Serum biomarkers for personalization of nanotherapeutics-based therapy in different tumor and organ microenvironments

Kenji Yokoi; Tomonori Tanei; Biana Godin; Anne L van de Ven; Masaki Hanibuchi; Aika Matsunoki; Jenolyn Alexander; Mauro Ferrari

doi:10.1016/j.canlet.2013.11.015

Serum biomarkers for personalization of nanotherapeutics-based therapy in different tumor and organ microenvironments

Cancer Lett. 2014 Apr 1;345(1):48-55. doi: 10.1016/j.canlet.2013.11.015. Epub 2013 Dec 24.

Authors

Kenji Yokoi¹, Tomonori Tanei², Biana Godin², Anne L van de Ven², Masaki Hanibuchi³, Aika Matsunoki³, Jenolyn Alexander², Mauro Ferrari⁴

Affiliations

¹ Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, Houston, TX 77030, USA; Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: [email protected].
² Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, Houston, TX 77030, USA.
³ Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
⁴ Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, Houston, TX 77030, USA. Electronic address: [email protected].

Abstract

Enhanced permeation and retention (EPR) effect, the mechanism by which nanotherapeutics accumulate in tumors, varies in patients based on differences in the tumor and organ microenvironment. Surrogate biomarkers for the EPR effect will aid in selecting patients who will accumulate higher amounts of nanotherapeutics and show better therapeutic efficacy. Our data suggest that the differences in the vascular permeability and pegylated liposomal doxorubicin (PLD) accumulation are tumor type as well as organ-specific and significantly correlated with the relative ratio of MMP-9 to TIMP-1 in the circulation, supporting development of these molecules as biomarkers for the personalization of nanoparticle-based therapy.

Keywords: Biomarker; EPR effect; Nanotherapeutics; PLD; Transport oncophysics.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibiotics, Antineoplastic / administration & dosage
Antibiotics, Antineoplastic / pharmacokinetics
Biomarkers, Tumor / blood*
Brain Neoplasms / blood
Brain Neoplasms / drug therapy
Brain Neoplasms / metabolism
Brain Neoplasms / secondary
Capillary Permeability
Doxorubicin / administration & dosage
Doxorubicin / analogs & derivatives*
Doxorubicin / pharmacokinetics
Drug Delivery Systems
Female
Liver Neoplasms, Experimental / blood
Liver Neoplasms, Experimental / drug therapy
Liver Neoplasms, Experimental / metabolism
Matrix Metalloproteinase 9 / blood
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Nude
Nanoparticles / administration & dosage
Nanoparticles / metabolism
Neoplasms, Experimental / blood*
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / pathology
Polyethylene Glycols / administration & dosage
Polyethylene Glycols / pharmacokinetics
Tissue Inhibitor of Metalloproteinase-1 / blood
Tumor Microenvironment
Xenograft Model Antitumor Assays

Substances

Antibiotics, Antineoplastic
Biomarkers, Tumor
Tissue Inhibitor of Metalloproteinase-1
liposomal doxorubicin
Polyethylene Glycols
Doxorubicin
Matrix Metalloproteinase 9

Grants and funding

U54 CA143837/CA/NCI NIH HHS/United States