Fabrication of gold nanoparticles for targeted therapy in pancreatic cancer

Patra, Chitta Ranjan; Bhattacharya, Resham; Mukhopadhyay, Debabrata; Mukherjee, Priyabrata

doi:10.1016/j.addr.2009.11.007

Cited by 419 publications

(272 citation statements)

References 228 publications

(223 reference statements)

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“…EGFR | nanoparticle | dynamin | pancreatic cancer N anotechnology provides opportunities for biomedical applications that may improve human health care in the future (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Engineered nanoparticles are evolving as promising candidates for various biological applications due to their tunable biophysical and biochemical properties (14)(15)(16).…”

mentioning

confidence: 99%

Nanoconjugation modulates the trafficking and mechanism of antibody induced receptor endocytosis

Bhattacharyya¹,

Bhattacharya²,

Curley

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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124

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Treatment with monoclonal antibody (mAbs) is a viable therapeutic option in cancer. Recently, these mAbs such as cetuximab, herceptin, etc., have been used as targeting agents to selectively deliver chemotherapeutics to cancerous cells. However, mechanisms of nanoparticles-mAbs interactions with the target cells and its effect on intracellular trafficking and mechanism are currently unknown. In this paper, we demonstrate that the distinct patterning and dynamics of anti-EGFR (epidermal growth factor receptor) antibody cetuximab (C225)-induced EGFR internalization in pancreatic cancer cells with variable receptor expression is altered upon nanoconjugation. Nanoconjugation uniformly enhanced C225-induced EGFR endocytosis in PANC-1, AsPC-1, and MiaPaca-2 cells, influenced its compartmentalization and regulated the involvement of dynamin-2 in the endocytic processes. Receptor endocytosis and its intracellular trafficking were monitored by confocal microscopy and transmission electron microscopy. The role of dynamin-2 in EGFR endocytosis was determined after overexpressing either wild-type dynamin-2 or mutant dynamin-2 in pancreatic cancer cells followed by tracking the receptor-antibody complex internalization by confocal microscopy. Significantly, these findings demonstrate that the nanoconjugation cannot be construed as an innocuous reaction involved in attaching the targeting agent to the nanoparticle, instead it may distinctly alter the cellular processes at the molecular level, at least antibody induced receptor endocytosis. This information is critical for successful design of a nanoparticle-based targeted drug delivery system for future clinical translation.EGFR | nanoparticle | dynamin | pancreatic cancer N anotechnology provides opportunities for biomedical applications that may improve human health care in the future (1-13). Engineered nanoparticles are evolving as promising candidates for various biological applications due to their tunable biophysical and biochemical properties (14-16). However, fundamental studies to understand the mechanism of cell-nanomaterial interactions are still lacking. To advance the successful development of biomedical nanotechnology for clinical use, vivid understanding of such mechanisms is essential.Epidermal growth factor receptor (EGFR) represents a unique target as over expression of EGFR has been implicated in the pathogenesis of many cancers (17, 18). Cetuximab (C225), a monoclonal anti-EGFR antibody, has been approved by the FDA for treatment of colon and head and neck cancers (19). Cetuximab is also in different phases of clinical trials for other cancers (20,21). However, the mechanism and pattern of C225 induced endocytosis of EGFR in pancreatic cancer cells of variable EGFR expression is not fully understood (20,21). Furthermore, the effect of nanoconjugation on the mechanism of C225 induced endocytosis remains to be investigated. Here, we demonstrate the mechanism and endocytic pattern of C225 and gold conjugated-C225 induced internalization of EGFR in pancreatic ...

