Evaluation of doxorubicin-loaded 3-helix micelles as nanocarriers.
Designing stable drug nanocarriers, 10-30 nm in size, would have significant impact on their transport in circulation, tumor penetration, and therapeutic efficacy. In the present study, biological properties of 3-helix micelles loaded with 8 wt % doxorubicin (DOX), ~15 nm in size, were characterized to validate their potential as a nanocarrier platform. DOX-loaded micelles exhibited high stability in terms of size and drug retention in concentrated protein environments similar to conditions after intravenous injections. DOX-loaded micelles were cytotoxic to PPC-1 and 4T1 cancer cells at levels comparable to free DOX. 3-Helix micelles can be disassembled by proteolytic degradation of peptide shell to enable drug release and clearance to minimize long-term accumulation. Local administration to normal rat striatum by convection enhanced delivery (CED) showed greater extent of drug distribution and reduced toxicity relative to free drug. Intravenous administration of DOX-loaded 3-helix micelles demonstrated improved tumor half-life and reduced toxicity to healthy tissues in comparison to free DOX. In vivo delivery of DOX-loaded 3-helix micelles through two different routes clearly indicates the potential of 3-helix micelles as safe and effective nanocarriers for cancer therapeutics.
Department of Materials Science and Engineering, University of California , Berkeley, California 94720, United States.
Nikhil
N
Dube
Jessica Y
JY
Shu
He
H
Dong
Jai W
JW
Seo
Elizabeth
E
Ingham
Azadeh
A
Kheirolomoom
Pin-Yuan
PY
Chen
John
J
Forsayeth
Krystof
K
Bankiewicz
Katherine W
KW
Ferrara
Ting
T
Xu
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008822:Mice, Transgenic; D008823:Micelles; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013499:Surface Properties
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D004317:Doxorubicin