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Xiang Lin, Xing Chen, Imogen A Riddell, Wei Tao, Junqing Wang, Geoffrey Hollett, Stephen J Lippard, Omid C Farokhzad, Jinjun Shi, Jun Wu
Despite the broad antitumor spectrum of cisplatin, its therapeutic efficacy in cancer treatment is compromised by development of drug resistance in tumor cells and systemic side effects. A close correlation has been drawn between cisplatin resistance in tumor cells and increased levels of intracellular thiol-containing species, especially glutathione (GSH). The construction of a unique nanoparticle (NP) platform composed of poly(disulfide amide) polymers with a high disulfide density for effective delivery of Pt(IV) prodrugs capable of reversing cisplatin resistance through disulfide group-based GSH-scavenging process, as described herein, is a promising route to overcome limitations associated with tumor resistance...
June 14, 2018: Nano Letters
Wolfgang J Parak, Warren W C Chan, Manish Chhowalla, Omid Farokhzad, Sharon Glotzer, Yury Gogotsi, Paula T Hammond, Mark C Hersam, Ali Javey, Cherie R Kagan, Kazunori Kataoka, Ali Khademhosseini, Nicholas A Kotov, Shuit-Tong Lee, Young Hee Lee, Yan Li, Jill Millstone, Paul A Mulvaney, Andre E Nel, Peter J Nordlander, Reginald M Penner, Andrey L Rogach, Raymond E Schaak, Molly M Stevens, Andrew T S Wee, C Grant Willson, Paul S Weiss
No abstract text is available yet for this article.
April 24, 2018: ACS Nano
Meng Zheng, Wei Tao, Yan Zou, Omid C Farokhzad, Bingyang Shi
Small interfering RNA (siRNA)-based gene silencing technology has demonstrated significant potential for treating brain-associated diseases. However, effective and safe systemic delivery of siRNA into the brain remains challenging because of biological barriers such as enzymatic degradation, short circulation lifetime, the blood-brain barrier (BBB), insufficient tissue penetration, cell endocytosis, and cytosolic transport. Nanotechnology offers intriguing potential for addressing these challenges in siRNA brain delivery in conjunction with chemical and biological modification strategies...
May 2018: Trends in Biotechnology
Xianbing Zhu, Xiaoyuan Ji, Na Kong, Yunhan Chen, Morteza Mahmoudi, Xiaoding Xu, Li Ding, Wei Tao, Ting Cai, Yujing Li, Tian Gan, Austin Barrett, Zameer Bharwani, Hongbo Chen, Omid C Farokhzad
Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials ( i. e., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS2 ) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy...
March 27, 2018: ACS Nano
Warren W C Chan, Manish Chhowalla, Omid Farokhzad, Sharon Glotzer, Yury Gogotsi, Jason H Hafner, Paula T Hammond, Mark C Hersam, Ali Javey, Cherie R Kagan, Kazunori Kataoka, Ali Khademhosseini, Nicholas A Kotov, Shuit-Tong Lee, Yan Li, Jill Millstone, Helmuth Möhwald, Paul C Mulvaney, Andre E Nel, Peter J Nordlander, Wolfgang J Parak, Reginald M Penner, Andrey L Rogach, Raymond E Schaak, Molly M Stevens, Andrew T S Wee, C Grant Willson, Laura E Fernandez, Paul S Weiss
No abstract text is available yet for this article.
December 26, 2017: ACS Nano
Junqing Wang, Wei Tao, Xiaoyuan Chen, Omid C Farokhzad, Gang Liu
The confluence of therapeutics and diagnostics based on the advantages of nanotechnology offers significant opportunities for personalized and precision medicine. Intelligent nanotheranostics based on bioresponsive systems have recently emerged and offer the promise of high specificity and efficiency via "on-demand" activation of both therapeutic and diagnostic capabilities.
2017: Theranostics
Nicolas Bertrand, Philippe Grenier, Morteza Mahmoudi, Eliana M Lima, Eric A Appel, Flavio Dormont, Jong-Min Lim, Rohit Karnik, Robert Langer, Omid C Farokhzad
In vitro incubation of nanomaterials with plasma offer insights on biological interactions, but cannot fully explain the in vivo fate of nanomaterials. Here, we use a library of polymer nanoparticles to show how physicochemical characteristics influence blood circulation and early distribution. For particles with different diameters, surface hydrophilicity appears to mediate early clearance. Densities above a critical value of approximately 20 poly(ethylene glycol) chains (MW 5 kDa) per 100 nm2 prolong circulation times, irrespective of size...