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mentioning

confidence: 99%

Nanoconjugation modulates the trafficking and mechanism of antibody induced receptor endocytosis

Bhattacharyya¹,

Bhattacharya²,

Curley

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

124

123

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“…Reversibility of Au-NP induced cytoskeletal disruption of dermal fibroblasts has also been confirmed [66]. Still, potential toxicity of Au-NP remains a topic of debate because, although Au has been used as an antirheumatoid arthritis therapeutic for decades and is widely thought to have minimal toxicology, it now features in NP formats being developed for oral insulin [67] and injectable targeted anticancer payloads [68]. Size, shape, and functionalization might alter in vivo biodistribution and this has toxicity implications even for wellestablished materials [69].…”

Section: Hca: Cytotoxicity Of Npsmentioning

confidence: 95%

High-content analysis for drug delivery and nanoparticle applications

Brayden

Cryan

Dawson

et al. 2015

Drug Discovery Today

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Publication information Drug Discovery Today, 20 (8): 942-957Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6636 Publisher's statementThis is the author's version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 20 (8), (2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 26A c c e p t e d M a n u s c r i p t Sally-Ann CryanSally-Ann Cryan has a pharmacy degree and a PhD in pharmaceutics ( Jeremy SimpsonJeremy Simpson carried out his PhD at the University of Warwick, followed postdoctoral work at the Scripps Research Institute in San Diego, and the Imperial Cancer Research Fund in London. After 9 years as a staff member at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany), he was appointed as professor of cell biology at UCD, in 2008. He currently applies high-throughput imaging technologies to study subcellular transport pathways and the internalization routes taken by nanoparticles in cells. He runs the UCD Cell Screening Laboratory and is the author of more than 80 publications.High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents. A brief recap of cytotoxicity assaysIn vitro cell-based assays have long been used to assess the cytotoxic effects of drug exposure [1]. Cells undergoing acute necrosis swell and lose metabolic capacity, thereby losing the capacity to maintain a barrier to the extracellular space and the ability ...

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“…"Nano" means that items measured in nanometers (nm) for example, one nanometer (nm) is equal one billionth, or 10−9, of a meter. The dimensions of biomolecules are similar to nanoparticles, therefore researchers with miscellaneous benefits and qualifications have converged in their attention to work with and recognize properties of the materials on a nanoscale and use that nanoscale in the medicine [71,72]. Nanotechnology and it uses in cancer is the medical science that will confidently proceed to valuable research aspects, progressive drug distribution systems to target site, really works in diagnosis and treat cancerous diseases or healing injured tissues and cells nowadays [73].…”

Section: Cancer Nanotechnology: Definition and Applicationmentioning

confidence: 99%

Liposomes and Nanotechnology in Drug Development: Focus On Pancreatic Cancer

Malik¹,

Jin²,

Raheem³

et al. 2017

JGPLD

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Pancreatic cancer usually has high morbidity and mortality and rests one of the most challenging cancers to treat. 5 years survival rate is less than 6 percent overall for people with pancreatic cancer, because of very late diagnosis and absence of effective treatment. In a western world, pancreatic tumor is the fourth most common cause of death in a western world. The pancreatic tumor needs selective delivery of drugs to target cells, with no side effects is major goals of the recent investigations for the real treatment of the pancreatic tumor. Medication which targets pancreatic tumor cells specially and carriers which deliver medications to specific cells which are quickly dividing, development of these kind drugs is considered as magic for the management of pancreatic cancer. In latest years, liposomes and nanotechnology can show a vital character in the treatment of pancreatic tumor. Liposomes contain multiple characteristics, such as the ability to protect the material from degradation, the capacity for encapsulating many materials and capability for delivering materials intracellularly fusion with plasma membrane. Nanoparticles as a carrier offer a new style of delivery of the medications to target cells of a tumor and allow drugs for the binding to tumor cell membrane, to cytoplasmic and to nuclear receptor sites. It delivers high medication concentrations to specific cells with few side effects to other normal tissues. The general importance of this evaluation is to increase overall understanding of development of the therapeutic nanomedicine for the treatment of pancreatic tumors, agents delivered by nanoliposomes, liposomal nanomedicine in targeting cancer and safety issues.

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Fabrication of gold nanoparticles for targeted therapy in pancreatic cancer

Cited by 419 publications

References 228 publications

Nanoconjugation modulates the trafficking and mechanism of antibody induced receptor endocytosis

Nanoconjugation modulates the trafficking and mechanism of antibody induced receptor endocytosis

High-content analysis for drug delivery and nanoparticle applications

Liposomes and Nanotechnology in Drug Development: Focus On Pancreatic Cancer

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