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https://www.readbyqxmd.com/read/28974673/mechanistic-understanding-of-in-vivo-protein-corona-formation-on-polymeric-nanoparticles-and-impact-on-pharmacokinetics
#1
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 nm(2) prolong circulation times, irrespective of size...
October 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28918266/nanomedicine-for-safe-healing-of-bone-trauma-opportunities-and-challenges
#2
REVIEW
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
https://www.readbyqxmd.com/read/28875984/multiscale-technologies-for-treatment-of-ischemic-cardiomyopathy
#3
REVIEW
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
https://www.readbyqxmd.com/read/28730752/targeted-nanotherapeutics-encapsulating-liver-x-receptor-agonist-gw3965-enhance-antiatherogenic-effects-without-adverse-effects-on-hepatic-lipid-metabolism-in-ldlr-mice
#4
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...
July 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28681981/ros-responsive-polyprodrug-nanoparticles-for-triggered-drug-delivery-and-effective-cancer-therapy
#5
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
https://www.readbyqxmd.com/read/28661127/challenges-in-dna-delivery-and-recent-advances-in-multifunctional-polymeric-dna-delivery-systems
#6
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...
July 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28638484/surface-de-pegylation-controls-nanoparticle-mediated-sirna-delivery-in-vitro-and-in-vivo
#7
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
https://www.readbyqxmd.com/read/28636389/tumor-microenvironment-responsive-multistaged-nanoplatform-for-systemic-rnai-and-cancer-therapy
#8
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
https://www.readbyqxmd.com/read/28585944/cellular-uptake-of-nanoparticles-journey-inside-the-cell
#9
REVIEW
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
https://www.readbyqxmd.com/read/28323414/design-of-insulin-loaded-nanoparticles-enabled-by-multistep-control-of-nanoprecipitation-and-zinc-chelation
#10
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
https://www.readbyqxmd.com/read/28240870/multifunctional-envelope-type-sirna-delivery-nanoparticle-platform-for-prostate-cancer-therapy
#11
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
https://www.readbyqxmd.com/read/28199099/nanoscience-and-nanotechnology-cross-borders
#12
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
https://www.readbyqxmd.com/read/28167390/hyper-cell-permeable-micelles-as-a-drug-delivery-carrier-for-effective-cancer-therapy
#13
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
https://www.readbyqxmd.com/read/28133653/personalized-protein-corona-on-nanoparticles-and-its-clinical-implications
#14
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
https://www.readbyqxmd.com/read/27834398/cancer-nanomedicine-progress-challenges-and-opportunities
#15
REVIEW
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...
January 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27795549/nanomedicines-for-renal-disease-current-status-and-future-applications
#16
REVIEW
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
https://www.readbyqxmd.com/read/27769887/a-drug-delivery-strategy-for-overcoming-drug-resistance-in-breast-cancer-through-targeting-of-oncofetal-fibronectin
#17
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...
February 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27663778/biological-identity-of-nanoparticles-in-vivo-clinical-implications-of-the-protein-corona
#18
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
https://www.readbyqxmd.com/read/27529192/targeted-nanoparticles-for-colorectal-cancer
#19
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
https://www.readbyqxmd.com/read/27342857/theranostic-near-infrared-fluorescent-nanoplatform-for-imaging-and-systemic-sirna-delivery-to-metastatic-anaplastic-thyroid-cancer
#20
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
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