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omid c farokhzad

Giulio Caracciolo, Omid C Farokhzad, Morteza Mahmoudi
Despite the advances in biomedical applications of nanoparticle (NP) and numerous publications, few NPs have made it to clinical trials and even fewer have reached clinical practice. This wide gap between bench discoveries and clinical applications is mainly because of our limited understanding of the biological identity of NPs. In physiological environments, NPs are coated by a 'protein corona' (PC), critically affecting physiological and therapeutic responses. To date, nearly all studies attempting to characterize the PC have been conducted in vitro...
September 20, 2016: Trends in Biotechnology
Bruno A Cisterna, Nazila Kamaly, Won Il Choi, Ali Tavakkoli, Omid C Farokhzad, Cristian Vilos
Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could take advantage of differentially expressed molecules on the surface of tumor cells, providing effective release of cytotoxic drugs. Several efforts have recently reported the use of diverse molecules as ligands on the surface of nanoparticles to interact with the tumor cells, enabling the effective delivery of antitumor agents...
September 2016: Nanomedicine
Yanlan Liu, Viswanath Gunda, Xi Zhu, Xiaoding Xu, Jun Wu, Diana Askhatova, Omid C Farokhzad, Sareh Parangi, Jinjun Shi
Anaplastic thyroid cancer (ATC), one of the most aggressive solid tumors, is characterized by rapid tumor growth and severe metastasis to other organs. Owing to the lack of effective treatment options, ATC has a mortality rate of ∼100% and median survival of less than 5 months. RNAi nanotechnology represents a promising strategy for cancer therapy through nanoparticle (NP) -mediated delivery of RNAi agents (e.g., siRNA) to solid tumors for specific silencing of target genes driving growth and/or metastasis...
July 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yuan Xue, Xiaoyang Xu, Xue-Qing Zhang, Omid C Farokhzad, Robert Langer
The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature...
May 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
Xiaoding Xu, Jun Wu, Yanlan Liu, Mikyung Yu, Lili Zhao, Xi Zhu, Sushant Bhasin, Qing Li, Emily Ha, Jinjun Shi, Omid C Farokhzad
RNA interference (RNAi) gene silencing technologies have shown significant potential for treating various diseases, including cancer. However, clinical success in cancer therapy remains elusive, mainly owing to suboptimal in vivo delivery of RNAi therapeutics such as small interference RNA (siRNA) to tumors. Herein, we developed a library of polymers that respond to a narrow pH change (ultra-pH-responsive), and demonstrated the utility of these materials in targeted and deep tumor-penetrating nanoparticle (NP) for in vivo RNAi...
June 13, 2016: Angewandte Chemie
Nazila Kamaly, Gabrielle Fredman, Jhalique Jane R Fojas, Manikandan Subramanian, Won Ii Choi, Katherine Zepeda, Cristian Vilos, Mikyung Yu, Suresh Gadde, Jun Wu, Jaclyn Milton, Renata Carvalho Leitao, Livia Rosa Fernandes, Moaraj Hasan, Huayi Gao, Vance Nguyen, Jordan Harris, Ira Tabas, Omid C Farokhzad
Inflammation is an essential protective biological response involving a coordinated cascade of signals between cytokines and immune signaling molecules that facilitate return to tissue homeostasis after acute injury or infection. However, inflammation is not effectively resolved in chronic inflammatory diseases such as atherosclerosis and can lead to tissue damage and exacerbation of the underlying condition. Therapeutics that dampen inflammation and enhance resolution are currently of considerable interest, in particular those that temper inflammation with minimal host collateral damage...
May 24, 2016: ACS Nano
Bomy Lee Chung, Michael J Toth, Nazila Kamaly, Yoshitaka J Sei, Jacob Becraft, Willem J M Mulder, Zahi A Fayad, Omid C Farokhzad, YongTae Kim, Robert Langer
The endothelium lines the internal surfaces of blood and lymphatic vessels and has a critical role in maintaining homeostasis. Endothelial dysfunction is involved in the pathology of many diseases and conditions, including disorders such as diabetes, cardiovascular diseases, and cancer. Given this common etiology in a range of diseases, medicines targeting an impaired endothelium can strengthen the arsenal of therapeutics. Nanomedicine - the application of nanotechnology to healthcare - presents novel opportunities and potential for the treatment of diseases associated with an impaired endothelium...
December 1, 2015: Nano Today
Nazila Kamaly, Basit Yameen, Jun Wu, Omid C Farokhzad
No abstract text is available yet for this article.
February 24, 2016: Chemical Reviews
Xi Zhu, Jun Wu, Wei Shan, Wei Tao, Lili Zhao, Jong-Min Lim, Mathew D'Ortenzio, Rohit Karnik, Yuan Huang, Jinjun Shi, Omid C Farokhzad
Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e...
March 1, 2016: Angewandte Chemie
Miles A Miller, Suresh Gadde, Christina Pfirschke, Camilla Engblom, Melissa M Sprachman, Rainer H Kohler, Katherine S Yang, Ashley M Laughney, Gregory Wojtkiewicz, Nazila Kamaly, Sushma Bhonagiri, Mikael J Pittet, Omid C Farokhzad, Ralph Weissleder
Therapeutic nanoparticles (TNPs) have shown heterogeneous responses in human clinical trials, raising questions of whether imaging should be used to identify patients with a higher likelihood of NP accumulation and thus therapeutic response. Despite extensive debate about the enhanced permeability and retention (EPR) effect in tumors, it is increasingly clear that EPR is extremely variable; yet, little experimental data exist to predict the clinical utility of EPR and its influence on TNP efficacy. We hypothesized that a 30-nm magnetic NP (MNP) in clinical use could predict colocalization of TNPs by magnetic resonance imaging (MRI)...
