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Sunandini Chopra, Nicolas Bertrand, Jong-Min Lim, Amy Wang, Omid C Farokhzad, Rohit Karnik
Nanoparticle (NP) carriers provide new opportunities for controlled delivery of drugs, and have potential to address challenges such as effective oral delivery of insulin. However, due to the difficulty of efficiently loading insulin and other proteins inside polymeric NPs, their use has been mostly restricted to the encapsulation of small molecules. To better understand the processes involved in encapsulation of proteins in NPs, we study how buffer conditions, ionic chelation, and preparation methods influence insulin loading in poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) NPs...
March 21, 2017: ACS Applied Materials & Interfaces
Xiaoding Xu, Jun Wu, Yanlan Liu, Phei Er Saw, Wei Tao, Mikyung Yu, Harshal Zope, Michelle Si, Amanda Victorious, Jonathan Rasmussen, Dana Ayyash, Omid C Farokhzad, Jinjun Shi
With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular nonliver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery...
March 28, 2017: ACS Nano
Ali Khademhosseini, Warren W C Chan, Manish Chhowalla, Sharon C Glotzer, Yury Gogotsi, Jason H Hafner, Paula T Hammond, Mark C Hersam, Ali Javey, Cherie R Kagan, Nicholas A Kotov, Shuit-Tong Lee, Yan Li, Helmuth Möhwald, Paul A Mulvaney, Andre E Nel, Wolfgang J Parak, Reginald M Penner, Andrey L Rogach, Raymond E Schaak, Molly M Stevens, Andrew T S Wee, Jeffrey Brinker, Xiaoyuan Chen, Lifeng Chi, Michael Crommie, Cees Dekker, Omid Farokhzad, Christoph Gerber, David S Ginger, Darrell J Irvine, Laura L Kiessling, Kostas Kostarelos, Christy Landes, Takhee Lee, Graham J Leggett, Xing-Jie Liang, Luis Liz-Marzán, Jill Millstone, Teri W Odom, Aydogan Ozcan, Maurizio Prato, C N R Rao, Michael J Sailor, Emily Weiss, Paul S Weiss
No abstract text is available yet for this article.
February 28, 2017: ACS Nano
Phei Er Saw, Mikyung Yu, Minsuk Choi, Eunbeol Lee, Sangyong Jon, Omid C Farokhzad
Although PEGylated liposomes (PEG-LS) have been intensively studied as drug-delivery vehicles, the rigidity and the hydrophilic PEG corona of liposomal membranes often limits cellular uptake, resulting in insufficient drug delivery to target cells. Thus, it is necessary to develop a new type of lipid-based self-assembled nanoparticles capable of enhanced cellular uptake, tissue penetration, and drug release than conventional PEGylated liposomes. Herein, we describe a simple modification of bicellar formulation in which the addition of a PEGylated phospholipid produced a dramatic physicochemical change in morphology, i...
January 31, 2017: Biomaterials
Claudia Corbo, Roberto Molinaro, Mateen Tabatabaei, Omid C Farokhzad, Morteza Mahmoudi
It is now well understood that once in contact with biological fluids, nanoscale objects lose their original identity and acquire a new biological character, referred to as a protein corona. The protein corona changes many of the physicochemical properties of nanoparticles, including size, surface charge, and aggregation state. These changes, in turn, affect the biological fate of nanoparticles, including their pharmacokinetics, biodistribution, and therapeutic efficacy. It is progressively being accepted that even slight variations in the composition of a protein source (e...
February 28, 2017: Biomaterials Science
Jinjun Shi, Philip W Kantoff, Richard Wooster, Omid C Farokhzad
The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization...
2017: Nature Reviews. Cancer
Nazila Kamaly, John C He, Dennis A Ausiello, Omid C Farokhzad
Treatment and management of kidney disease currently presents an enormous global burden, and the application of nanotechnology principles to renal disease therapy, although still at an early stage, has profound transformative potential. The increasing translation of nanomedicines to the clinic, alongside research efforts in tissue regeneration and organ-on-a-chip investigations, are likely to provide novel solutions to treat kidney diseases. Our understanding of renal anatomy and of how the biological and physico-chemical properties of nanomedicines (the combination of a nanocarrier and a drug) influence their interactions with renal tissues has improved dramatically...
December 2016: Nature Reviews. Nephrology
Phei Er Saw, Jinho Park, Sangyong Jon, Omid C Farokhzad
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...
October 19, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
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
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