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Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles (NPs) that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as "foreign", resulting in their clearance by the mononuclear phagocytic system (MPS). To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories: synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall, bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery, and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.


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Advances in targeted nanotherapeutics: From bioconjugation to biomimicry

Show Author's information Danielle M. Valcourt1Jenna Harris2Rachel S. Riley1Megan Dang1Jianxin Wang1Emily S. Day1,2,3( )
161 Colburn LabDepartment of Biomedical EngineeringUniversity of DelawareNewarkDE19716USA
201 DuPont HallDepartment of Materials Science & EngineeringUniversity of DelawareNewarkDE19716USA
4701 Ogletown Stanton RoadHelen F. Graham Cancer Center & Research InstituteNewarkDE19713USA

Abstract

Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles (NPs) that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as "foreign", resulting in their clearance by the mononuclear phagocytic system (MPS). To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories: synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall, bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery, and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.

Keywords: nanoparticles, cancer, targeting, biomimicry, bioconjugation, delivery

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Publication history
Copyright
Acknowledgements

Publication history

Received: 14 March 2018
Revised: 25 April 2018
Accepted: 26 April 2018
Published: 17 May 2018
Issue date: October 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Acknowledgements

Acknowledgements

This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM119659, and by a grant from the W.M. Keck Foundation. R. S. R. received support from an American Association of University Women Dissertation Fellowship. The content is solely the responsibility of the authors and does not necessarily reflect the views of the funding agencies.

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