Cargando…

Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery

Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Emmy, Qian, Weiping, Cao, Zehong, Wang, Liya, Bozeman, Erica N., Ward, Christina, Yang, Bin, Selvaraj, Periasamy, Lipowska, Malgorzata, Wang, Y. Andrew, Mao, Hui, Yang, Lily
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265747/
https://www.ncbi.nlm.nih.gov/pubmed/25553097
http://dx.doi.org/10.7150/thno.10350
_version_ 1782348933907873792
author Yang, Emmy
Qian, Weiping
Cao, Zehong
Wang, Liya
Bozeman, Erica N.
Ward, Christina
Yang, Bin
Selvaraj, Periasamy
Lipowska, Malgorzata
Wang, Y. Andrew
Mao, Hui
Yang, Lily
author_facet Yang, Emmy
Qian, Weiping
Cao, Zehong
Wang, Liya
Bozeman, Erica N.
Ward, Christina
Yang, Bin
Selvaraj, Periasamy
Lipowska, Malgorzata
Wang, Y. Andrew
Mao, Hui
Yang, Lily
author_sort Yang, Emmy
collection PubMed
description Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers.
format Online
Article
Text
id pubmed-4265747
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-42657472015-01-01 Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery Yang, Emmy Qian, Weiping Cao, Zehong Wang, Liya Bozeman, Erica N. Ward, Christina Yang, Bin Selvaraj, Periasamy Lipowska, Malgorzata Wang, Y. Andrew Mao, Hui Yang, Lily Theranostics Research Paper Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers. Ivyspring International Publisher 2015-01-01 /pmc/articles/PMC4265747/ /pubmed/25553097 http://dx.doi.org/10.7150/thno.10350 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
spellingShingle Research Paper
Yang, Emmy
Qian, Weiping
Cao, Zehong
Wang, Liya
Bozeman, Erica N.
Ward, Christina
Yang, Bin
Selvaraj, Periasamy
Lipowska, Malgorzata
Wang, Y. Andrew
Mao, Hui
Yang, Lily
Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery
title Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery
title_full Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery
title_fullStr Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery
title_full_unstemmed Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery
title_short Theranostic Nanoparticles Carrying Doxorubicin Attenuate Targeting Ligand Specific Antibody Responses Following Systemic Delivery
title_sort theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265747/
https://www.ncbi.nlm.nih.gov/pubmed/25553097
http://dx.doi.org/10.7150/thno.10350
work_keys_str_mv AT yangemmy theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT qianweiping theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT caozehong theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT wangliya theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT bozemanerican theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT wardchristina theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT yangbin theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT selvarajperiasamy theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT lipowskamalgorzata theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT wangyandrew theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT maohui theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery
AT yanglily theranosticnanoparticlescarryingdoxorubicinattenuatetargetingligandspecificantibodyresponsesfollowingsystemicdelivery