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Targeted Nanoparticles Assembled via Complexation of Boronic-Acid-Containing Targeting Moieties to Diol-Containing Polymers

Han, Han and Davis, Mark E. (2013) Targeted Nanoparticles Assembled via Complexation of Boronic-Acid-Containing Targeting Moieties to Diol-Containing Polymers. Bioconjugate Chemistry, 24 (4). pp. 669-677. ISSN 1043-1802. PMCID PMC3656490. doi:10.1021/bc300640j. https://resolver.caltech.edu/CaltechAUTHORS:20130523-162341580

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Abstract

The delivery of therapeutics via nanoscaled vehicles for solid cancer treatment can be enhanced by the incorporation of a targeting capability. Here, we describe a new method for assembling a targeted nanoparticle that utilizes the reversible covalent complexation between boronic acids and diols to achieve a targeted nanoparticle for the delivery of the anticancer drug camptothecin (CPT). CPT is conjugated to a biocompatible, hydrophilic copolymer of mucic acid and PEG (MAP). When this polymer–drug conjugate is placed in water, it self-assembles into MAP–CPT nanoparticles of ca. 30 nm (diameter) and slightly negative zeta potential. The antibody Herceptin is attached to a boronic acid via a polyethylene glycol (PEG) spacer, and this boronic acid-containing targeting moiety is complexed with the diol-containing MAP to form a targeted MAP–CPT nanoparticle. The addition of Herceptin targeting agent to the MAP–CPT nanoparticles yields targeted MAP–CPT nanoparticles with increased nanoparticle size to ca. 40 nm (diameter). The main mechanisms of CPT release from MAP–CPT nanoparticles are found by in vitro analysis to be hydrolysis and nanoparticle disruption by fat. Cellular uptake of nanoparticles is enhanced by 70% compared to nontargeted version by the incorporation of a single Herceptin antibody targeting agent per nanoparticle. This single Herceptin antibody targeted MAP–CPT nanoparticle system carries ca. 60 CPT molecules per nanoparticle and shows prolonged plasma circulation with an elimination half-life of 21.2 h and AUC value of 2766 μg.h/mL at a 10 mg CPT/kg tail vein injection in mice.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/bc300640jDOIArticle
http://pubs.acs.org/doi/abs/10.1021/bc300640jPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656490PubMed CentralArticle
ORCID:
AuthorORCID
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2013 American Chemical Society. Received: December 4, 2012; Revised: March 1, 2013; Published: March 6, 2013. Published In Issue April 17, 2013. We thank Alasdair McDowall, David VanderVelde, and Leonard Medrano for assistance with cryo-EM imaging, NMR spectroscopy, and cell culture preparation respectively. This project was financially supported by the National Cancer Institute Grant CA 151819.
Funders:
Funding AgencyGrant Number
NIHCA 151819
National Cancer InstituteUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC3656490
DOI:10.1021/bc300640j
Record Number:CaltechAUTHORS:20130523-162341580
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130523-162341580
Official Citation:Targeted Nanoparticles Assembled via Complexation of Boronic-Acid-Containing Targeting Moieties to Diol-Containing Polymers Han Han and Mark E. Davis Bioconjugate Chemistry 2013 24 (4), 669-677
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:38663
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:24 May 2013 15:18
Last Modified:09 Nov 2021 23:39

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