Open AccessEffective treatment of cancer metastasis using a dual-ligand nanoparticle
Author(s) -
Gil Covarrubias,
Felicia He,
Shruti Raghunathan,
Oguz Turan,
Pubudu M. Peiris,
William P. Schiemann,
Efstathios Karathanasis
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0220474
Subject(s) - metastasis , breast cancer , cancer research , cancer , in vivo , metastatic breast cancer , cancer cell , medicine , tumor microenvironment , doxorubicin , biology , chemotherapy , microbiology and biotechnology
Metastasis is responsible for the majority of deaths of breast cancer patients. While cytotoxic drugs are available with high potency to kill breast cancer cells, they are not designed to specifically seek and navigate in the dynamic and continuously changing microenvironment of metastatic disease. To effectively delivery chemotherapeutic agents to metastasis, we designed a dual-ligand nanoparticle loaded with doxorubicin by using two different types of ligands targeting EGFR and α v β 3 integrin. Metastatic cancer cells continuously change resulting in heterogeneity even across adjacent micrometastatic regions with variable expression of these targetable receptors. Using a mouse model of breast cancer metastasis, in vivo and ex vivo imaging showed that both EGFR and α v β 3 integrin-targeting were required to reliably direct the nanoparticle to metastasis and capture the spread and exact topology of the disease. Survival studies compared the anticancer efficacy of the standard drug, EGFR-targeting nanoparticle, α v β 3 integrin-targeting nanoparticle and the dual-ligand nanoparticle. While all the other treatments produced moderate therapeutic outcomes, treatment with the dual-ligand nanoparticle yielded significant improvement and event-free survival in a mouse model of breast cancer metastasis.