Effective treatment of cancer metastasis using a dual-ligand nanoparticle

• Published in: PloS one Vol. 14; no. 7; p. e0220474
• Main Authors: Covarrubias, Gil, He, Felicia, Raghunathan, Shruti, Turan, Oguz, Peiris, Pubudu M, Schiemann, William P, Karathanasis, Efstathios
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.07.2019; Public Library of Science (PLoS)
• Subjects: Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Anticancer properties; Biology and Life Sciences; Biomedical engineering; Biomedical materials; Brain cancer; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer cells; Cancer metastasis; Cancer therapies; Care and treatment; Chemical properties; Chemotherapy; Control; Cytotoxicity; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Endothelium; Engineering; Engineering and Technology; Epidermal growth factor receptors; ErbB Receptors - chemistry; ErbB Receptors - metabolism; Female; Growth; Growth factors; Heterogeneity; Humans; Integrin alphaVbeta3 - chemistry; Integrin alphaVbeta3 - metabolism; Ligands; Ligands (Biochemistry); Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Medicine and Health Sciences; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Patient outcomes; Peptides; Receptors; Research and Analysis Methods; Survival; Topology; Treatment Outcome; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays; United States > US; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0220474

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 αvβ3 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 αvβ3 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, αvβ3 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.