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Engineering nanoparticles to overcome barriers to immunotherapy

Advances in immunotherapy have led to the development of a variety of promising therapeutics, including small molecules, proteins and peptides, monoclonal antibodies, and cellular therapies. Despite this wealth of new therapeutics, the efficacy of immunotherapy has been limited by challenges in targ...

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Detalles Bibliográficos
Autores principales: Toy, Randall, Roy, Krishnendu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689503/
https://www.ncbi.nlm.nih.gov/pubmed/29313006
http://dx.doi.org/10.1002/btm2.10005
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author Toy, Randall
Roy, Krishnendu
author_facet Toy, Randall
Roy, Krishnendu
author_sort Toy, Randall
collection PubMed
description Advances in immunotherapy have led to the development of a variety of promising therapeutics, including small molecules, proteins and peptides, monoclonal antibodies, and cellular therapies. Despite this wealth of new therapeutics, the efficacy of immunotherapy has been limited by challenges in targeted delivery and controlled release, that is, spatial and temporal control on delivery. Particulate carriers, especially nanoparticles have been widely studied in drug delivery and vaccine research and are being increasingly investigated as vehicles to deliver immunotherapies. Nanoparticle‐mediated drug delivery could provide several benefits, including control of biodistribution and transport kinetics, the potential for site‐specific targeting, immunogenicity, tracking capability using medical imaging, and multitherapeutic loading. There are also a unique set of challenges, which include nonspecific uptake by phagocytic cells, off‐target biodistribution, permeation through tissue (transport limitation), nonspecific immune‐activation, and poor control over intracellular localization. This review highlights the importance of understanding the relationship between a nanoparticle's size, shape, charge, ligand density and elasticity to its vascular transport, biodistribution, cellular internalization, and immunogenicity. For the design of an effective immunotherapy, we highlight the importance of selecting a nanoparticle's physical characteristics (e.g., size, shape, elasticity) and its surface functionalization (e.g., chemical or polymer modifications, targeting or tissue‐penetrating peptides) with consideration of its reactivity to the targeted microenvironment (e.g., targeted cell types, use of stimuli‐sensitive biomaterials, immunogenicity). Applications of this rational nanoparticle design process in vaccine development and cancer immunotherapy are discussed.
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spelling pubmed-56895032018-01-08 Engineering nanoparticles to overcome barriers to immunotherapy Toy, Randall Roy, Krishnendu Bioeng Transl Med Reviews Advances in immunotherapy have led to the development of a variety of promising therapeutics, including small molecules, proteins and peptides, monoclonal antibodies, and cellular therapies. Despite this wealth of new therapeutics, the efficacy of immunotherapy has been limited by challenges in targeted delivery and controlled release, that is, spatial and temporal control on delivery. Particulate carriers, especially nanoparticles have been widely studied in drug delivery and vaccine research and are being increasingly investigated as vehicles to deliver immunotherapies. Nanoparticle‐mediated drug delivery could provide several benefits, including control of biodistribution and transport kinetics, the potential for site‐specific targeting, immunogenicity, tracking capability using medical imaging, and multitherapeutic loading. There are also a unique set of challenges, which include nonspecific uptake by phagocytic cells, off‐target biodistribution, permeation through tissue (transport limitation), nonspecific immune‐activation, and poor control over intracellular localization. This review highlights the importance of understanding the relationship between a nanoparticle's size, shape, charge, ligand density and elasticity to its vascular transport, biodistribution, cellular internalization, and immunogenicity. For the design of an effective immunotherapy, we highlight the importance of selecting a nanoparticle's physical characteristics (e.g., size, shape, elasticity) and its surface functionalization (e.g., chemical or polymer modifications, targeting or tissue‐penetrating peptides) with consideration of its reactivity to the targeted microenvironment (e.g., targeted cell types, use of stimuli‐sensitive biomaterials, immunogenicity). Applications of this rational nanoparticle design process in vaccine development and cancer immunotherapy are discussed. John Wiley and Sons Inc. 2016-06-20 /pmc/articles/PMC5689503/ /pubmed/29313006 http://dx.doi.org/10.1002/btm2.10005 Text en © 2016 The Authors. Bioengineering & Translational Medicine is published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Toy, Randall
Roy, Krishnendu
Engineering nanoparticles to overcome barriers to immunotherapy
title Engineering nanoparticles to overcome barriers to immunotherapy
title_full Engineering nanoparticles to overcome barriers to immunotherapy
title_fullStr Engineering nanoparticles to overcome barriers to immunotherapy
title_full_unstemmed Engineering nanoparticles to overcome barriers to immunotherapy
title_short Engineering nanoparticles to overcome barriers to immunotherapy
title_sort engineering nanoparticles to overcome barriers to immunotherapy
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689503/
https://www.ncbi.nlm.nih.gov/pubmed/29313006
http://dx.doi.org/10.1002/btm2.10005
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