October 3, 2017: Nature Communications
Shahed Behzadi, Gaurav A Luther, Mitchel B Harris, Omid C Farokhzad, Morteza Mahmoudi
Historically, high-energy extremity injuries resulting in significant soft-tissue trauma and bone loss were often deemed unsalvageable and treated with primary amputation. With improved soft-tissue coverage and nerve repair techniques, these injuries now present new challenges in limb-salvage surgery. High-energy extremity trauma is pre-disposed to delayed or unpredictable bony healing and high rates of infection, depending on the integrity of the soft-tissue envelope. Furthermore, orthopedic trauma surgeons are often faced with the challenge of stabilizing and repairing large bony defects while promoting an optimal environment to prevent infection and aid bony healing...
November 2017: Biomaterials
Morteza Mahmoudi, Mikyung Yu, Vahid Serpooshan, Joseph C Wu, Robert Langer, Richard T Lee, Jeffrey M Karp, Omid C Farokhzad
The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart's pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease. Here, we outline recent advancements in nanotechnology that could be exploited to overcome the major obstacles in the prevention of and therapy for heart disease...
September 6, 2017: Nature Nanotechnology
Mikyung Yu, Jaume Amengual, Arjun Menon, Nazila Kamaly, Felix Zhou, Xiaoding Xu, Phei Er Saw, Seung-Joo Lee, Kevin Si, Carleena Angelica Ortega, Won Il Choi, In-Hyun Lee, Yazan Bdour, Jinjun Shi, Morteza Mahmoudi, Sangyong Jon, Edward A Fisher, Omid C Farokhzad
The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized...
October 2017: Advanced Healthcare Materials
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Sushant Bhasin, Yanlan Liu, Dana Ayyash, Jonathan Rasmussen, Marc Huo, Jinjun Shi, Omid C Farokhzad
The application of nanoparticles (NPs) to drug delivery has led to the development of novel nanotherapeutics for the treatment of various diseases including cancer. However, clinical use of NP-mediated drug delivery has not always translated into improved survival of cancer patients, in part due to the suboptimal properties of NP platforms, such as premature drug leakage during preparation, storage, or blood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration. Herein, an innovative reactive oxygen species (ROS)-responsive polyprodrug is reported that can self-assemble into stable NPs with high drug loading...
September 2017: Advanced Materials
Bingyang Shi, Meng Zheng, Wei Tao, Roger Chung, Dayong Jin, Dariush Ghaffari, Omid C Farokhzad
After more than 20 years of intensive investigations, gene therapy has become one of the most promising strategies for treating genetic diseases. However, the lack of ideal delivery systems has limited the clinical realization of gene therapy's tremendous potential, especially for DNA-based gene therapy. Over the past decade, considerable advances have been made in the application of polymer-based DNA delivery systems for gene therapy, especially through multifunctional systems. The core concept behind multifunctional polymeric DNA delivery systems is to endow one single DNA carrier, via materials engineering and surface modification, with several active functions, e...
August 14, 2017: Biomacromolecules
Xi Zhu, Wei Tao, Danny Liu, Jun Wu, Zilei Guo, Xiaoyuan Ji, Zameer Bharwani, Lili Zhao, Xiaoping Zhao, Omid C Farokhzad, Jinjun Shi
The present work proposes a unique de-PEGylation strategy for controllable delivery of small interfering RNA (siRNA) using a robust lipid-polymer hybrid nanoparticle (NP) platform. The self-assembled hybrid NPs are composed of a lipid-poly(ethylene glycol) (lipid-PEG) shell and a polymer/cationic lipid solid core, wherein the lipid-PEG molecules can gradually dissociate from NP surface in the presence of serum albumin. The de-PEGylation kinetics of a series of different lipid-PEGs is measured with their respective NPs, and the NP performance is comprehensively investigated in vitro and in vivo ...
2017: Theranostics
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Mikyung Yu, Morteza Mahmoudi, Jonathan Rasmussen, Dana Ayyash, Yuxiao Zhou, Omid C Farokhzad, Jinjun Shi
While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, the effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core...
July 12, 2017: Nano Letters
Shahed Behzadi, Vahid Serpooshan, Wei Tao, Majd A Hamaly, Mahmoud Y Alkawareek, Erik C Dreaden, Dennis Brown, Alaaldin M Alkilany, Omid C Farokhzad, Morteza Mahmoudi
Nanoscale materials are increasingly found in consumer goods, electronics, and pharmaceuticals. While these particles interact with the body in myriad ways, their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. Nanoparticles (NPs) can modulate cell fate, induce or prevent mutations, initiate cell-cell communication, and modulate cell structure in a manner dictated largely by phenomena at the nano-bio interface. Recent advances in chemical synthesis have yielded new nanoscale materials with precisely defined biochemical features, and emerging analytical techniques have shed light on nuanced and context-dependent nano-bio interactions within cells...
July 17, 2017: Chemical Society Reviews
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...
April 5, 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...
April 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
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