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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>
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>
Mohammad Ali Rezvani,Farokhzad Mohammadi Zonoz 한국공업화학회 2015 Journal of Industrial and Engineering Chemistry Vol.22 No.-
[C16H33N(CH3)3]4H3SiV3W9O40 has been synthesized by reaction of Na10[a-SiW9O34] with sodiumvanadate and encapsulated by cetyltrimethyl ammonium. Then this organic–inorganic hybrid compoundcondensation with titanium tetraisopropoxide at 100 C via sol–gel method under oil-bath condition. [C16H33N(CH3)3]4H3SiV3W9O40-TiO2 was prepared. The materials characterized by IR, XRD, TEM andUV–vis techniques. This alkyl ammonium keggin- type nanoparticle be able to scavenge mercaptans andhydrogen sulfide (with high yield) in the presence of H2O2. This system provides a practical, convenientand efficient method for scavenging of sulfur compound in light and heavy crude oil.
Saw, Phei Er,Park, Jinho,Jon, Sangyong,Farokhzad, Omid C. Elsevier 2017 NANOMEDICINE Vol.13 No.2
<P><B>Abstract</B></P> <P>A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers. We constructed EDB-specific aptide (APT<SUB>EDB</SUB>)-conjugated liposome to simultaneously deliver siRNA(siMDR1) and Dox to drug-resistant breast cancer cells. APT<SUB>EDB</SUB>-LS(Dox,siMDR1) led to enhanced delivery of payloads into MCF7/ADR cells and showed significantly higher accumulation and retention in the tumors. While either APT<SUB>EDB</SUB>-LS(Dox) or APT<SUB>EDB</SUB>-LS(siMDR1) did not lead to appreciable tumor retardation in MCF7/ADR orthotropic model, APT<SUB>EDB</SUB>-LS(Dox,siMDR1) treatment resulted in significant reduction of the drug-resistant breast tumor. Taken together, this study provides a new strategy of drug delivery for drug-resistant cancer therapy.</P> <P><B>Graphical Abstract</B></P> <P>A novel multi-drug resistance cancer therapy – EDB targeting liposome simultaneously encapsulating MDR-1 siRNA and doxorubicin for targeted, co-delivery of drug for the treatment of drug resistant breast cancer.</P> <P>[DISPLAY OMISSION]</P>
HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy
Park, Jinho,Park, Seho,Kim, Sunghyun,Lee, In-Hyun,Saw, Phei Er,Lee, Kwangyeol,Kim, Yong-Chul,Kim, Young-Joon,Farokhzad, Omid C.,Jeong, Yong Yeon,Jon, Sangyong The Royal Society of Chemistry 2013 Journal of materials chemistry. B, Materials for b Vol.1 No.36