November 18, 2015: Science Translational Medicine
Mikyung Yu, Jun Wu, Jinjun Shi, Omid C Farokhzad
Protein-based therapeutics have made a significant impact in the treatment of a variety of important human diseases. However, given their intrinsically vulnerable structure and susceptibility to enzymatic degradation, many therapeutic proteins such as enzymes, growth factors, hormones, and cytokines suffer from poor physicochemical/biological stability and immunogenicity that may limit their potential benefits, and in some cases limit their utility. Furthermore, when protein therapeutics are developed for intracellular targets, their internalization and biological activity may be limited by inefficient membrane permeability and/or endosomal escape...
October 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Omid C Farokhzad
No abstract text is available yet for this article.
October 1, 2015: Nature
Basit Yameen, Cristian Vilos, Won Il Choi, Andrew Whyte, Jining Huang, Lori Pollit, Omid C Farokhzad
The remarkably high intracellular concentration of reducing agents is an excellent endogenous stimulus for designing nanocarriers programmed for intracellular delivery of therapeutic agents. However, despite their excellent biodegradability profiles, aliphatic polyesters that are fully degradable in response to the intracellular reducing environment are rare. Herein, a reduction-responsive drug delivery nanocarrier derived from a linear polyester bearing disulfide bonds is reported. The reduction-responsive polyester is synthesized via a convenient polycondensation process...
August 3, 2015: Chemistry: a European Journal
Jun Wu, Lili Zhao, Xiaoding Xu, Nicolas Bertrand, Won Ii Choi, Basit Yameen, Jinjun Shi, Vishva Shah, Matthew Mulvale, James L MacLean, Omid C Farokhzad
Selective tumor targeting and drug delivery are critical for cancer treatment. Stimulus-sensitive nanoparticle (NP) systems have been designed to specifically respond to significant abnormalities in the tumor microenvironment, which could dramatically improve therapeutic performance in terms of enhanced efficiency, targetability, and reduced side-effects. We report the development of a novel L-cysteine-based poly (disulfide amide) (Cys-PDSA) family for fabricating redox-triggered NPs, with high hydrophobic drug loading capacity (up to 25 wt% docetaxel) and tunable properties...
August 3, 2015: Angewandte Chemie
Georg Stary, Andrew Olive, Aleksandar F Radovic-Moreno, David Gondek, David Alvarez, Pamela A Basto, Mario Perro, Vladimir D Vrbanac, Andrew M Tager, Jinjun Shi, Jeremy A Yethon, Omid C Farokhzad, Robert Langer, Michael N Starnbach, Ulrich H von Andrian
Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ-producing CD4 T cells. By contrast, we report that mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-) dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b(-)CD103(+) DCs...
June 19, 2015: Science
Xi Zhu, Yingjie Xu, Luisa M Solis, Wei Tao, Liangzhe Wang, Carmen Behrens, Xiaoyang Xu, Lili Zhao, Danny Liu, Jun Wu, Ning Zhang, Ignacio I Wistuba, Omid C Farokhzad, Bruce R Zetter, Jinjun Shi
RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery...
June 23, 2015: Proceedings of the National Academy of Sciences of the United States of America
Phei Er Saw, Jinho Park, Eunbeol Lee, Sukyung Ahn, Jinju Lee, Hyungjun Kim, Jinjoo Kim, Minsuk Choi, Omid C Farokhzad, Sangyong Jon
Standardized poly(ethylene glycol)-modified (PEGylated) liposomes, which have been widely used in research as well as in pre-clinical and clinical studies, are typically constructed using PEG with a molecular weight of 2000 Da (PEG(2000)). Targeting ligands are also generally conjugated using various functionalized PEG(2000)). However, although standardized protocols have routinely used PEG(2000), it is not because this molecular weight PEG has been optimized to enhance tumor uptake of nanoparticles. Herein, we investigated the effect of various PEG lipid pairings--that is, PEG lipids for targeting-ligand conjugation and PEG lipids for achieving 'stealth' function--on in vitro cancer cell- and in vivo tumor-targeting efficacy...
2015: Theranostics
Eric M Pridgen, Frank Alexis, Omid C Farokhzad
INTRODUCTION: Many therapeutics are limited to parenteral administration. Oral administration is a desirable alternative because of the convenience and increased compliance by patients, especially for chronic diseases that require frequent administration. Polymeric nanoparticles (NPs) are one technology being developed to enable clinically feasible oral delivery. AREAS COVERED: This review discusses the challenges associated with oral delivery. Strategies used to overcome gastrointestinal (GI) barriers using polymeric NPs will be considered, including mucoadhesive biomaterials and targeting of NPs to transcytosis pathways associated with M cells and enterocytes...
2015: Expert Opinion on Drug Delivery
Giovanna Leoni, Philipp-Alexander Neumann, Nazila Kamaly, Miguel Quiros, Hikaru Nishio, Hefin R Jones, Ronen Sumagin, Roland S Hilgarth, Ashfaqul Alam, Gabrielle Fredman, Ioannis Argyris, Emile Rijcken, Dennis Kusters, Chris Reutelingsperger, Mauro Perretti, Charles A Parkos, Omid C Farokhzad, Andrew S Neish, Asma Nusrat
Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits...
March 2, 2015: Journal of Clinical Investigation
Roberto A Maldonado, Robert A LaMothe, Joseph D Ferrari, Ai-Hong Zhang, Robert J Rossi, Pallavi N Kolte, Aaron P Griset, Conlin O'Neil, David H Altreuter, Erica Browning, Lloyd Johnston, Omid C Farokhzad, Robert Langer, David W Scott, Ulrich H von Andrian, Takashi Kei Kishimoto
Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists...
January 13, 2015: Proceedings of the National Academy of Sciences of the United States of America
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