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Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo
Farokhzad, O. C.,Cheng, J.,Teply, B. A.,Sherifi, I.,Jon, S.,Kantoff, P. W.,Richie, J. P.,Langer, R. Proceedings of the National Academy of Sciences 2006 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.103 No.16
<P>Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology. Using prostate cancer as a model, we report docetaxel (Dtxl)-encapsulated nanoparticles formulated with biocompatible and biodegradable poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) copolymer and surface functionalized with the A10 2'-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen (PSMA), a well characterized antigen expressed on the surface of prostate cancer cells. These Dtxl-encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-Apt) bind to the PSMA protein expressed on the surface of LNCaP prostate epithelial cells and get taken up by these cells resulting in significantly enhanced in vitro cellular toxicity as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP) (P < 0.0004). The Dtxl-NP-Apt bioconjugates also exhibit remarkable efficacy and reduced toxicity as measured by mean body weight loss (BWL) in vivo [body weight loss of 7.7 +/- 4% vs. 18 +/- 5% for Dtxl-NP-Apt vs. Dtxl-NP at nadir, respectively (mean +/- SD); n = 7]. After a single intratumoral injection of Dtxl-NP-Apt bioconjugates, complete tumor reduction was observed in five of seven LNCaP xenograft nude mice (initial tumor volume of approximately 300 mm3), and 100% of these animals survived our 109-day study. In contrast, two of seven mice in the Dtxl-NP group had complete tumor reduction with 109-day survivability of only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles without drug were similarly nonefficacious. This report demonstrates the potential utility of nanoparticle-aptamer bioconjugates for a therapeutic application.</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>
Observation of High-Aspect-Ratio Nanostructures Using Capillary Lithography
Suh, K. Y.,Choi, S.-J.,Baek, S. J.,Kim, T. W.,Langer, R. WILEY-VCH Verlag 2005 Advanced Materials Vol.17 No.5
<B>Graphic Abstract</B> <P>Several intriguing nanostructures, such as mushroom-like nanopillars, vertical nanopillars (see Figure), and nanospheres, are made using capillary lithography and a new, UV-curable mold consisting of polyurethane functionalized with an acrylate group. An aspect ratio as high as five is achieved for nanopillars 90 nm in diameter. <img src='wiley_img/09359648-2005-17-5-ADMA200401089-content.gif' alt='wiley_img/09359648-2005-17-5-ADMA200401089-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>