunctional carrier PEG partially localized these organelles but also elsewhere compartment. Spectrofluorometric analyses, confocal microscopy fluorescence cell sorting revealed different rates extent conjugate(s) internalization two types. Even micromolar concentrations internalized did not cause significant death or mitochondrial functional impairment, suggesting that they are suitable candidate nanostructures for droplet imaging targeting drugs cellular organelles. These studies provide an efficient easy way synthesize click chemistry, applicable synthesis related their use organelles, including

参考文章(46)
John A Pieper, Understanding Niacin Formulations The American Journal of Managed Care. ,vol. 8, ,(2002)
Radoslav Savic, Laibin Luo, Adi Eisenberg, Dusica Maysinger, Micellar Nanocontainers Distribute to Defined Cytoplasmic Organelles Science. ,vol. 300, pp. 615- 618 ,(2003) , 10.1126/SCIENCE.1078192
James McKenney, Niacin for dyslipidemia: Considerations in product selection American Journal of Health-system Pharmacy. ,vol. 60, pp. 995- 1005 ,(2003) , 10.1093/AJHP/60.10.995
Marion Csiky, Marie Catherine Suchánková, Rolf M. Nüsing, Alexandra Moers, Klaus Pfeffer, Stefan Offermanns, Zoltán Benyó, Andreas Gille, Jukka Kero, GPR109A (PUMA-G/HM74A) mediates nicotinic acid–induced flushing Journal of Clinical Investigation. ,vol. 115, pp. 3634- 3640 ,(2005) , 10.1172/JCI23626
Dusica Maysinger, Maik Behrendt, Mélanie Lalancette-Hébert, Jasna Kriz, Real-Time Imaging of Astrocyte Response to Quantum Dots:  In Vivo Screening Model System for Biocompatibility of Nanoparticles Nano Letters. ,vol. 7, pp. 2513- 2520 ,(2007) , 10.1021/NL071611T
Robert V. Farese, Tobias C. Walther, Lipid Droplets Finally Get a Little R-E-S-P-E-C-T Cell. ,vol. 139, pp. 855- 860 ,(2009) , 10.1016/J.CELL.2009.11.005
Cheol Soo Choi, David B. Savage, Ameya Kulkarni, Xing Xian Yu, Zhen-Xiang Liu, Katsutaro Morino, Sheene Kim, Alberto Distefano, Varman T. Samuel, Susanne Neschen, Dongyan Zhang, Amy Wang, Xian-Man Zhang, Mario Kahn, Gary W. Cline, Sanjay K. Pandey, John G. Geisler, Sanjay Bhanot, Brett P. Monia, Gerald I. Shulman, Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance Journal of Biological Chemistry. ,vol. 282, pp. 22678- 22688 ,(2007) , 10.1074/JBC.M704213200
Vaijinath S. Kamanna, Moti L. Kashyap, Mechanism of action of niacin on lipoprotein metabolism. Current Atherosclerosis Reports. ,vol. 2, pp. 36- 46 ,(2000) , 10.1007/S11883-000-0093-1
Hiroshi Maeda, Len W. Seymour, Yoichi Miyamoto, Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo. Bioconjugate Chemistry. ,vol. 3, pp. 351- 362 ,(1992) , 10.1021/BC00017A001
Shobha H. Ganji, S. Tavintharan, Daming Zhu, Yiding Xing, Vaijinath S. Kamanna, Moti L. Kashyap, Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. Journal of Lipid Research. ,vol. 45, pp. 1835- 1845 ,(2004) , 10.1194/JLR.M300403-JLR200