期刊
ACS NANO
卷 6, 期 6, 页码 5320-5329出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn301142r
关键词
3-helix micelle; peptide-polymer conjugate; helix bundle; nanocarriers; stability
类别
资金
- Office of Army of the U.S. Department of Defense [W91NF-09-1-0374]
- Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]
- NIH [R01CA103828-6]
- National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268201000043C]
Generating stable, multifunctional organic nanocarriers will have a significant impact on drug formulation. However, it remains a significant challenge to generate organic nanocarriers with a long circulation half-life, effective tumor penetration, and efficient clearance of metabolites. We have advanced this goal by designing a new family of amphiphiles based on coiled-coil 3-helix bundle forming peptide poly(ethylene glycol) conjugates. The amphiphiles self-assemble into monodisperse micellar nanoparticles, 15 nm in diameter. Using the 3-helix micelles, a drug loading of similar to 8 wt % was obtained using doxorubicin and the micelles showed minimal cargo leakage after 12 h of incubation with serum proteins at 37 degrees C. In vivo pharmacokinetics studies using positron emission tomography showed a circulation half-life of 29.5 h and minimal accumulation in the liver and spleen. The demonstrated strategy, by incorporating unique protein tertiary structure in the headgroup of an amphiphile, opens new avenues to generate organic nanoparticles with tunable stability, ligand clustering, and controlled disassembly to meet current demands in nanomedicine.
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