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An Aptamer–Doxorubicin Physical Conjugate as a Novel Targeted Drug-Delivery Platform
Bagalkot, Vaishali,Farokhzad, Omid C.,Langer, Robert,Jon, Sangyong WILEY-VCH Verlag 2006 Angewandte Chemie Vol.45 No.48
<B>Graphic Abstract</B> <P>Trojan aptamer: A novel strategy for targeted drug delivery to cancer cells was developed through the formation of a physical conjugate (see scheme) between doxorubicin (Dox) and the A10 RNA aptamer that binds to the prostate-specific membrane antigen (PSMA). The aptamer–Dox conjugate could efficiently bind to PSMA-expressing cells, thereby resulting in its uptake and the intracellular release of Dox. <img src='wiley_img/14337851-2006-45-48-ANIE200602251-content.gif' alt='wiley_img/14337851-2006-45-48-ANIE200602251-content'> </P>
Gold, poly(beta-amino ester) nanoparticles for small interfering RNA delivery.
Lee, Jae-Seung,Green, Jordan J,Love, Kevin T,Sunshine, Joel,Langer, Robert,Anderson, Daniel G American Chemical Society 2009 NANO LETTERS Vol.9 No.6
<P>The safe and effective delivery of RNA therapeutics remains the major barrier to their broad clinical application. Here we develop a new nanoparticulate delivery system based on inorganic particles and biodegradable polycations. First, gold nanoparticles were modified with the hydrophilic polymer poly(ethylene glycol) (PEG), and then small interfering RNA (siRNA) was conjugated to the nanoparticles via biodegradable disulfide linkages, with approximately 30 strands of siRNA per nanoparticle. The particles were then coated with a library of end-modified poly(beta-amino ester)s (PBAEs), previously identified as capable of facilitating intracellular DNA delivery. Nanoparticulate formulations developed here facilitate high levels of in vitro siRNA delivery, facilitating delivery as good or better than the commercially available lipid reagent, Lipofectamine 2000.</P>
Co-Delivery of Hydrophobic and Hydrophilic Drugs from Nanoparticle–Aptamer Bioconjugates
Zhang, Liangfang,Radovic-Moreno, Aleksandar F.,Alexis, Frank,Gu, Frank X.,Basto, Pamela A.,Bagalkot, Vaishali,Jon, Sangyong,Langer, Robert S.,Farokhzad, Omid C. WILEY-VCH Verlag 2007 ChemMedChem Vol.2 No.9
<B>Graphic Abstract</B> <P>Herein we report a novel targeted drug delivery system consisting of nanoparticle–aptamer bioconjugates, which can carry both hydrophobic and hydrophilic chemotherapeutic drugs simultaneously, and deliver them selectively in a targeted and temporally distinct manner. This work provides a robust platform for targeted co-delivery of chemotherapeutic agents with the hope of both leveraging the synergistic effects of multiple drugs and also potentially suppressing the likelihood of drug resistance by the treated tissues. <img src='wiley_img/18607179-2007-2-9-CMDC200700121-content.gif' alt='wiley_img/18607179-2007-2-9-CMDC200700121-content'> </P>
One‐Step Multipurpose Surface Functionalization by Adhesive Catecholamine
Kang, Sung Min,Hwang, Nathaniel S.,Yeom, Jihyeon,Park, Sung Young,Messersmith, Phillip B.,Choi, Insung S.,Langer, Robert,Anderson, Daniel G.,Lee, Haeshin WILEY‐VCH Verlag 2012 Advanced functional materials Vol.22 No.14
<P><B>Abstract</B></P><P>Surface modification is one of the most important techniques in modern science and engineering. The facile introduction of a wide variety of desired properties onto virtually any material surface is an ultimate goal in surface chemistry. To achieve this goal, the incorporation of structurally diverse molecules onto any material surface is an essential capability for ideal surface modification. Here, a general strategy for surface modification is presented in which many diverse surfaces can be functionalized by immobilizing a wide variety of molecules. This strategy functionalizes surfaces by a one‐step immersion of substrates in a one‐pot mixture of a molecule and a catecholamine surface modification agent. This one‐step procedure for surface modification represents a standard protocol to control interfacial properties.</P>
A Novel Family of Biodegradable Poly(ester amide) Elastomers
Cheng, Hao,Hill, Paulina S.,Siegwart, Daniel J.,Vacanti, Nathaniel,Lytton‐,Jean, Abigail K. R.,Cho, Seung‐,Woo,Ye, Anne,Langer, Robert,Anderson, Daniel G. WILEY‐VCH Verlag 2011 ADVANCED MATERIALS Vol.23 No.12
<P><B>Biodegradable elastomeric materials</B> have particular utility in tissue engineering applications because their compliance under force closely resembles the elastic nature of many human tissues. A family of biodegradable poly(ester amide) elastomers were developed, with excellent elasticity under hydrated conditions, good in vivo biocompatibility and a slow degradation rate. This study sheds light on the structure‐property relationship behind designing biodegradable elastomeric materials. </P>
Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c–SIRT2 axis
Cha, Young,Han, Min-Joon,Cha, Hyuk-Jin,Zoldan, Janet,Burkart, Alison,Jung, Jin Hyuk,Jang, Yongwoo,Kim, Chun-Hyung,Jeong, Ho-Chang,Kim, Byung-Gyu,Langer, Robert,Kahn, C. Ronald,Guarente, Leonard,Kim, K Nature Publishing Group 2017 NATURE CELL BIOLOGY Vol. No.
<P>A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2 overexpression in hPSCs significantly affected energy metabolism, altering stem cell functions such as pluripotent differentiation properties. Taken together, our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function.</P>
Chung, Hyun Jung,Lee, Haeshin,Bae, Ki Hyun,Lee, Yuhan,Park, Jongnam,Cho, Seung-Woo,Hwang, Jin Young,Park, Hyunwook,Langer, Robert,Anderson, Daniel,Park, Tae Gwan American Chemical Society 2011 ACS NANO Vol.5 No.6
<P>Currently available methods to stably disperse iron oxide nanoparticles (IONPs) in aqueous solution need to be improved due to potential aggregation, reduction of superparamagnetism, and the use of toxic reagents. Herein, we present a facile strategy for aqueous transfer and dispersion of organic-synthesized IONPs using only polyethylene glycol (PEG), a biocompatible polymer. A library of PEG derivatives was screened, and it was determined that amine-functionalized six-armed PEG, 6(PEG-NH<SUB>2</SUB>), was the most effective dispersion agent. The 6(PEG-NH<SUB>2</SUB>)-modified IONPs (IONP-6PEG) were stable after extensive washing, exhibited high superparamagnetism, and could be used as a platform material for secondary surface functionalization with bioactive polymers. IONP-6PEG biofunctionalized with hyaluronic acid (IONP-6PEG-HA) was shown to specifically label mesenchymal stem cells and demonstrate MR contrast potential with high <I>r</I><SUB>2</SUB> relaxivity (442.7 s<SUP>–1</SUP>mM<SUP>–1</SUP>) compared to the commercially available Feridex (182.1 s<SUP>–1</SUP>mM<SUP>–1</SUP>).</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2011/ancac3.2011.5.issue-6/nn201198f/production/images/medium/nn-2011-01198f_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn201198f'>ACS Electronic Supporting Info</A></P>