PMID- 31356633

OWN - NLM
STAT- In-Data-Review
LR - 20190729
IS - 1932-6203 (Electronic)
IS - 1932-6203 (Linking)
VI - 14
IP - 7
DP - 2019
TI - Effective treatment of cancer metastasis using a dual-ligand nanoparticle.
PG - e0220474
LID - 10.1371/journal.pone.0220474 [doi]
AB - 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 alphavbeta3 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
alphavbeta3 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, alphavbeta3 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.
FAU - Covarrubias, Gil
AU - Covarrubias G
AD - Department of Biomedical Engineering, Case Western Reserve University,
Cleveland,
Ohio, United States of America.
FAU - He, Felicia
AU - He F
AD - Department of Biomedical Engineering, Case Western Reserve University,
Cleveland,
Ohio, United States of America.
FAU - Raghunathan, Shruti
AU - Raghunathan S
AD - Department of Biomedical Engineering, Case Western Reserve University,
Cleveland,
Ohio, United States of America.
FAU - Turan, Oguz
AU - Turan O
AD - Department of Biomedical Engineering, Case Western Reserve University,
Cleveland,
Ohio, United States of America.
FAU - Peiris, Pubudu M
AU - Peiris PM
AD - Department of Biomedical Engineering, Case Western Reserve University,
Cleveland,
Ohio, United States of America.
FAU - Schiemann, William P
AU - Schiemann WP
AD - Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland,
Ohio, United States of America.
FAU - Karathanasis, Efstathios
AU - Karathanasis E
AUID- ORCID: http://orcid.org/0000-0001-7484-7552
AD - Department of Biomedical Engineering, Case Western Reserve University,
Cleveland,
Ohio, United States of America.
AD - Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland,
Ohio, United States of America.
LA - eng
PT - Journal Article
DEP - 20190729
PL - United States
TA - PLoS One
JT - PloS one
JID - 101285081
SB - IM
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/07/30 06:00
MHDA- 2019/07/30 06:00
CRDT- 2019/07/30 06:00
PHST- 2019/04/17 00:00 [received]
PHST- 2019/07/16 00:00 [accepted]
PHST- 2019/07/30 06:00 [entrez]
PHST- 2019/07/30 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
AID - 10.1371/journal.pone.0220474 [doi]
AID - PONE-D-19-11014 [pii]
PST - epublish
SO - PLoS One. 2019 Jul 29;14(7):e0220474. doi: 10.1371/journal.pone.0220474.
eCollection 2019.