On-command drug release from nanochains inhibits growth of breast tumors.
OBJECTIVE
To evaluate the ability of radiofrequency (RF)-triggered drug release from a multicomponent chain-shaped nanoparticle to inhibit the growth of an aggressive breast tumor.


METHODS
A two-step solid phase chemistry was employed to synthesize doxorubicin-loaded nanochains, which were composed of three iron oxide nanospheres and one doxorubicin-loaded liposome assembled in a 100-nm-long linear nanochain. The nanochains were tested in the 4T1-LUC-GFP orthotopic mouse model, which is a highly aggressive breast cancer model. The 4T1-LUC-GFP cell line stably expresses firefly luciferase, which allowed the non-invasive in vivo imaging of tumor response to the treatment using bioluminescence imaging (BLI).


RESULTS
Longitudinal BLI imaging showed that a single nanochain treatment followed by application of RF resulted in an at least 100-fold lower BLI signal compared to the groups treated with nanochains (without RF) or free doxorubicin followed by RF. A statistically significant increase in survival time of the nanochain-treated animals followed by RF (64.3 days) was observed when compared to the nanochain-treated group without RF (35.7 days), free doxorubicin-treated group followed by RF (38.5 days), and the untreated group (30.5 days; n=5 animals per group).


CONCLUSIONS
These studies showed that the combination of RF and nanochains has the potential to effectively treat highly aggressive cancers and prolong survival.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
Pubudu M
PM
Peiris
Morgan
M
Tam
Peter
P
Vicente
Aaron
A
Abramowski
Randall
R
Toy
Lisa
L
Bauer
Aaron
A
Mayer
Jenna
J
Pansky
Elizabeth
E
Doolittle
Samantha
S
Tucci
Erik
E
Schmidt
Christopher
C
Shoup
Swetha
S
Rao
Kaitlyn
K
Murray
Ramamurthy
R
Gopalakrishnan
Ruth A
RA
Keri
James P
JP
Basilion
Mark A
MA
Griswold
Efstathios
E
Karathanasis
D000277:Adjuvants, Pharmaceutic; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D049449:Luminescence; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011846:Radio Waves; D016019:Survival Analysis; D047368:Tumor Burden
D000277:Adjuvants, Pharmaceutic; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin