Computational design of nanoparticle drug delivery systems for selective targeting

Nanoscale
Gregg A Duncan, Michael A Bevan

Abstract

Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.

References

Apr 1, 1996·Current Opinion in Immunology·P A van der Merwe, A N Barclay
Jun 19, 2001·The Journal of Biological Chemistry·M K WildD Vestweber
Dec 18, 2002·Critical Reviews in Clinical Laboratory Sciences·David NaorYoram Faitelson
May 21, 2004·The New England Journal of Medicine·Nancy J Olsen, C Michael Stein
Jan 21, 2006·Nature Reviews. Drug Discovery·David SchramaJürgen C Becker
Feb 24, 2006·Nature Reviews. Cancer·Jonathan M IrishGarry P Nolan
Feb 13, 2007·Nature Structural & Molecular Biology·Suneale BanerjiDavid G Jackson
Nov 16, 2007·Langmuir : the ACS Journal of Surfaces and Colloids·Cheng-Zhong Zhang, Zhen-Gang Wang
Jan 25, 2008·Journal of Cell Science·Maddy ParsonsMartin J Humphries
Feb 1, 2008·American Journal of Physiology. Cell Physiology·Christina S AlvesKonstantinos Konstantopoulos
Jul 18, 2008·Langmuir : the ACS Journal of Surfaces and Colloids·Jered B Haun, Daniel A Hammer
Aug 21, 2008·Current Neurology and Neuroscience Reports·John W RoseNoel Carlson
Oct 7, 2008·Langmuir : the ACS Journal of Surfaces and Colloids·Matthew C HagyElena E Dormidontova
May 16, 2009·Proceedings of the National Academy of Sciences of the United States of America·Saumyadipta PyneJill P Mesirov
Sep 29, 2009·Biomaterials·Ki Young ChoiSeo Young Jeong
Jun 12, 2010·Biomacromolecules·Shihu Wang, Elena E Dormidontova
Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jin LiuRavi Radhakrishnan
Mar 26, 2011·Bioconjugate Chemistry·Daniela ArosioCarlo Scolastico
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Francisco J Martinez-Veracoechea, Daan Frenkel
Oct 5, 2011·ACS Nano·Ki Young ChoiJae Hyung Park
Oct 6, 2011·Molecular Cancer Research : MCR·Jeanne M V Louderbough, Joyce A Schroeder
Nov 4, 2011·Nano Letters·Robert VáchaDaan Frenkel
Oct 10, 2012·Annual Review of Medicine·Eric L Sievers, Peter D Senter
Apr 27, 2013·Scientific Reports·UNKNOWN Physical Sciences - Oncology Centers NetworkPei-Hsun Wu
Sep 25, 2014·Soft Matter·Gregg A Duncan, Michael A Bevan

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Citations

Jan 13, 2016·Annals of Surgery·Courtney E MorganMelina R Kibbe
Jul 12, 2016·Journal of Nanomaterials·Xiaojiao YuZi Chen
Oct 28, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Gregg A DuncanMichael A Bevan
May 26, 2017·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Rahim Ghadari, Ashkan Kashefi
Jan 30, 2018·Khirurgiia·Sh V TimerbulatovM V Timerbulatov
Apr 27, 2019·Environmental Science and Pollution Research International·Neha SharmaSalman Akhtar
Jun 1, 2018·Scientific Reports·Nolan C WorstellHung-Jen Wu
Jan 8, 2021·Nanoscale·Bernabé Ortega-Tenezaca, Humberto González-Díaz
Jul 23, 2020·Advanced Drug Delivery Reviews·Romain BrusiniPatrick Couvreur
Feb 27, 2018·ACS Chemical Biology·Chayanon NgambenjawongSuzie H Pun
Sep 2, 2021·Proceedings of the National Academy of Sciences of the United States of America·Christine LinneDaniela J Kraft

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