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An injectable nanoparticle generator enhances delivery of cancer therapeutics

The efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particl... Full description

Journal Title: Nature biotechnology 2016, Vol.34 (4), p.414-418
Main Author: Xu, Rong
Other Authors: Zhang, Guodong , Mai, Junhua , Deng, Xiaoyong , Segura-Ibarra, Victor , Wu, Suhong , Shen, Jianliang , Liu, Haoran , Hu, Zhenhua , Chen, Lingxiao , Huang, Yi , Koay, Eugene , Huang, Yu , Liu, Jun , Ensor, Joe E , Blanco, Elvin , Liu, Xuewu , Ferrari, Mauro , Shen, Haifa
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1087-0156
Link: https://www.ncbi.nlm.nih.gov/pubmed/26974511
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title: An injectable nanoparticle generator enhances delivery of cancer therapeutics
format: Article
creator:
  • Xu, Rong
  • Zhang, Guodong
  • Mai, Junhua
  • Deng, Xiaoyong
  • Segura-Ibarra, Victor
  • Wu, Suhong
  • Shen, Jianliang
  • Liu, Haoran
  • Hu, Zhenhua
  • Chen, Lingxiao
  • Huang, Yi
  • Koay, Eugene
  • Huang, Yu
  • Liu, Jun
  • Ensor, Joe E
  • Blanco, Elvin
  • Liu, Xuewu
  • Ferrari, Mauro
  • Shen, Haifa
subjects:
  • Animals
  • Antineoplastic Agents - administration & dosage
  • Antineoplastic Agents - pharmacokinetics
  • Antineoplastic Agents - therapeutic use
  • Article
  • Cancer
  • Cancer therapies
  • Cell Line, Tumor
  • Doxorubicin - administration & dosage
  • Doxorubicin - pharmacokinetics
  • Doxorubicin - therapeutic use
  • Drug Delivery Systems - methods
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Nanomedicine - methods
  • Nanoparticles
  • Nanoparticles - administration & dosage
  • Nanoparticles - therapeutic use
  • Neoplasms - drug therapy
  • Polyglutamic Acid
  • Tumors
  • Xenograft Model Antitumor Assays
ispartof: Nature biotechnology, 2016, Vol.34 (4), p.414-418
description: The efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(L-glutamic acid) by means of a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40-50% of treated mice.
language: eng
source:
identifier: ISSN: 1087-0156
fulltext: no_fulltext
issn:
  • 1087-0156
  • 1546-1696
url: Link


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descriptionThe efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(L-glutamic acid) by means of a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40-50% of treated mice.
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descriptionThe efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(L-glutamic acid) by means of a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40-50% of treated mice.
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0These authors contributed equally to this work.
1Current address: Biomedical Engineering Department, University of South Dakota, Sioux Falls, South Dakota, USA
2Current address: Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai, China
abstractThe efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(L-glutamic acid) by means of a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40-50% of treated mice.
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